asymmetric catalysis, privileged ligands and complexes · asymmetric catalysis privileged ligands...

Asymmetric CatalysisPrivileged Ligands and Complexes

Features include:

BINAP/SEGPHOS®

Ligands and Complexes

Solvias® Ligand Portfolio for Enantioselective Hydrogenation

DuPhos and BPE Phospholane Ligands and Complexes

Vol. 8, No. 2

BINAP, a powerful ligand for asymmetric catalysis

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2

Vol. 8 No. 2

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About Our Cover

IntroductionThe quest for novel, efficient chiral transition metal catalysts has been an ongoing endeavor for the past 40 years. Leading this quest is the need from the pharmaceutical, flavors and fragrances, and agrochemical industries for enantiopure molecules. Nearly 85% of new drugs in the market are chiral. This need has led to developments in asymmetric synthesis of chiral ligands and metal complexes. In 2001, the Nobel Prize rewarded the pioneering work of Knowles, Noyori, and Sharpless in the development of catalytic asymmetric synthesis, highlighting the importance of chiral synthesis in chemistry. The pioneering work of Noyori in the 1980s with BINAP ligands began an era where catalysts and ligands became more effective and selective.

Highly effective asymmetric catalytic systems give access to arrays of chiral building blocks used in the synthesis of natural products and drugs. Among the plethora of chiral ligands, a few stand out because of their versatility. The common feature of these “privileged” ligands is their C2 symmetry, reducing the number of possible isomeric metal complexes and the number of different substrates. Among the most recognized family of chiral ligands, BINAP, salens, bisoxazolines, tartrate ligands, and cinchona alkaloids represent the original “privileged ligands” classes that affect a wide variety of transformations under outstanding enantiocontrol and with high yield. A second wave of privileged ligands has surfaced with the DuPhos phospholanes, DSM phosphoramidites, Solvias Josiphos families, the Reetz and Trost ligands, and ChiralQuest phosphines. These outstanding ligand families have proven their success in industrially useful reactions such as hydrogenations, aldol reactions, and asymmetric allylic alkylations, and gained much attention from the synthetic community due to the ready accessibility and modular nature of their design.

For each of the privileged ligands, representative examples are presented.

At Sigma-Aldrich®, we are committed to providing unprecedented accessibility to chiral, state-of-the-art “privileged ligands” used in a wide variety of C–H, C–C, C–N, and C–O bond-forming transformations. For a complete listing of products related to privileged ligands, please visit sigma-aldrich.com/privileged. If you cannot find a product for your research efforts in organic synthesis or drug discovery, we welcome your input. “Please Bother Us.” with your suggestions at [email protected] or [email protected], or contact your local Sigma-Aldrich office.

The cover graphic represents the three-dimensional structure of BINAP. The phosphorus atoms are represented in blue. This chiral ligand proved to be one of the most popular, for a variety of asymmetric transformations.

Intr

od

uct

ion

William SommerProduct Manager

Daniel WeibelProduct Manager

Table of ContentsBINAP/SEGPHOS® Ligands and Complexes ................................................................................3

Solvias® Ligand Portfolio for Enantioselective Hydrogenation ..................................................14

DuPhos and BPE Phospholane Ligands and Complexes ...........................................................34

catASium®—Essential Elements for Asymmetric Hydrogenations .............................................40

P-Phos, PhanePhos and BoPhoz™ Ligands ...............................................................................44

ChiralQuest Phosphine Ligands and Complexes ......................................................................47

DSM MonoPhos™ Family .........................................................................................................51

Reetz Ligands .........................................................................................................................54

BINOL and Derivatives .............................................................................................................56

TADDOL ..................................................................................................................................62

BOX ........................................................................................................................................64

PYBOX ....................................................................................................................................67

PHOX ......................................................................................................................................69

Salen Ligands ..........................................................................................................................71

Cinchona Alkaloids .................................................................................................................74

QuinoxP* Ligands ...................................................................................................................79

DIPAMP ..................................................................................................................................81

DIOP .......................................................................................................................................81

Trost Ligands ...........................................................................................................................82

Landis Ligands ........................................................................................................................84

Aminophosphine Ligands ........................................................................................................87

Trademarks .............................................................................................................................88

Risk & Safety ...........................................................................................................................90

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CF8.2 Extract 4 ed XML 032508 PGD UNP ed0423

BINAP/SEGPHOS® Ligands and Complexes

Since the development of BINAP by Noyori 20 years ago, extensiveresearch has been accomplished using this chiral ligand. BINAP proved tobe one of the most versatile ligands, catalyzing a wide range of reactions,from hydrogenations to Heck cyclizations.1

The research team at Takasago International Corporation developed aseries of ligands and complexes for a plethora of catalyzed asymmetricreactions. Based on a biphenyl architecture, several phosphine ligandshave been synthesized. Two large families of ligands can bedistinguished, BINAP and SEGPHOS (Figure 1). BINAP is based on abisnaphthalene backbone with different phosphine derivatives.SEGPHOS is based on a bis(1,3‑benzodioxole) backbone with differentphosphine substituents. BINAP and SEGPHOS are highly reactive andselective in a variety of asymmetric hydrogenations. In conjunction withruthenium, rhodium, palladium and copper complexes, these ligandsallow for enantioselectivities of up to >99%.

Rhodium-Catalyzed 1,4‑Additionof Arylboronic Acids to CoumarinsChen et al. presented the asymmetric synthesis of arylated coumarins.2

The importance of this transformation with coumarin precursors isillustrated with the synthesis of (R)-tolterodine, a urological drug that canbe readily obtained following the asymmetric arylation. Using SEGPHOSand Rh(acac)(C2H4)2, the researchers were able to obtain the desiredarylated coumarins with a yield of 88% and ee of 99.6% (Scheme 1).

Copper-Catalyzed Asymmetric Alkenylationand PhenylationTomita et al. developed a new catalytic enantioselective method for chiralalcohol and diarylmethanol synthesis.3 This new method is a greatalternative to the kinetic resolution using the Sharpless epoxidation orthe asymmetric addition of alkenylzinc reagents to carbonyl compounds,for the synthesis of chiral allylic alcohols. Furthermore, the transformationcan be achieved using air- and moisture-stable alkenylsilanes. UsingCuF2 ⋅ H2O with DTBM-SEGPHOS, the aryl aldehyde is reacted with avariety of trimethoxysilane derivatives (Scheme 2). Excellentenantioselectivities were obtained from a wide range of aldehydes.

Copper-Catalyzed Asymmetric HydrosilylationsLipshutz et al. developed a new method for asymmetric hydrosilylationsof various ketones using a preformed DTBM-SEGPHOS ⋅ CuH species inthe presence of excess polymethylhydrosiloxane.4 High yields and ee'swere reported for a variety of ketones (Scheme 3). These chiral buildingblocks are precursors for the synthesis of various drugs and naturallyoccurring molecules.

Ruthenium-Catalyzed Asymmetric Hydrogenationof Amino KetonesOhkuma et al. reported a practical asymmetric hydrogenation reactionusing mild hydrogen pressure with a wide scope.5 The access to chiralalcohols from amino ketones is important for the synthesis ofphysiologically active compounds. In this new process, a diphosphine/diamine Ru catalyst is utilized. This complex is based on DM-BINAP and1,1‑di-4‑anisyl-2‑isopropyl-1,2‑ethylenediamine (DAIPEN) and aruthenium complex. Using a loading as low as 0.01 mol% of catalyst, thehydrogenation of various amino ketones was conducted with up to99% yield and up to 99.8% ee (Scheme 4). To illustrate the relevance ofthis new catalyst, Okuma et al. synthesized a series of known moleculesused in drug synthesis.

Ruthenium-Catalyzed AsymmetricReductive AminationShimizu and coworkers reported a new protocol en route to chiral aminoacid derivatives via reductive amination.6 Using a Ru-DM-SEGPHOScomplex, a variety of amino esters were obtained in one step from thecorresponding ketoesters in highly enantioselective fashion (up to>99% ee) (Scheme 5).

References: (1) Noyori, R.; Ohkuma, T. Angew. Chem., Int. Ed. 2001, 40, 40. (2) Chen, G.et al. Org. Lett. 2005, 7, 2285. (3) Tomita, D. et al. J. Am. Chem. Soc. 2005, 127, 4138.(4) Lipshutz, B. H. et al. Org. Lett. 2006, 8, 2969. (5) Ohkuma, T. et al. J. Am. Chem. Soc.2000, 122, 6510. (6) Shimizu, H. et al. Acc. Chem. Res. 2007, 40, 1385.

PR2

PR2

O

O

O

O

PR2

PR2

R =

CH3

CH3

CH3

OCH3

C(CH3)3

C(CH3)3

BINAP

TolBINAP

XylBINAP

CH3

CH3

DM-SEGPHOS

SEGPHOS

DTBM-SEGPHOS

Figure 1

O

H3C

O O

H3C

O

Ph

H3C

OH

N

Ph

B(OH)2

+

Rh(acac)(C2H4)2

(R)-SEGPHOS®

dioxane/H2O88%, 99.6% ee (R)-Tolterodine

Scheme 1

R

O

HSi(OMe)3

R

OH

OH OH

Cl

OH

H3C

+

1. CuF2•2H2O

DTBM SEGPHOS®

2. TBAF

99%, 94% ee 99%, 97% ee 99%, 99 % ee

Scheme 2

OCH3

OH

O

Ar R

O

Ar R

OH(R)-DTBM-SEGPHOS®•CuH

PMHS

92%, 99.4% ee

N

OH

O

88%, 97.1% ee

F3C

CF3

OH

90%, 95% ee

Scheme 3

3Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich office, or visit safcglobal.com.

BIN

AP/SEGPHOS®Lig

ands

and

Complexes


O

O

N

COC6H5

OCH3

OCH3

O

OH

N

COC6H5

OCH3

OCH3H2

(S,S)-[Ru]

O

OHHN

OCH3

OCH3

HCl•

100%, 97% ee

F

O

N

N N

NF

F

OH

N

N N

NF

(S,S)-[Ru]

H2

97%, 99% ee

PR2

Ru

R2P

Cl

ClH2N

NH2

OCH3

H3CCH3

OCH3

R =

CH3

CH3

(S,S)-[Ru] =

Scheme 4

CO2MeNH2 AcOH

S*

CO2MeO

NH2 AcOHCO2Me

NH2 AcOHCO2Me

NH2 AcOHCO2Me

CO2MeNH2 AcOH

98% ee 99% ee 99% ee 96% ee

H2

AcONH4

Ru-(R)-DM-SEGPHOS

93% ee

Scheme 5

(R)-(+)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthalene, 97%

(R)-(+)-(1,1'-Binaphthalene-2,2'-diyl)bis(diphenylphos-phine); (R)-(+)-BINAP[76189‑55‑4]C44H32P2FW 622.67

P

P

295817-250MG 250 mg

295817-1G 1 g

295817-5G 5 g

(R)-BINAP 8

(R)-(+)-2,2′-Bis(diphenylphosphino)-1,1′-binaph-thalene; (R)-(+)-(1,1'-Binaphthalene-2,2'-diyl)bis(diphenylphosphine); (R)-(+)-BINAP[76189‑55‑4]C44H32P2FW 622.67

P

P

(R)-(+)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl693065-100MG 100 mg

693065-500MG 500 mg

(S)-(−)-2,2'-Bis(diphenylphosphino)-1,1'-binaphthalene, 97%

(S)-(−)-BINAP; (S)-(−)-(1,1'-Binaphthalene-2,2'-diyl)bis(diphenylphosphine)[76189‑56‑5]C44H32P2FW 622.67

P

P

295825-250MG 250 mg

295825-1G 1 g

295825-5G 5 g

(S)-BINAP 8

(S)-(−)-BINAP; (S)-(−)-2,2'-Bis(diphenylphosphino)-1,1'-binaphthalene; (S)-(−)-(1,1'-Binaphthalene-2,2'-diyl)bis(diphenylphosphine)[76189‑56‑5]C44H32P2FW 622.67

P

P

(S)-(−)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl693057-100MG 100 mg

693057-500MG 500 mg

(R)-H8-BINAP 8

(R)-(+)-2,2′-Bis(diphenylphospino)-5,5′,6,6′,7,7′,8,8′-octahydro-1,1′-binaphthyl; [(1R)-5,5′,6,6′,7,7′,8,8′-octahydro-[1,1′-binaphthalene]-2,2′-diyl]bis[diphenyl-phosphine][139139‑86‑9]C44H40P2FW 630.74

P

P

692387-50MG 50 mg

692387-100MG 100 mg

4 TO ORDER: Contact your local Sigma-Aldrich office (see back cover) or visit sigma-aldrich.com/chemicalsynthesis.sigma-aldrich.com

BIN

AP/SEGPHOS®Ligands

andComplexes

http://www.sigmaaldrich.com/catalog/search/ProductDetail/ALDRICH/295817













(S)-H8-BINAP 8

(S)-(−)-2,2′-Bis(diphenylphospino)-5,5′,6,6′,7,7′,8,8′-octahydro-1,1′-binaphthyl[139139‑93‑8]C44H40P2FW 630.74

P

P

693014-50MG 50 mg

693014-100MG 100 mg

(R)-(+)-2,2′-Bis(di-p-tolylphosphino)-1,1′-binaphthyl, 97%

(R)-Tol-BINAP[99646‑28‑3]C48H40P2FW 678.78

P

P

CH3

CH3

CH3

CH3

668966-250MG 250 mg

668966-1G 1 g

(R)-T-BINAP 8

(R)-(+)-2,2′-Bis(di-p-tolylphosphino)-1,1′-binaph-thyl; (R)-Tol-BINAP[99646‑28‑3]C48H40P2FW 678.78 P

P

CH3

CH3

CH3

CH3

693049-100MG 100 mg

693049-500MG 500 mg

(S)-(−)-2,2′-Bis(di-p-tolylphosphino)-1,1′-binaphthyl, 97%

(S)-Tol-BINAP[100165‑88‑6]C48H40P2FW 678.78

P

P

CH3

CH3

CH3

CH3

668974-250MG 250 mg

668974-1G 1 g

(S)-T-BINAP 8

(S)-(−)-2,2′-p-tolyl-phosphino)-1,1′-binaphthyl[100165‑88‑6]C48H40P2FW 678.78

P

P

CH3

CH3

CH3

CH3

693030-100MG 100 mg

693030-500MG 500 mg

(R)-DM-BINAP 8

(R)-(+)-2,2′-Bis[di(3,5-xylyl)phosphino]-1,1′-binaph-thyl; (R)-(+)-1,1′-Binaphthalene-2,2′-diyl)bis[bis(3,5-dimethyl-phenyl)phosphine][137219‑86‑4]C52H48P2FW 734.89

P

P

H3C CH3

CH3

CH3

CH3H3C

CH3CH3

692379-50MG 50 mg

692379-100MG 100 mg

(S)-DM-BINAP 8

(S)-(−)-2,2′-Bis[bis(3,5-dimethylphenyl)phosphino]-1,1′-binaphthyl; (S)-3,5-Xylyl-BINAP[135139‑00‑3]C52H48P2FW 734.89

P

P

H3C CH3

CH3

CH3

CH3H3C

CH3CH3

(S)-(-)-2,2′-Bis[di(3,5‑xylyl)phoshino]-1,1′-binaphthyl693022-50MG 50 mg

693022-100MG 100 mg

(R)-SEGPHOS® 8

(R)-(+)-5,5′-Bis(diphenylphosphino)-4,4′-bi-1,3-benzo-dioxole; [4(R)-(4,4′-bi-1,3-benzodioxole)-5,5′-diyl]bis[diphenylphosphine][244261‑66‑3]C38H28O4P2FW 610.57

P

P

O

O

O

O

692395-50MG 50 mg

692395-100MG 100 mg


BIN

AP/SEGPHOS®Lig

ands

and

Complexes


















(S)-SEGPHOS® 8

(S)-(−)-5,5′-Bis(diphenylphosphino)-4,4′-bi-1,3-benzo-dioxole[210169‑54‑3]C38H28O4P2FW 610.57

P

P

O

O

O

O

693006-50MG 50 mg

693006-100MG 100 mg

(R)-DM-SEGPHOS® 8

(R)-(+)-5,5′−Βis[di(3,5-xylyl)phosphino]-4,4′-bi-1,3-benzodioxole; [(4R)-(4,4′-bi-1,3-benzodioxole)-5,5′-diyl]bis[bis(3,5-dimethylphenyl)phosphine][850253‑53‑1]C46H44O4P2FW 722.79

P

P

H3C CH3

CH3

CH3

CH3H3C

CH3CH3

O

O

O

O

692476-50MG 50 mg

692476-100MG 100 mg

(S)-DM-SEGPHOS® 8

(S)-(−)-5,5′-Bis(diphenylphosphino)-4,4′-bi-1,3-benzodioxole[210169‑57‑6]C46H44O4P2FW 722.79

P

P

H3C CH3

CH3

CH3

CH3H3C

CH3CH3

O

O

O

O

692999-50MG 50 mg

692999-100MG 100 mg

(R)-DTBM-SEGPHOS® 8

(R)-(−)-5,5′-Bis[bis(3,5-di-tert-butyl-4-methoxy-phenyl)phosphino]-4,4′-bi-1,3-benzodioxole;[(4R)-(4,4′-bi-1,3-benzodioxole)-5,5′-diyl]bis[bis(3,5-di-tert-butyl-4-methoxyphenyl)phosphine][566940‑03‑2]C74H100O8P2FW 1179.53

P

P

t-Bu t-Bu

t-Bu

t-Bu

t-But-Bu

t-But-Bu

O

O

O

O

OCH3

OCH3

OCH3

OCH3

692484-50MG 50 mg

692484-100MG 100 mg

(S)-DTBM-SEGPHOS® 8

(S)-(+)-5,5′-Bis[di(3,5-di-tert-butyl-4-methoxy-phenyl)phosphino]-4,4′-bi-1,3-benzodioxole[210169‑40‑7]C74H100O8P2FW 1179.53 P

P

t-Bu t-Bu

t-Bu

t-Bu

t-But-Bu

t-But-Bu

O

O

O

O

OCH3

OCH3

OCH3

OCH3

692980-50MG 50 mg

692980-100MG 100 mg

[(R)-(+)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl]palladi-um(II) chloride, 97%

[115826‑95‑4]C44H32Cl2P2PdFW 800.00 P

P

Ph

Ph

Ph

Ph

PdCl

Cl

LR: 20/21/22-36/37/38 S: 26-37/39

342335-100MG 100 mg

(R)-[(RuCl(BINAP))2(μ-Cl)3[NH2Me2] 8

PRu

P

PRu

PPh

Ph

PhPh

PhPh

PhPh Cl

Cl

Cl H3C N CH3

H

HClCl

Dimethylammonium dichlorotri(μ-chloro)bis[(R)-(+)-2,2′-bis(diphenyl-phosphino)-1,1′-binaphthyl]diruthenate(II)[199684‑47‑4]C90H72Cl5NP4Ru2FW 1670.84

692433-100MG 100 mg

692433-500MG 500 mg

(S)-[(RuCl(BINAP))2(μ-Cl)3][NH2Me2] 8

PRu

P

PRu

PPh

Ph

PhPh

PhPh

PhPh Cl

Cl

Cl H3C N CH3

H

HClCl

Dimethylammonium dichlorotri(μ-chloro)bis[(S)-(−)-2,2′-bis(diphenyl-phosphino)-1,1′-binaphthyl]diruthenate(II)[199541‑17‑8]C90H72Cl5NP4Ru2FW 1670.84

JR: 11

693138-100MG 100 mg

693138-500MG 500 mg

(R)-[(RuCl(H8-BINAP))2(μ-Cl)3][NH2Me2] 8

P

PRu

ClCl

Cl

P

PRu

PhPh

PhPh

PhPh

PhPh

Cl Cl H3C N CH3

H

H

Dimethylammonium dichlorotri(μ-chloro)bis[(R)-(+)-2,2′-bis(diphenyl-phosphino)-5,5′,6,6′,7,7′,8,8′-octahydro-1,1′-binaphthyl]diruthenate(II)[204933‑84‑6]C90H88Cl5NP4Ru2FW 1686.97

692190-50MG 50 mg

692190-100MG 100 mg


BIN

AP/SEGPHOS®Ligands

andComplexes



















(S)-[(RuCl(H8-BINAP))2(μ-Cl)3][NH2Me2] 8

P

PRu

ClCl

Cl

P

PRu

PhPh

PhPh

PhPh

PhPh

Cl Cl H3C N CH3

H

H

Dimethylammonium dichlorotri(μ-chloro)bis[(S)-(−)-2,2′-bis(diphenyl-phosphino)-5,5′,6,6′,7,7′,8,8′-octahydro-1,1′-binaphthyl]diruthenate(II)C90H88Cl5NP4Ru2FW 1686.97

693324-50MG 50 mg

693324-100MG 100 mg

(R)-[(RuCl(T-BINAP))2(μ-Cl)3[NH2Me2] 8

P

P

P

PRu

ClCl

Cl

Ru

Cl

Cl

H3C N CH3

H

H

H3C CH3

CH3H3C H3C CH3

CH3H3C

Dimethylammonium dichlorotri(μ-chloro)bis[(R)-(+)-2,2′-bis(di-p-tolyl-phosphino)-1,1′-binaphthyl]diruthenate(II)[749935‑02‑2]C98H88Cl5NP4Ru2FW 1783.05

692441-100MG 100 mg

692441-500MG 500 mg

(S)-[(RuCl (T-BINAP))2(μ-Cl)3[NH2Me2] 8

P

P

P

PRu

ClCl

Cl

Ru

Cl

Cl

H3C N CH3

H

H

H3C CH3 H3C CH3

CH3H3CCH3H3C

Dimethylammonium dichlorotri(μ-chloro)bis[(S)-(−)-2,2′-bis(di-p-tolyl-phosphino)-1,1′-binaphthyl]diruthenate(II)[309735‑86‑2]C98H88Cl5NP4Ru2FW 1783.05

JR: 11

693146-100MG 100 mg

693146-500MG 500 mg

(R)-[(RuCl(DM-BINAP))2(μ-Cl)3][NH2Me2] 8

P

P

P

PRu

ClCl

Cl

Ru

Cl

Cl

H3C N CH3

H

H

H3C

CH3 CH3

H3CCH3

CH3CH3

CH3

CH3

CH3CH3

H3CCH3

CH3

H3C

CH3

Dimethylammonium dichlorotri(μ-chloro)bis[(R)-(+)-2,2′-bis[di(3,5‑xylyl)phosphino]-1,1′-binaphthyl]diruthenate(II)C106H104Cl5NP4Ru2FW 1895.27

JR: 11

692468-50MG 50 mg

692468-100MG 100 mg

(S)-[(RuCl(DM-BINAP))2(μ-Cl)3][NH2Me2] 8

P

P

P

PRu

ClCl

Cl

Ru

Cl

Cl

H3C N CH3

H

H

H3C

CH3 CH3

H3CCH3

CH3CH3

CH3

CH3

CH3CH3

H3CCH3

CH3

H3C

CH3

Dimethylammonium dichlorotri(μ-chloro)bis[(S)-(−)-2,2′-bis[di-(3,5‑xylyl)phosphino]-1,1′-binaphthyl]diruthenate(II)C106H104Cl5NP4Ru2FW 1895.27

LR: 36/37 S: 26-36

693154-50MG 50 mg

693154-100MG 100 mg

(R)-[(RuCl(SEGPHOS®))2(μ-Cl)3][NH2Me2] 8

P

PRu

ClCl

Cl

P

PRu

PhPh

PhPh

PhPh

PhPh

Cl Cl H3C N CH3

H

H

O

O

O

O

O

O

O

O

Dimethylammonium dichlorotri(μ-chloro)bis[(R)-(+)-5,5′-bis(diphenyl-phosphino)-4,4′-bi-1,3‑benzodioxole]diruthenate(II)[346457‑41‑8]C78H64Cl5NO8P4Ru2FW 1646.64

692204-50MG 50 mg

692204-100MG 100 mg


BIN

AP/SEGPHOS®Lig

ands

and

Complexes














(S)-[(RuCl(SEGPHOS®))2(μ-Cl)3][NH2Me2] 8

P

PRu

ClCl

Cl

P

PRu

PhPh

PhPh

PhPh

PhPh

Cl Cl H3C N CH3

H

H

O

O

O

O

O

O

O

O

Dimethylammonium dichlorotri(μ-chloro)bis[(S)-(−)-5,5′-bis(diphenyl-phosphino)-4,4′-bi-1,3‑benzodioxole]diruthenate(II)[488809‑34‑3]C78H64Cl5NO8P4Ru2FW 1646.64

693162-50MG 50 mg

693162-100MG 100 mg

(R)−[(RuCl(DM−SEGPHOS®)2(μ−Cl)3][NH2Me2] 8

P

P

P

PRu

ClCl

Cl

Ru

Cl

Cl

H3C N CH3

H

H

CH3

H3C

CH3

CH3

H3C

CH3CH3

CH3

CH3

CH3CH3

H3CCH3

CH3

H3C

CH3

O

O

O

O

O

O

O

O

Dimethylammonium dichlorotri(μ−chloro)bis[(R)−(+)−5,5′−bis[di(3,5−xylyl)phosphino]−4,4′−bi−1,3−benzodioxole]diruthenate(II)C94H96Cl5NO8P4Ru2FW 1871.07

692212-50MG 50 mg

692212-100MG 100 mg

(S)-[(RuCl(DM-SEGPHOS®))2(μ-Cl)3][NH2Me2] 8

P

P

P

PRu

ClCl

Cl

Ru

Cl

Cl

H3C N CH3

H

H

CH3

H3C

CH3

CH3

H3C

CH3CH3

CH3

CH3

CH3CH3

H3CCH3

CH3

H3C

CH3

O

O

O

O

O

O

O

O

Dimethylammonium dichlorotri(μ-chloro)bis[(S)-(−)-5,5′-bis[di(3,5‑xylyl)phosphino]-4,4′-bi-1,3‑benzodioxole]diruthenate(II)C94H96Cl5NO8P4Ru2FW 1871.07

JR: 11

693170-50MG 50 mg

693170-100MG 100 mg

(R)-RuCl[(p-cymene)(BINAP)]Cl 8

Chloro[(R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl](p-cymene)ruthenium(II)chloride[145926‑28‑9]C54H46Cl2P2RuFW 928.87

P

P

RuCl

Cl

CH3

H3CCH3

Ph Ph

Ph Ph

692492-100MG 100 mg

692492-500MG 500 mg

(S)-RuCl[(p-cymene(BINAP)Cl 8

Chloro[(S)-(−)-2,2′-bis(diphenylphosphino)-1,1′−binaphthyl](p-cymene)ruthenium(II)chloride[130004‑33‑0]C54H46Cl2P2RuFW 928.87

P

P

RuCl

Cl

CH3

H3CCH3

Ph Ph

Ph Ph

LR: 36/37/38 S: 26

692972-100MG 100 mg

692972-500MG 500 mg

(R)-RuCl[p-cymene)(H8-BINAP)]Cl 8

Chloro[(R)−(+)−2,2′−bis(diphenylphosphino)−5,5′,6,6′,7,7′,8,8′−octahydro−1,1′−binaphthyl](p-cymene)ruthenium(II) chlorideC54H54Cl2P2RuFW 936.93

P

PRu

PhPh

PhPh

Cl

CH3

Cl

CH3H3C

692514-50MG 50 mg

692514-100MG 100 mg

(S)-RuCl[(p-cymene)(H8-BINAP)]Cl 8

Chloro[(S)-(−)-2,2′−bis(diphenylphosphino)-5,5′,6,6′,7,7′,8,8′-octahydro-1,1′−binaphthyl](p-cymene)ruthenium(II) chlorideC54H54Cl2P2RuFW 936.93

P

P

RuCl

Cl

CH3

H3CCH3

Ph Ph

Ph Ph

693111-50MG 50 mg

693111-100MG 100 mg

(R)-RuCl[(p-cymene)(T-BINAP)]Cl 8

Chloro[(R)-(+)-2,2′-bis(di-p-tolylphosphino)-1,1′-binaphthyl](p-cymene)ruthenium(II)chloride[131614‑43‑2]C58H54Cl2P2RuFW 984.97

P

P

RuCl

Cl

CH3

H3CCH3

H3C CH3

CH3H3C

692506-100MG 100 mg

692506-500MG 500 mg


BIN

AP/SEGPHOS®Ligands

andComplexes


















(S)-RuCl[(p-cymene)(T-BINAP)]Cl 8

Chloro[(S)-(−)-2,2′-bis(di-p-tolylphosphino)-1,1′-binaphthyl](p-cymene)ruthenium(II)chloride[228120‑95‑4]C58H54Cl2P2RuFW 984.97

P

P

RuCl

Cl

CH3

H3CCH3

H3C CH3

CH3H3C

692964-100MG 100 mg

692964-500MG 500 mg

(R)−RuCl[(p−cymene)(DM−BINAP)]Cl 8

Chloro[(R)−(+)−2,2′−bis(di−(3,5−xylyl)phosphino)−1,1′−binaphthyl](p−cymene)ruthenium(II) chlorideC62H62Cl2P2RuFW 1041.08

P

P

RuCl

Cl

H3C

CH3CH3

CH3

H3C

CH3 CH3

CH3

CH3

H3CCH3

692409-50MG 50 mg

692409-100MG 100 mg

(S)-RuCl[(p-cymene)(DM-BINAP)]Cl 8

Chloro[(S)-(−)-2,2′-bis(di-(3,5-xylyl)phosphino)-1,1′-binaphthyl](p-cymene)ruthenium(II) chlorideC62H62Cl2P2RuFW 1041.08

P

P

RuCl

Cl

H3C

CH3CH3

CH3

H3C

CH3 CH3

CH3

CH3

H3CCH3

693103-50MG 50 mg

693103-100MG 100 mg

(R)−RuCl[(p−cymene)(SEGPHOS®)]Cl 8

Chloro[(R)-(+)-5,5′-bis(diphenylphosphino)-4,4′−bi−1,3−benzodioxole](p-cymene)ruthenium(II) chlorideC48H42Cl2O4P2RuFW 916.77

P

P

RuCl

Cl

CH3

H3CCH3

Ph Ph

Ph Ph

O

O

O

O

692522-50MG 50 mg

692522-100MG 100 mg

(S)-RuCl[(p-cymene)(SEGPHOS®)]Cl 8

Chloro[(S)-(−)-5,5′-bis(diphenylphosphino)-4,4′-bi-1,3-benzodioxole](p-cymene)ruthenium(II) chlorideC48H42Cl2O4P2RuFW 916.77

P

P

RuCl

Cl

CH3

H3CCH3

Ph Ph

Ph Ph

O

O

O

O

692956-50MG 50 mg

692956-100MG 100 mg

(R)-RuCl[(p-cymene)(DM-SEGPHOS®)]Cl 8

Chloro[(R)−(+)−5,5′−bis[di(3,5−xylyl)phosphino]−4,4′−bi−1,3−benzodioxole](p−cymene)ruthenium(II) chlorideC56H58Cl2O4P2RuFW 1028.98

P

P

RuCl

Cl

H3C

CH3CH3

CH3

H3C

CH3 CH3

CH3

CH3

H3CCH3

O

O

O

O

692417-50MG 50 mg

692417-100MG 100 mg

(S)-RuCl[(p-cymene)(DM-SEGPHOS®)]Cl 8

Chloro[(S)-(–)-5,5′-bis[di(3,5-xylyl)phosphino]-4,4′-bi-1,3-benzodioxole](p-cymene)ruthenium(II) chlorideC56H58Cl2O4P2RuFW 1028.98

P

P

RuCl

Cl

H3C

CH3CH3

CH3

H3C

CH3 CH3

CH3

CH3

H3CCH3

O

O

O

O

692948-50MG 50 mg

692948-100MG 100 mg

(R)-RuCl[(p-cymene)(DTBM-SEGPHOS®)]Cl 8

Chloro[(R)−(−)5,5′−bis[bis(3,5−di−tert−butyl−4−methoxyphenyl)phosphino]−4,4′−bi−1,3−benzodioxole](p−cymene)ruthenium(II)chlorideC84H114Cl2O8P2RuFW 1485.72

P

P

RuCl

CH3

H3CCH3

O

O

O

O

Cl

H3CO OCH3

OCH3H3COt-Bu

t-Bu

t-Bu

t-Bu

t-Bu

t-But-Bu

t-Bu

692425-50MG 50 mg

692425-100MG 100 mg


BIN

AP/SEGPHOS®Lig

ands

and

Complexes


















(S)-RuCl[(p-cymene)(DTBM-SEGPHOS®)]Cl 8

Chloro[(S)-(+)-5,5′-bis[di(3,5-di-tert-butyl-4-methoxyphenyl)phosphino]-4,4′-bi-1,3-benzo-dioxole](p-cymene)ruthenium(II) chlorideC84H114Cl2O8P2RuFW 1485.72

P

P

RuCl

CH3

H3CCH3

O

O

O

O

Cl

H3CO t-But-Bu OCH3

t-But-Bu

H3CO t-Bu

t-Bu

t-Bu OCH3

t-Bu

693073-50MG 50 mg

693073-100MG 100 mg

RuCl2[(R)−DM−BINAP][(R)−DAIPEN] 8

P

P

RuN

NCl

Cl

H

HH

CH3

H3C

CH3

CH3

H3C

CH3 CH3

CH3

CH3

CH3

H

OCH3

OCH3

Dichloro[(R)−2,2′−bis[di(3,5−xylyl)phosphino]−1,1′−binaphthyl][(2R)−1,1−bis(4−methoxyphenyl)−3−methyl−1,2−butanediamine]ruthenium(II)[220114‑32‑9]C71H74Cl2N2O2P2RuFW 1221.28

692255-50MG 50 mg

692255-100MG 100 mg

RuCl2[(S)-(DM-BINAP)][(S)-DAIPEN] 8

P

P

RuN

NCl

Cl

H

HH

CH3

H3C

CH3

CH3

H3C

CH3 CH3

CH3

CH3

CH3

H

OCH3

OCH3

Dichloro[(S)-(−)-2,2′-bis[di(3,5‑xylyl)phosphino]-1,1′-binaphthyl][(2S)-(+)-1,1‑bis(4‑methoxyphenyl)-3‑methyl-1,2‑butanediamine]ruthenium(II)[220114‑01‑2]C71H74Cl2N2O2P2RuFW 1221.28

693227-50MG 50 mg

693227-100MG 100 mg

RuCl2[(R)−DM−BINAP][(R,R)−DPEN] 8

Dichloro[(R)−2,2′−bis[di(3,5−xylyl)phosphino]−1,1′−binaphthyl][(1R,2R)−1,2−diphenyl-ethylenediamine]ruthenium(II)[220114‑38‑5]C66H64Cl2N2P2RuFW 1119.15

P

P

RuN

NCl

Cl

H

HH

CH3

H3C

H3C

CH3 CH3

CH3

CH3

CH3

H

692301-50MG 50 mg

692301-100MG 100 mg

RuCl2[(S)-(DM-BINAP)][(S,S)-DPEN] 8

Dichloro[(S)-(−)-2,2′-bis[di(3,5-xylyl)phosphino]-1,1′-binaphthyl][(1S,2S)-(−)-1,2-diphenylethylenediamine]ruthenium(II)[220114‑03‑4]C66H64Cl2N2P2RuFW 1119.15

P

P

RuN

NCl

Cl

H

HH

CH3

H3C

H3C

CH3 CH3

CH3

CH3

CH3

H

693251-50MG 50 mg

693251-100MG 100 mg

RuCl2[(R)-DM-SEGPHOS®][(R)-DAIPEN] 8

P

P

RuN

NCl

Cl

H

HH

CH3

H3C

CH3

CH3

H3C

CH3 CH3

CH3

CH3

CH3

HO

O

O

O

OCH3

OCH3

Dichloro[(R)-5,5′-bis[di(3,5‑xylyl)phosphino]-4,4′-bi-1,3‑benzodioxole][(2R)-1,1‑bis(4‑methoxyphenyl)-3‑methyl-1,2‑butanediamine]ruthenium(II)C65H70Cl2N2O2P2RuFW 1145.19

692328-50MG 50 mg

692328-100MG 100 mg


BIN

AP/SEGPHOS®Ligands

andComplexes














RuCl2[(S)-(DM-SEGPHOS®)][(S)-DAIPEN] 8

P

P

RuN

NCl

Cl

H

HH

CH3

H3C

CH3

CH3

H3C

CH3 CH3

CH3

CH3

CH3

HO

O

O

O

OCH3

OCH3

Dichloro[(S)-(−)-5,5′-bis[di(3,5‑xylyl)phosphino]-4.4′-bi-1,3‑benzodioxole][(2S)-(+)-1,1‑bis(4‑methoxyphenyl)-3‑methyl-1,2‑butanediamine]ruthenium(II)C65H70Cl2N2O6P2RuFW 1209.18

693219-50MG 50 mg

693219-100MG 100 mg

RuCl2[(R)−(DM−SEGPHOS®)][(R,(R))−(DPEN)] 8

Dichloro[(R)−5,5′−bis[di(3,5−xylyl)phosphino]−4,4′−bi−1,3−benzodioxole][(1R,2R)−1,2−diphenylethylenediamine]ruthenium(II)C60H60Cl2N2O2P2RuFW 1075.05 P

P

RuN

NCl

Cl

H

HH

CH3

H3C

H3C

CH3 CH3

CH3

CH3

CH3

HO

O

O

O

692336-50MG 50 mg

692336-100MG 100 mg

RuCl2[(S)-(DM-SEGPHOS®)][(S,S)-DPEN] 8

Dichloro[(S)-5,5′-bis[di(3,5-xylyl)phosphino]-4,4′-bi-1,3-benzodioxole][(1S,2S)-1,2-diphenylethylenediamine]ruthenium(II)C60H60Cl2N2O4P2RuFW 1107.05 P

P

RuN

NCl

Cl

H

HH

CH3

H3C

H3C

CH3 CH3

CH3

CH3

CH3

HO

O

O

O

693200-50MG 50 mg

693200-100MG 100 mg

(R)-Ru(OAc)2(BINAP) 8

Diacetato[(R)-(+)-2,2′-bis(diphenylphosphino)-1,1′−binaphthyl]ruthenium(II)[325146‑81‑4]C48H38O4P2RuFW 841.83

P

PRu

Ph Ph

Ph Ph

OO

CH3

O

OCH3

692220-100MG 100 mg

692220-500MG 500 mg

(S)-Ru(OAc)2(BINAP) 8

Diacetato[(S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl]ruthenium(II)[261948‑85‑0]C48H38O4P2RuFW 841.83

P

P

Ph Ph

Ru

OO

CH3

O

OCH3

Ph Ph

693189-100MG 100 mg

693189-500MG 500 mg

(R)-Ru(OAc)2(H8-BINAP) 8

Diacetato[(R)-2,2′-bis(diphenylphosphino)-5,5′,6,6′,7,7′,8,8′-octahydro-1,1′-binaphthyl]ruthenium(II)[374067‑51‑3]C48H46O4P2RuFW 849.89

P

P

Ph Ph

Ru

OO

CH3

O

OCH3

Ph Ph

692166-50MG 50 mg

692166-100MG 100 mg

(S)-Ru(OAc)2(H8-BINAP) 8

Diacetato[(S)-(−)-2,2′-bis(diphenylphosphino)-5,5′,6,6′,7,7′,8,8′-octahydro-1,1′-binaphthyl]ruthenium(II)[142962‑95‑6]C48H46O4P2RuFW 849.89

P

P

Ru

OO

CH3

O

OCH3

Ph Ph

PhPh

LR: 36/37 S: 26

693278-50MG 50 mg

693278-100MG 100 mg

(R)-Ru(OAc)2(T-BINAP) 8

Diacetato[(R)-2,2′-bis(di-p-tolylphosphino)-1,1′-bi-naphthyl]ruthenium(II)[116128‑29‑1]C52H46O4P2RuFW 897.94

P

P

H3C CH3

Ru

OO

CH3

O

OCH3

H3C CH3

692239-100MG 100 mg

692239-500MG 500 mg

(S)-Ru(OAc)2(T-BINAP) 8

Diacetato[(S)-(−)-2,2′-bis(di-p-tolylphosphino)-1,1′-binaphthyl]ruthenium(II)[106681‑15‑6]C52H46O4P2RuFW 897.94

P

P

Ru

OO

CH3

O

OCH3

H3C CH3

CH3H3C

LR: 36/37 S: 26-36

693197-100MG 100 mg

693197-500MG 500 mg


BIN

AP/SEGPHOS®Lig

ands

and

Complexes




















(R)-Ru(OAc)2(DM-BINAP) 8

Diacetato[(R)-2,2′-bis[di(3,5-xylyl)phosphino]-1,1′-binaphtyl]ruthenium(II)[374067‑50‑2]C56H54O4P2RuFW 954.04

P

P

Ru

OO

CH3

O

OCH3

H3C

CH3 CH3

CH3

CH3

CH3CH3

H3C

692158-50MG 50 mg

692158-100MG 100 mg

(S)-Ru(OAc)2(DM-BINAP) 8

Diacetato[(S)-(−)-2,2′-bis[di(3,5-xylyl)phosphino]-1,1′−binaphthyl]ruthenium(II)[374067‑49‑9]C56H54O4P2RuFW 954.04

P

P

Ru

OO

CH3

O

OCH3

H3C

CH3 CH3

CH3

CH3

CH3CH3

H3C

693286-50MG 50 mg

693286-100MG 100 mg

(R)-Ru(OAc)2(SEGPHOS®) 8

Diacetato[(R)-5,5′-bis(diphenylphosphino)-4,4′-bi-1,3-benzodioxole]ruthenium(II)C42H34O8P2RuFW 829.73 P

PRu

Ph Ph

Ph Ph

O

O

O

O

OO

CH3

O

OCH3

692174-50MG 50 mg

692174-100MG 100 mg

(S)-Ru(OAc)2(SEGPHOS®) 8

Diacetato[(S)-(−)-5,5′-bis(diphenylphosphino)-4,4′-bi-1,3-benzodioxole]ruthenium(II)[373650‑12‑5]C42H34O8P2RuFW 829.73

P

PRu

Ph Ph

Ph Ph

O

O

O

O

OO

CH3

O

OCH3

693243-50MG 50 mg

693243-100MG 100 mg

(R)-Ru(OAc)2(DM-SEGPHOS®) 8

Diacetato[(R)-5,5′-bis[di(3,5-xylyl)phosphino]-4,4′-bi-1,3-benzodioxole]ruthenium(II)C50H50O8P2RuFW 941.94

P

P

Ru

OO

CH3

O

OCH3

H3C

CH3 CH3

CH3

CH3

CH3CH3

H3C

O

O

O

O

692182-50MG 50 mg

692182-100MG 100 mg

(S)-Ru(OAc)2(DM-SEGPHOS®) 8

Diacetato[(S)-(−)-5,5′-bis[di(3,5-xylyl)phosphino]-4,4′-bi-1,3-benzodioxole]ruthenium(II)C50H50O8P2RuFW 941.94

P

P

Ru

OO

CH3

O

OCH3

H3C

CH3 CH3

CH3

CH3

CH3CH3

H3C

O

O

O

O

693235-50MG 50 mg

693235-100MG 100 mg

Takasago (R)-SEGPHOS®/BINAP Ligands kit

Components(R)-DM-BINAP (Aldrich 692379) 50mg(R)-H8-BINAP (Aldrich 692387) 50mg(R)-SEGPHOS® (Aldrich 692395) 50mg(R)-DM-SEGPHOS® (Aldrich 692476) 50mg(R)-DTBM-SEGPHOS® (Aldrich 692484) 50mg(R)-T-BINAP (Aldrich 693049) 100mg(R)-BINAP (Aldrich 693065) 100mg

695270-1KT 1 kit

Takasago (R)-Ru Acetate Kit I

Components(R)-Ru(OAc)2(DM-BINAP) (Aldrich 692158) 50mg(R)-Ru(OAc)2(H8-BINAP) (Aldrich 692166) 50mg(R)-Ru(OAc)2(SEGPHOS

®) (Aldrich 692174) 50mg(R)-Ru(OAc)2(DM-SEGPHOS®) (Aldrich 692182) 50mg(R)-Ru(OAc)2(BINAP) (Aldrich 692220) 100mg(R)-Ru(OAc)2(T-BINAP) (Aldrich 692239) 100mg

695300-1KT 1 kit

Takasago (R)-Ru dimethylamine Kit I

Components(R)-[(RuCl(H8-BINAP))2(μ-Cl)3][NH2Me2] (Aldrich 692190) 50mg(R)-[(RuCl(SEGPHOS®))2(μ-Cl)3][NH2Me2] (Aldrich 692204) 50mg(R)−[(RuCl(DM−SEGPHOS®)2(μ−Cl)3][NH2Me2] (Aldrich 692212) 50mg(R)-[(RuCl(BINAP))2(μ-Cl)3[NH2Me2] (Aldrich 692433) 100mg(R)-[(RuCl(T-BINAP))2(μ-Cl)3[NH2Me2] (Aldrich 692441) 100mg(R)-[(RuCl(DM-BINAP))2(μ-Cl)3][NH2Me2] (Aldrich 692468) 50mg

695297-1KT 1 kit

Takasago (R,R)-Ru diamine Kit I

ComponentsRuCl2[(R)−DM−BINAP][(R)−DAIPEN] (Aldrich 692255) 50mgRuCl2[(R)−DM−BINAP][(R,R)−DPEN] (Aldrich 692301) 50mgRuCl2[(R)-DM-SEGPHOS®][(R)-DAIPEN] (Aldrich 692328) 50mgRuCl2[(R)−(DM−SEGPHOS®)][(R,(R))−(DPEN)] (Aldrich 692336) 50mg

695319-1KT 1 kit

Takasago (R)-Ru Cymene Kit I

Components(R)−RuCl[(p−cymene)(DM−BINAP)]Cl (Aldrich 692409) 50mg(R)-RuCl[(p-cymene)(DM-SEGPHOS®)]Cl (Aldrich 692417) 50mg(R)-RuCl[(p-cymene)(DTBM-SEGPHOS®)]Cl (Aldrich 692425) 50mg(R)-RuCl[(p-cymene)(BINAP)]Cl (Aldrich 692492) 100mg(R)-RuCl[(p-cymene)(T-BINAP)]Cl (Aldrich 692506) 100mg(R)-RuCl[p-cymene)(H8-BINAP)]Cl (Aldrich 692514) 50mg(R)−RuCl[(p−cymene)(SEGPHOS®)]Cl (Aldrich 692522) 50mg

695289-1KT 1 kit


BIN

AP/SEGPHOS®Ligands

andComplexes


















Chiral Chromatography Products

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CHIROBIOTIC

CYCLOBOND

CHIRALDEX

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Ad_ChemF-5-08_ed.indd 1Ad_ChemF-5-08_ed.indd 1 5/6/2008 4:38:18 PM5/6/2008 4:38:18 PM

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Solvias® Ligand Portfolio for Enantioselective HydrogenationHans-Ulrich Blaser, Garrett Hoge, Matthias Lotz, Benoît Pugin,Anita Schnyder and Felix SpindlerSolvias AG, P.O. Box, CH-4002 Basel, SwitzerlandContact: Dr. Garrett Hoge, Product Manager Catalysis,[email protected]

Today's Solvias Ligand Portfolio has its roots in the development of theJosiphos ligands and the successful implementation in the(S)-metolachlor process—the largest industrial enantioselectivemanufacturing process—in the former Ciba-Geigy. Over the last decade,several additional ligand families have been added, either via Solvias'own research or via licensing from other companies.1 The centralconcept for all Solvias ligands is their modularity, usually via theintroduction of different phosphino moieties in the very last stages oftheir synthesis. This allows the easy tuning of the steric and electronicproperties and, thereby, the adaptation to the needs of a specificreaction. All ligands in the Solvias portfolio are available on a researchscale with very short lead times; several ligands are being producedregularly in multikilogram quantities. The number of ligands within thedifferent families varies between 10 to >100; therefore, it is not practicalto have all of them available in a catalog. For this reason the membersoffered via Sigma-Aldrich® are a selection representing different stericand electronic properties. Further derivatives for optimization or finetuning are usually available on request from Solvias.

MeOBIPHEPIn many respects, the catalytic profile of the MeOBIPHEP ligands is rathersimilar to that of other atropisomeric diphosphines such as BINAP and itsmany analogs.1–3 The nature of the PR2 group strongly influences thecatalytic performance of the metal complexes, and the ligands availablehave different steric bulk.1 MeOBIPHEP complexes are highly effective forthe hydrogenation of α- and β-functionalized ketones (Figure 1), thehydrogenation of allylic alcohols and α,β-unsaturated esters (Figure 2),the hydrogenation of heteroarenes (Figure 3) and a variety of syntheti-cally useful C–C coupling reactions (Figure 4).

References: (1)(a) Blaser, H.U. et al. Chimica Oggi 2007, 25(2), Supplement CatalyticApplications, p 8. (b) Blaser, H.U. et al. Acc. Chem. Res. 2007, 40, 1240. (2) Tang, W.;Zhang, X. Chem. Rev. 2003, 103, 3029. (3) Schmid, R. et al. Pure Appl. Chem. 1996, 68,131. (4) Ratovelomanana-Vidal, V. et al. Adv. Synth. Catal. 2003, 345, 261. (5) Blanc, D. etal. J. Organomet. Chem. 2000, 603, 128. (6) Bertus, P. et al. Tetrahedron: Asymmetry 1999,10, 1369. (7) Cederbaum, F. et al. Adv. Synth. Catal. 2004, 346, 842. (8) Mordant, C. et al.Synthesis 2003, 2405. (9) Makino, K. et al. Org. Lett. 2006, 8, 4573. (10) Schmid, R.;Scalone M. in Comprehensive Asymmetric Catalysis; Jacobsen, E. N.; Yamamoto, H.; Pfaltz,A., Eds., Springer : Berlin, 1999; p 1439. (11) Crameri, Y. et al. Chimia 1997, 51, 303.(12) Netscher, T. et al. in Large Scale Asymmetric Catalysis; Blaser, H.-U.; Schmidt, E., Eds.,Wiley-VCH: Weinheim, 2003; p 71. (13) Bulliard, M. et al. Org. Process Res. Devel. 2001, 5,438. (14) Wang, W-B. et al. J. Am. Chem. Soc. 2003, 125, 10536. (14) Kong, J. R.; Krische,M. J. J. Am. Chem. Soc. 2006, 128, 16040. (15) Han, X.; Widenhoefer, R. A. P. M. Org. Lett.2006, 8, 3801. (16) Koh, J. H. et al. Org. Lett. 2001, 3, 1233. (17) Tschoerner, M. et al.Organometallics 1999, 18, 670.

A101-129510

PH3COH3CO

P

A101-229511

PH3COH3CO

P

A109-129512

PH3COH3CO

P

t-Bu t-But-Bu

t-Bu

OCH3

OCH3

t-Bu

OCH3

t-But-Bu

OCH3

t-Bu

A109-229513

PH3COH3CO

P

t-Bu t-But-Bu

t-Bu

OCH3

OCH3

t-Bu

OCH3

t-But-Bu

OCH3

t-Bu

R

OX

R

OHX

O

ClO

HN

R

OH

ClO

HN

R

O

Cl

COOMe

MeO

OH

Cl

COOMe

MeO

Ar

O

NH2.HCl

COOMe Ar

OH

NHBz

COOMe

Ru / A101

88-97% eeR = alkyl, (subst) Ph, NpX = COOR', SO2Ph

1-10 bar, 40-80 °C

90 - 93% eeMeOH, 1 N HCl80 bar, 60°C

[Ru(p-cymene)I2]2 / A101-1s/c 4000, 20 h

bench scale, Solvias

95% ee, 92% de

1) Ir / A101AcOH / NaOAc

92% ee, dr >992) Bz2O, TEA, THF

[4-6]

[7]

[8]

[9]

Ru / A101

CH2Cl2

Figure 1

OH OH

NN

O

OCOOHxNEt3

F

COOH

Ru / A10120 °C, 60 baree 99%; TON 30,000; TOF 1500 h-1pilot scale, Roche [10, 12]

Ru / p-Tol-MeOBIPHEP20 °C, 60 barde 99%; TON 150,000; TOF 13,000 h-1pilot process, Roche [10, 12]

Ru / p-Tol-MeOBIPHEP60 °C, 70 baree >99%; TON 20,000; TOF 830 h-1pilot scale, Roche [10]

Ru / A10130 °C, 270 bar (continuous)ee 94%;TON 1000;TOF ~400 h-1pilot process, Roche [10, 11]

Figure 2

N R

R'

NH

R

R'[Ir(cod)2Cl]2 / A101

toluene, I2

50 bar, 25°C

s/c 100, 18 h

80-99%, 86-96% eeR = (subst) alkylR' = H, F, Me, MeO

[14]

Figure 3

R R'

O

R

OH

R'

RN

"RR'

R'

RN

R"R'

R'

H

O

COOEt

OH

COOEt

ORAr

OR

2 +

80%, 89% ee

Rh / A101

DCE, Ph3CCOH, Na2SO4

1 bar, 25 °C

56-96%, up to 90% ee

Pt(A109)Cl2AgOTf

MeOH, 25°C

up to 85% ee

+Pt / (4-tBu-Ph-MeOBIPHEP)

CH2Cl2, -50 °Cprotic additives

[15]

[16]

[17]

+ArOTf

Pd / A101

acetone, 40 °CNEt(i-Pr)2R = H, Me

+ isomer

>98% ee

[18]

Figure 4


Solvias®

LigandPortfo

lio


(R)-(+)-(6,6′-Dimethoxybiphenyl-2,2′-diyl)bis(diphenylphos-phine), ≥97.0% (CHN)

(R)-(+)-MeO-BIPHEP; (R)-(+)-2,2′-Bis(diphenylphos-phino)-6,6′-dimethoxy-1,1′-biphenyl; SL-A101-1[133545‑16‑1]C38H32O2P2FW 582.61

PH3COH3CO

P

29510-100MG 100 mg

29510-500MG 500 mg

29510-1G 1 g

29510-5G 5 g

(S)-(-)-(6,6′-Dimethoxybiphenyl-2,2′-diyl)bis(diphenylphos-phine), ≥97.0%

(S)-(−)-2,2′-Bis(diphenylphosphino)-6,6′-dimethoxy-1,1′-biphenyl; (S)-(−)-MeO-BIPHEP; SL-A101-2[133545‑17‑2]C38H32O2P2FW 582.61

PH3COH3CO

P

29511-100MG 100 mg

29511-500MG 500 mg

29511-1G 1 g

29511-5G 5 g

(R)-(6,6′-Dimethoxybiphenyl-2,2′-diyl)bis[bis(3,5‑di-tert-bu-tyl-4‑methoxyphenyl)phosphine], ≥97.0% (CHN)

(R)-3,5-t-Bu-4-MeO-MeOBIPHEP; SL-A109-1;(R)-[6,6′-Dimethoxy(1,1′-biphenyl)-2,2′-diyl]bis{bis[3,5-bis(1,1-dimethylethyl)-4-methoxy-phenyl]phosphine}[352655‑61‑9]C74H104O6P2FW 1151.56

PH3COH3CO

P

t-Bu t-But-Bu

t-Bu

OCH3

OCH3

t-Bu

OCH3

t-But-Bu

OCH3

t-Bu

29512-100MG 100 mg

29512-500MG 500 mg

29512-1G 1 g

29512-5G 5 g

(S)-(6,6′-Dimethoxybiphenyl-2,2′-diyl)bis[bis(3,5‑di-tert-bu-tyl-4‑methoxyphenyl)phosphine], ≥97.0% (CHN)

SL-A109-2; (S)-3,5-t-Bu-4-MeO-MeOBIPHEP;(S)-[6,6′-Dimethoxy(1,1′-biphenyl)-2,2′-diyl]bis{bis[3,5-bis(1,1-dimethylethyl)-4-methoxy-phenyl]phosphine}C74H104O6P2FW 1151.56

PH3COH3CO

P

t-Bu t-But-Bu

t-Bu

OCH3

OCH3

t-Bu

OCH3

t-But-Bu

OCH3

t-Bu

29513-100MG 100 mg

29513-500MG 500 mg

29513-1G 1 g

29513-5G 5 g

(R)-(6,6′-Dimethoxybiphenyl-2,2′-diyl)bis(di-2-furyl-phosphine), ≥97.0% (CHN)

8

SL-A108-1; (R)-2-Furyl-MeOBIPHEP; (R)-(+)-2,2′-Bis(di-2-furylphosphino)-6,6′-dimethoxy-1,1′-biphenyl[145214‑57‑9]C30H24O6P2FW 542.46

P

PH3CO

H3CO O

O

O

O

29514-100MG 100 mg

29514-500MG 500 mg

29514-1G 1 g

29514-5G 5 g

(S)-(6,6′-Dimethoxybiphenyl-2,2′-diyl)bis(di-2-furyl-phosphine), ≥97.0% (CHN)

8

(S)-(−)-2,2′-Bis(di-2-furylphosphino)-6,6′-dimethoxy-1,1′-biphenyl; SL-A108-2; (S)-2-Furyl-MeOBIPHEP[145214‑59‑1]C30H24O6P2FW 542.46

P

PH3CO

H3CO O

O

O

O

29515-100MG 100 mg

29515-500MG 500 mg

29515-1G 1 g

29515-5G 5 g

(R)-(6,6′-Dimethoxybiphenyl-2,2′-diyl)bis[bis(3,5-dimethylphenyl)phosphine], ≥97.0% (CHN)

8

SL-A120-1; (R)-3,5-Xyl-MeOBIPHEP; (R)-2,2′-Bis[bis(3,5-dimethyl)phosphino]-6,6′-dimethoxy-1,1′-biphenyl[394248‑45‑4]C46H48O2P2FW 694.82

P

P

CH3H3C

CH3

CH3CH3

CH3H3C

CH3

H3CO

H3CO

29516-100MG 100 mg

29516-500MG 500 mg

29516-1G 1 g

29516-5G 5 g

(S)-(6,6′-Dimethoxybiphenyl-2,2′-diyl)bis[bis(3,5-dimethylphenyl)phosphine], ≥97.0% (CHN)

8

(S)-3,5-Xyl-MeOBIPHEP; SL-A120-2; (S)-2,2′-Bis[bis(3,5-dimethyl)phosphino]-6,6′-dimethoxy-1,1′-biphenyl[362634‑22‑8]C46H48O2P2FW 694.82

P

P

CH3H3C

CH3

CH3CH3

CH3H3C

CH3

H3CO

H3CO

29517-100MG 100 mg

29517-500MG 500 mg

29517-1G 1 g

29517-5G 5 g


Solvias®Lig

andPortfo

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(R)-(6,6′-Dimethoxybiphenyl-2,2′-diyl)bis(diisopropyl-phosphine), ≥97.0% (CHN)

8

SL-A116-1; (R)-iPr-MeOBIPHEP; (R)-2,2′-Bis(diisopro-pylphosphino)-6,6′-dimethoxy-1,1′-biphenyl[150971‑45‑2]C26H40O2P2FW 446.54

PH3CO

H3COP

CH3H3C

H3C CH3

CH3

CH3

CH3

CH3

29518-100MG 100 mg

29518-500MG 500 mg

29518-1G 1 g

29518-5G 5 g

(S)-(6,6′-Dimethoxybiphenyl-2,2′-diyl)bis(diisopropyl-phosphine), ≥97.0% (CHN)

8

SL-A116-2; (S)-iPr-MeOBIPHEP; (S)-2,2′-Bis(diisopro-pylphosphino)-6,6′-dimethoxy-1,1′-biphenyl[150971‑43‑0]C26H40O2P2FW 446.54

PH3CO

H3COP

CH3H3C

H3C CH3

CH3

CH3

CH3

CH3

29519-100MG 100 mg

29519-500MG 500 mg

29519-1G 1 g

29519-5G 5 g

(R)-(6,6′-Dimethoxybiphenyl-2,2′-diyl)bis[bis(4-methylphenyl)phosphine], ≥97.0% (CHN)

8

(R)-p-Tol-MeOBIPHEP; SL-A102-1; (R)-2,2′-Bis(di-p-tolylphosphino)-6,6′-dimethoxy-1,1′-biphenyl[133545‑24‑1]C42H40O2P2FW 638.71 P

PH3CO

H3CO

CH3

CH3

CH3

CH3

29520-100MG 100 mg

29520-500MG 500 mg

29520-1G 1 g

29520-5G 5 g

(S)-(6,6′-Dimethoxybiphenyl-2,2′-diyl)bis[bis(4-methyl-phenyl)phosphine], ≥97.0% (CHN)

8

SL-A102-2; (S)-p-Tol-MeOBIPHEP; (S)-2,2′-Bis(di-p-tolylphosphino)-6,6′-dimethoxy-1,1′-biphenyl[133545‑25‑2]C42H40O2P2FW 638.71 P

PH3CO

H3CO

CH3

CH3

CH3

CH3

29521-100MG 100 mg

29521-500MG 500 mg

29521-1G 1 g

29521-5G 5 g

(R)-(6,6′-Dimethoxybiphenyl-2,2′-diyl)bis[bis(3,5-di-tert-butylphenyl)phosphine], ≥97.0% (CHN)

8

SL-A121-1; (R)-3,5-t-Bu-MeOBIPHEP; (R)-2,2′-Bis[bis(3,5-di-tert-butyl)phosphino]-6,6′-dimethoxy-1,1′-biphenyl[192138‑05‑9]C70H96O2P2FW 1031.46

H3CO

H3CO

P

P

t-Bu t-Bu

t-Bu

t-Bu

t-Bu

t-Bu

t-But-Bu

29524-100MG 100 mg

29524-500MG 500 mg

29524-1G 1 g

29524-5G 5 g

(S)-(6,6′-Dimethoxybiphenyl-2,2′-diyl)bis[bis(3,5-di-tert-butylphenyl)phosphine], ≥97.0% (CHN)

8

SL-A121-2; (S)-3,5-t-Bu-MeOBIPHEP; (S)-2,2′-Bis[bis(3,5-di-tert-butyl)phosphino]-6,6′-dimethoxy-1,1'-biphenyl[167709‑31‑1]C70H96O2P2FW 1031.46

P

P

t-But-Bu

t-Bu

t-But-Bu

t-But-Bu

t-Bu

H3CO

H3CO

29525-100MG 100 mg

29525-500MG 500 mg

29525-1G 1 g

29525-5G 5 g

(R)-(6,6′-Dimethoxybiphenyl-2,2′-diyl)bis[bis(3,4,5-tri-methoxyphenyl)phosphine], ≥97.0% (CHN)

8

(R)-3,4,5-MeO-MeOBIPHEP; SL-A104-1; (R)-2,2′-Bis[bis(3,4,5-trimethoxyphenyl)phosphino]-6,6′-dimethoxy-1,1′-biphenyl[256390‑47‑3]C50H56O14P2FW 942.92

P

P

OCH3H3CO

OCH3

OCH3OCH3

OCH3H3CO

OCH3

H3CO

H3CO

OCH3

OCH3

OCH3

OCH3

29526-100MG 100 mg

29526-500MG 500 mg

29526-1G 1 g

29526-5G 5 g


Solvias®

LigandPortfo

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(S)-(6,6′-Dimethoxybiphenyl-2,2′-diyl)bis[bis(3,4,5-tri-methoxyphenyl)phosphine], ≥97.0% (CHN)

8

SL-A104-2; (S)-2,2′-Bis[bis(3,4,5-trimethoxy-phenyl)phosphino]-6,6′-dimethoxy-1,1′-biphenyl; (S)-3,4,5-MeO-MeOBIPHEP[927396‑01‑8]C50H56O14P2FW 942.92

P

P

OCH3H3CO

OCH3

OCH3OCH3

OCH3H3CO

OCH3

H3CO

H3CO

OCH3

OCH3

OCH3

OCH3

29527-100MG 100 mg

29527-500MG 500 mg

29527-1G 1 g

29527-5G 5 g

(R)-(6,6′-Dimethoxybiphenyl-2,2′-diyl)bis{bis[3,5-diiso-propyl-4-(dimethylamino)phenyl]phosphine}, ≥97.0%(CHN)

8

(R)-2,2′-Bis[bis(3,5-diisopropyl-4-dimethyl-aminophenyl)phosphino]-6,6′-dimethoxy-1,1′-biphenyl; (R)-3,5-iPr-4-NMe2-MeOBIPHEP; SL-A107-1[352655‑40‑4]C70H100N4O2P2FW 1091.52

H3CO

H3CO

P

P

i-Pr i-Pr

i-Pr

i-Pr

i-Pr

i-Pr

i-Pri-Pr

NCH3

CH3

NH3C CH3

NH3C CH3

29528-100MG 100 mg

29528-500MG 500 mg

29528-1G 1 g

29528-5G 5 g

(S)-(6,6′-Dimethoxybiphenyl-2,2′-diyl)bis{bis[3,5-diiso-propyl-4-(dimethylamino)phenyl]phosphine}, ≥97.0%(CHN)

8

SL-A107-2; (S)-3,5-iPr-4-NMe2-MeOBIPHEP;(S)-2,2′-Bis[bis(3,5-diisopropyl-4-dimethyl-aminophenyl)phosphino]-6,6′-dimethoxy-1,1′-biphenyl[352655‑40‑4]C70H100N4O2P2FW 1091.52

H3CO

H3CO

P

P

i-Pr i-Pr

i-Pr

i-Pr

i-Pr

i-Pr

i-Pri-Pr

NCH3

CH3

NH3C CH3

NH3C CH3

29529-100MG 100 mg

29529-500MG 500 mg

29529-1G 1 g

29529-5G 5 g

JosiphosThe Josiphos ligands arguably constitute one of the most versatile andsuccessful ligand families, second probably only to the BINAP ligands.Since the two phosphine groups are introduced in consecutive steps withvery high yields,1,2 a variety of ligands are readily available with widelydiffering steric and electronic properties. Up to now, only the(R,SFc)-family (and its enantiomers) but not the (R,RFc) diastereomers haveled to high enantioselectivities. At present, about 150 different Josiphosligands have been prepared and 40 derivatives are available in a ligandkit (12000) for screening and on a multikilogram scale for production.3

Catalytic applications of the Josiphos ligand family were reviewed up to2002.3 Until now, Josiphos ligands have been applied in 4 productionprocesses and about 5 or 6 pilot and bench scale processes involving Rh,Ir, and Ru catalyzed hydrogenation reactions of C=C and C=N bonds.4

Selected applications are summarized in Figure 1. The most importantapplication is undoubtedly the Ir/J005‑1 catalyzed hydrogenation of ahindered N-aryl imine of methoxyacetone, the largest knownenantioselective process operated for the enantioselective production ofthe herbicide (S)-metolachlor.2,5 The hydrogenation of tetrasubstitutedolefins was the key step for two production processes developed for thesynthesis of biotin by Lonza and of methyl dihydrojasmonate byFirmenich.6 Pilot processes were developed by Lonza for a building blockof crixivan and for dextromethorphane.6 Recently, Merck chemistsreported the unprecedented hydrogenation of unprotected dehydroβ-amino acid derivatives catalyzed by Rh-Josiphos with ee's up to 97%. Itwas shown that not only simple derivatives but also the complexintermediate for MK-0431 depicted in Figure 1 can be hydrogenatedsuccessfully. Regular production on a multiton/year scale with ee's up to98% has been started in 2006.7

Rh and Ir complexes with chiral Josiphos ligands are highly selective,active, and productive catalysts for various enantioselective reductions.Very high enantioselectivities were described for the enantioselectivehydrogenation of enamides, itaconic acid derivatives, acetoacetates aswell as N-aryl imines (in presence of acid and iodide) andphosphinylimines.3 Josiphos J001 is the ligand of choice for theCu catalyzed reduction of activated C=C bonds withpolymethylhydrosiloxane (PMHS) (Figure 2) with very highenantioselectivities for nitro alkenes,8 α,β-unsaturated ketones,9a

esters,9b,c and nitriles.10 Very recently, it was disclosed that Ru-Josiphos-pyridinyl-alkylamines complexes (best ligands J001 and J007) areextraordinarily effective for the enantioselective transfer hydrogenationof aryl ketones with turnover frequencies for full conversion exceeding20,000 h-1 (Figure 3).11

Josiphos complexes have been successfully applied to various asymmetriccatalytic coupling reactions such as allylic alkylation orhydroformylation.3 Selected recent examples are depicted in Figure 4.Feringa's group reported high ee's for the Cu catalyzed Michael additionof Grignard reagents to α,β-unsaturated esters,12a thioesters,12b,c andfor selected cyclic enones.12d The preferred ligands were J001 and J004.The Rh/J001 was very effective for the nucleophilic ring opening ofvarious oxabicyclic substrates leading to interesting new tetrahydro-naphthalene and cyclohexene derivatives.13a,b This reaction was scaledup to the kilogram scale.13c The Pd catalyzed opening of various cyclicanhydrides with Ph2Zn was described by Bercot and Rovis to occur withvery high ee's in presence of J001.14 Lorman et al.15 reported up to 95%ee for an intermolecular Heck reaction using a Pd/J001 catalyst.

Josiphos ligands were not only applied to enantioselective reactions butalso were shown to be useful for Pd catalyzed coupling reactions withvery high activities. Hartwig's group reported that Pd/J009 (88733 and88734) complexes were effective catalysts for the amination of arylhalides or sulfonates with ammonia,16a coupling of aryl halides orsulfonates with thiols,16b and Kumada coupling of aryl or vinyl tosylateswith Grignard reagents.16c

References: (1) Togni, A. et al. J. Am. Chem. Soc. 1994, 116, 4062. (2) For a scalablesynthesis of Ugi amine see Blaser, H. U. et al. Chimia 1999, 53, 275. (3) Blaser, H. U. et al.Topics in Catalysis 2002, 19, 3. (4) Blaser, H. U. et al. in Handbook of HomogeneousHydrogenation; de Vries, J. G.; Elsevier, C.J., eds., Wiley-VCH, 2007; p 1279. (5) Blaser, H.U. Adv. Synth. Catal. 2002, 344, 17. (6) For details see ref. 3. (7)(a) Rouhi, M. C&EN, 2004,82(37), 28. (b) Hsiao, Y. et al. J. Am. Chem. Soc. 2004, 126, 9918; (c) Kubryk, M.; Hansen,K. B. Tetrahedron: Asymmetry 2006, 17, 205; (d) Clausen, A. M. et al. Org. Process Res.Devel. 2006, 10, 723. (8)(a) Czekelius, C.; Carreira, E. M. Angew. Chem., Int. Ed. 2003, 42,4793. (b) Czekelius, C.; Carreira, E. M. Org. Lett. 2004, 6, 4575. (9)(a) Lipshutz, B. H.Servesko, J. M. Angew. Chem., Int. Ed. 2003, 42, 4789. (b) Lipshutz, B. H. et al. J. Am.Chem. Soc. 2004, 126, 8352. (c) Lipshutz, B. H. et al. Org. Lett. 2006, 8, 1963. (10) Lee, D.et al. Angew. Chem., Int. Ed. 2006, 45, 2785. (11) Baratta, W.; et al. Angew., Chem., Int.Ed. 2007, 46, 7651. (12)(a) Lopez, F. et al. Angew. Chem.; Int. Ed. 2005, 44, 2752.


Solvias®Lig

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(b) Des Mazery, R. M. et al. J. Am. Chem. Soc. 2005, 127, 9966. (c) Howell, G. P. et al.J. Am. Chem. Soc. 2006, 128, 14977. (d) Feringa, B. L. et al. Proc. N. Y. Acad. Sci. 2004,101, 5834. (13)(a) Lautens, M. K. et al. Acc. Chem. Res. 2003, 36, 48; (b) Lautens, M.;Fagnou, K. Proc. N. Y. Acad. Sci. 2004, 101, 5455. (c) Solvias AG, unpublished results.(14) Bercot, E. A.; Rovis, T. J. Am. Chem. Soc. 2004, 126, 10248. (15) Lormann, M. E. P.et al. J. Organomet. Chem. 2006, 691, 2159. (16)(a) Shen, Q.; Hartwig, J. F. J. Am. Chem.Soc. 2006, 128, 10028. (b) Fernandez-Rodriguez, M. A. Q. et al. J. Am. Chem. Soc. 2006,128, 2180. (c) Limmert, M. E. et al. J. Org. Chem. 2005, 70, 9364.

J001-188717 FeP

P

CH3

J001-288718

Fe

H3CP

P

J002-188719

FeP

P

CH3

H3C

H3C CH3

CH3CH3

CH3

J004-188723

FePP

CH3

J004-288724 Fe P

P

H3C

J005-188725

PP

CH3

H3CCH3

CH3

CH3Fe

J007-188729

FePP

CH3

CH3H3CO

H3C

H3C

H3COCH3

J007-288730

PP

H3C Fe

H3C

CH3

CH3

H3C OCH3

OCH3

J013-188737

PP

CH3Fe

H3CCH3

H3C

CH3

CH3

CH3

H3CO

H3CO

CH3

H3C

H3C

CH3

NN O

NHtBu

OHC

O

O

COOMeNHN

O

O

O

F

FF

NH2

N

O

N

NN

CF3

N

OMe

N

Rh / J002-1; 97% ee TON 1000; TOF 450 h-1

pilot process, >200 kgLonza [6]

Ru / J001-1; 90% ee TON 2000; TOF 200 h-1

medium scale productionFirmenich [6]

Rh / J002-1; 99% de TON 2000; TOF n.a.

medium scale productionLonza [6]

Rh / J002-1, 94% eeTON 350; TOF ~50 h-1

multi tons/year Merck [7]

Ir / J013-1; 90% ee TON 1500; TOF n.a.

pilot processLonza [6]

. H3PO4

Ir / J005-1; 80% eeTON 2,000,000; TOF > 400,000 h-1

very large scale productionCiba-Geigy/Solvias [2,5]

H3CO

Figure 1

R'

RX

R'

RX

Cu / J001

tolueneX = NO2, COMe, CN 80 - 99% ee

60 - >90%

0.1 - 3 mol%

+ PMHS [8-10]

Figure 2

R'

O

RR'

OH

R

NR

NH2

Ru(Josiphos, RPyme)Cl2

0.05 mol%

[11]i-PrOH / i-PrOK 60 °C, 5-30 min

95 - >99% ee 95 - 99% cv

RPyme

Figure 3

R

RO

H

H

COOH

Ph

RCOOMe R

COOMeR'

O

OHNu

R

R

R

O

O

OH

H

OX

CN

O

CNX = I, Br, OTf

R

R'MgBrCu / Josiphos

t-BuOMe-75 °C, 1-2 h

+

0.5 - 2.5 mol%

75-99%86-97% ee

[25a]

+ Rh/J001

THF, 80 °C

NuH

NuH = ROH, N-nucleophiles 93 - >99% ee

5% Pd/J001

THF, 80 °C

70-95%up to 97% ee

+ Ph2Zn

10% Pd/J001

DMF, 65-90 °C

80-92%60-94% ee

cyclic and acyclic

[27]

[28]

[30]

Figure 4

(R)-1-[(SP)-2-(Diphenylphosphino)ferrocenyl]ethyldicyclo-hexylphosphine

(R)-(S)-Josiphos; (2R)-1-[(1R)-1-(Dicyclohexyl-phosphino)ethyl]-2-(diphenylphosphino)ferrocene (acc to CAS); Josiphos SL-J001-1[155806‑35‑2]C36H44FeP2 · C2H5OHFW 640.60

P

Fe

H

CH3

P

≥97.0% (CHN)

88717-100MG 100 mg

88717-500MG 500 mg

88717-1G 1 g

88717-5G 5 g

(S)-1-[(RP)-2-(Diphenylphosphino)ferrocenyl]ethyldicyclo-hexylphosphine

(S)-(R)-Josiphos; (2S)-1-[(1S)-1-(Dicyclohexyl-phosphino)ethyl]-2-(diphenylphosphino)ferrocene (acc to CAS); Josiphos SL-J001-2[162291‑02‑3]C36H44FeP2 · C2H5OHFW 640.60

P

Fe

H

CH3P

≥97.0% (CHN)

88718-100MG 100 mg

88718-500MG 500 mg

88718-1G 1 g

88718-5G 5 g


Solvias®

LigandPortfo

lio










(R)-1-[(SP)-2-(Diphenylphosphino)ferrocenyl]ethyldi-tert-butylphosphine, ≥97.0% (CHN)

(2R)-1-[(1R)-1-[Bis(1,1-dimethylethyl)phosphino]ethyl]-2-(diphenylphosphino)ferrocene (acc to CAS); Josiphos SL-J002-1[155830‑69‑6]C32H40FeP2FW 542.45

P

Fe

H

CH3

PCH3

CH3H3CH3C

CH3

CH3

88719-100MG 100 mg

88719-500MG 500 mg

88719-1G 1 g

88719-5G 5 g

(S)-1-[(RP)-2-(Diphenylphosphino)ferrocenyl]ethyldi-tert-butylphosphine, ≥97.0% (CHN)

(2S)-1-[(1S)-1-[Bis(1,1-dimethylethyl)phosphino]ethyl]-2-(diphenylphosphino)ferrocene (acc to CAS); Josiphos SL-J002-2[277306‑29‑3]C32H40FeP2FW 542.45

P

Fe

H

CH3P

H3C

H3C CH3

CH3

H3CH3C

88720-100MG 100 mg

88720-500MG 500 mg

88720-1G 1 g

88720-5G 5 g

(R)-1-[(SP)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldicyclo-hexylphosphine, ≥97.0% (CHN)

(1R)-1-(Dicyclohexylphosphino)-2-[(1R)-1-(dicyclohexylphosphino)ethyl]ferrocene (acc toCAS); Josiphos SL-J003-1[167416‑28‑6]C36H56FeP2FW 606.62

P

Fe

H

CH3

P

88721-100MG 100 mg

88721-500MG 500 mg

88721-1G 1 g

88721-5G 5 g

(S)-1-[(RP)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldicyclo-hexylphosphine, ≥97.0% (CHN)

(1S)-1-(Dicyclohexylphosphino)-2-[(1S)-1-(dicyclohexylphosphino)ethyl]ferrocene (acc toCAS); Josiphos SL-J003-2[246231‑77‑6]C36H56FeP2FW 606.62

P

Fe

H

CH3P

88722-100MG 100 mg

88722-500MG 500 mg

88722-1G 1 g

88722-5G 5 g

(R)-1-[(SP)-2-(Dicyclohexylphosphino)ferrocenylethyl]diphenylphosphine

(1R)-1-(Dicyclohexylphosphino)-2-[(1R)-1-(diphenylphosphino)ethyl]ferrocene (acc toCAS); Josiphos SL-J004-1[158923‑09‑2]C36H44FeP2FW 594.53

P

Fe

H

CH3

P

≥97.0% (CHN)

88723-100MG 100 mg

88723-500MG 500 mg

88723-1G 1 g

88723-5G 5 g

(S)-1-[(RP)-2-(Dicyclohexylphosphino)ferrocenyl]ethyl-diphenylphosphine, ≥97.0% (CHN)

(1S)-1-(Dicyclohexylphosphino)-2-[(1S)-1-(diphenylphosphino)ethyl]ferrocene (acc toCAS); Josiphos SL-J004-2[162291‑01‑2]C36H44FeP2FW 594.53

P

Fe

H

CH3P

88724-100MG 100 mg

88724-500MG 500 mg

88724-1G 1 g

88724-5G 5 g

(R)-1-[(SP)-2-(Diphenylphosphino)ferrocenyl]ethyldi(3,5‑xyl-yl)phosphine, ≥97.0% (CHN)

P

Fe

H

CH3

P

H3C CH3

CH3

CH3

(2R)-1-[(1R)-1-[Bis(3,5‑dimethylphenyl)phosphino]ethyl]-2-(diphenylphos-phino)ferrocene (acc to CAS); Josiphos SL-J005‑1[184095‑69‑0]C40H40FeP2FW 638.54

88725-100MG 100 mg

88725-500MG 500 mg

88725-1G 1 g

88725-5G 5 g

(S)-1-[(RP)-2-(Diphenylphosphino)ferrocenyl]ethyldi(3,5‑xyl-yl)phosphine, ≥97.0% (CHN)

P

Fe

H

CH3P

CH3H3C

H3C

CH3

(2S)-1-[(1S)-1-[Bis(3,5‑dimethylphenyl)phosphino]ethyl]-2-(diphenylphos-phino)ferrocene (acc to CAS); Josiphos SL-J005‑2[223121‑07‑1]C40H40FeP2FW 638.54

88726-100MG 100 mg

88726-500MG 500 mg

88726-1G 1 g

88726-5G 5 g


Solvias®Lig

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lio


































(R)-1-{(SP)-2-[Bis[3,5‑bis(trifluoromethyl)phenyl]phosphino]ferrocenyl}ethyldicyclohexylphosphine, ≥97.0% (19F-NMR)

P

Fe

H

CH3

P

CF3

F3CF3C

CF3

(1R)-1-[Bis[3,5‑bis(trifluoromethyl)phenyl]phosphino]-2-[(1R)-1-(dicyclo-hexylphosphino)ethyl]ferrocene (acc to CAS); Josiphos SL-J006‑1[292638‑88‑1]C40H40F12FeP2FW 866.52

88727-100MG 100 mg

88727-500MG 500 mg

88727-1G 1 g

88727-5G 5 g

(S)-1-{(RP)-2-[Bis[3,5‑bis(trifluoromethyl)phenyl]phosphino]-ferrocenyl}ethyldicyclohexylphosphine, ≥97.0% (19F-NMR)

P

Fe

H

CH3P

CF3

CF3

CF3

CF3

(1S)-1-[Bis[3,5‑bis(trifluoromethyl)phenyl]phosphino]-2-[(1S)-1-(dicyclo-hexylphosphino)ethyl]ferrocene (acc to CAS); Josiphos SL-J006‑2[849923‑15‑5]C40H40F12FeP2FW 866.52

88728-100MG 100 mg

88728-500MG 500 mg

88728-1G 1 g

88728-5G 5 g

(R)-1-{(SP)-2-[Bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]ferrocenyl}ethyldicyclohexylphosphine, ≥97.0% (CHN)

P

Fe

H

CH3

P

CH3

H3CH3C

CH3

H3CO

H3CO

(1R)-1-[Bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]-2-[(1R)-1-(dicyclo-hexylphosphino)ethyl]ferrocene (acc to CAS); Josiphos SL-J007‑1[360048‑63‑1]C42H56FeO2P2FW 710.69

88729-100MG 100 mg

88729-500MG 500 mg

88729-1G 1 g

88729-5G 5 g

(S)-1-{(RP)-2-[Bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]ferrocenyl}ethyldicyclohexylphosphine, ≥97.0% (CHN)

P

Fe

H

CH3P

CH3

CH3

CH3

CH3

OCH3

OCH3

(1S)-1-[Bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]-2-[(1S)-1-(dicyclo-hexylphosphino)ethyl]ferrocene (acc to CAS); Josiphos SL-J007‑2[849923‑88‑2]C42H56FeO2P2FW 710.69

88730-100MG 100 mg

88730-500MG 500 mg

88730-1G 1 g

88730-5G 5 g

(R)-1-{(SP)-2-[Bis[3,5‑bis(trifluoromethyl)phenyl]phosphino]ferrocenyl}ethyldi(3,5‑xylyl)phosphine

P

Fe

H

CH3

P

CF3

F3CF3C

CF3

H3C CH3

CH3

CH3

(1R)-1-[Bis[3,5‑bis(trifluoromethyl)phenyl]phosphino]-2-[(1R)-1-[bis(3,5‑dimethylphenyl)phosphino]ethyl]ferrocene (acc to CAS); JosiphosSL-J008‑1[166172‑63‑0]C44H36F12FeP2FW 910.53≥97.0% (19F-NMR)

88731-100MG 100 mg

88731-500MG 500 mg

88731-1G 1 g

88731-5G 5 g

(S)-1-{(RP)-2-[Bis[3,5‑bis(trifluoromethyl)phenyl]phosphino]ferrocenyl}ethyldi(3,5‑xylyl)phosphine, ≥97.0% (19F-NMR)

P

Fe

H

CH3P

CF3

CF3

CF3

CF3

CH3H3C

H3C

CH3

(1S)-1-[Bis[3,5‑bis(trifluoromethyl)phenyl]phosphino]-2-[(1S)-1-[bis(3,5‑dimethylphenyl)phosphino]ethyl]ferrocene (acc to CAS); JosiphosSL-J008‑2C44H36F12FeP2FW 910.53

88732-100MG 100 mg

88732-500MG 500 mg

88732-1G 1 g

88732-5G 5 g


Solvias®

LigandPortfo

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(R)-1-[(SP)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldi-tert-butylphosphine, ≥97.0% (CHN)

(2R)-1-[(1R)-1-[Bis(1,1-dimethylethyl)phosphino]ethyl]-2-(dicyclohexylphosphino)ferrocene (acc to CAS); Josiphos SL-J009-1[158923‑11‑6]C32H52FeP2FW 554.55

P

Fe

H

CH3

PCH3

CH3H3CH3C

CH3

CH3

88733-100MG 100 mg

88733-500MG 500 mg

88733-1G 1 g

88733-5G 5 g

(S)-1-[(RP)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldi-tert-butylphosphine, ≥97.0% (CHN)

(2S)-1-[(1S)-1-[Bis(1,1-dimethylethyl)phosphino]ethyl]-2-(dicyclohexylphosphino)ferrocene (acc to CAS); Josiphos SL-J009-2C32H52FeP2FW 554.55

P

Fe

H

CH3P

H3C

H3C CH3

CH3

H3CH3C

88734-100MG 100 mg

88734-500MG 500 mg

88734-1G 1 g

88734-5G 5 g

(R)-1-{(SP)-2-[Bis[4-(trifluoromethyl)phenyl]phosphino]ferro-cenyl}ethyldi-tert-butylphosphine, ≥97.0% (19F-NMR)

P

Fe

H

CH3

PCH3

CH3H3CH3C

CH3

CH3

F3C

F3C

(2R)-1-[(1R)-1-[Bis(1,1‑dimethylethyl)phosphino]ethyl]-2-[bis[4-(trifluoro-methyl)phenyl]phosphino]ferrocene (acc to CAS); Josiphos SL-J011‑1[246231‑79‑8]C34H38F6FeP2FW 678.45

88735-100MG 100 mg

88735-500MG 500 mg

88735-1G 1 g

88735-5G 5 g

(S)-1-{(RP)-2-[Bis[4-(trifluoromethyl)phenyl]phosphino]ferro-cenyl}ethyldi-tert-butylphosphine, ≥97.0% (19F-NMR)

P

Fe

H

CH3P

H3C

H3C CH3

CH3

H3CH3C

CF3

CF3

(2S)-1-[(1S)-1-[Bis(1,1‑dimethylethyl)phosphino]ethyl]-2-[bis[4-(trifluoro-methyl)phenyl]phosphino]ferrocene (acc to CAS); Josiphos SL-J011‑2[849924‑37‑4]C34H38F6FeP2FW 678.45

88736-100MG 100 mg

88736-500MG 500 mg

88736-1G 1 g

88736-5G 5 g

(R)-1-[(SP)-2-[Bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]ferrocenyl}ethyldi-tert-butylphosphine, ≥97.0% (CHN)

P

Fe

H

CH3

PCH3

CH3H3CH3C

CH3

CH3

H3CO

H3CO

H3C

CH3

H3C

CH3

(2R)-1-[(1R)-1-[Bis(1,1‑dimethylethyl)phosphino]ethyl]-2-[bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]ferrocene (acc to CAS); Josiphos SL-J013‑1[187733‑50‑2]C38H52FeO2P2FW 658.61

88737-100MG 100 mg

88737-500MG 500 mg

88737-1G 1 g

88737-5G 5 g

(S)-1-[(RP)-2-[Bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]ferrocenyl}ethyldi-tert-butylphosphine, ≥97.0% (CHN)

P

Fe

H

CH3P

H3C

H3C CH3

CH3

H3CH3C

OCH3

OCH3

CH3

CH3

CH3

CH3

(2S)-1-[(1S)-1-[Bis(1,1‑dimethylethyl)phosphino]ethyl]-2-[bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]ferrocene (acc to CAS); Josiphos SL-J013‑2[849924‑40‑9]C38H52FeO2P2FW 658.61

88738-100MG 100 mg

88738-500MG 500 mg

88738-1G 1 g

88738-5G 5 g

(R)-1-{(SP)-2-[Di(2‑furyl)phosphino]ferrocenyl}ethyldi(3,5‑xyl-yl)phosphine, ≥97.0% (CHN)

P

Fe

H

CH3

P

H3C CH3

CH3

CH3

O

O

(2R)-1-[(1R)-1-[Bis(3,5‑dimethylphenyl)phosphino]ethyl]-2-(di-2‑furanyl-phosphino)ferrocene (acc to CAS); Josiphos SL-J015‑1[649559‑65‑9]C36H36FeO2P2FW 618.46

88739-100MG 100 mg

88739-500MG 500 mg

88739-1G 1 g

88739-5G 5 g


Solvias®Lig

andPortfo

lio






























(S)-1-{(RP)-2-[Di(2‑furyl)phosphino]ferrocenyl}ethyldi(3,5‑xyl-yl)phosphine, ≥97.0% (CHN)

P

Fe

H

H3CP

CH3H3C

H3C

CH3

O

O

(2S)-1-[(1S)-1-[Bis(3,5‑dimethylphenyl)phosphino]ethyl]-2-(di-2‑furanyl-phosphino)ferrocene (acc to CAS); Josiphos SL-J015‑2[649559‑66‑0]C36H36FeO2P2FW 618.46

88740-100MG 100 mg

88740-500MG 500 mg

88740-1G 1 g

88740-5G 5 g

(R)-1-{(SP)-2-[Di(2‑furyl)phosphino]ferrocenyl}ethyldi-tert-butylphosphine, ≥97.0% (CHN)

(2R)-1-[(1R)-1-[Bis(1,1-dimethylethyl)phosphino]ethyl]-2-(di-2-furanylphosphino)ferrocene (acc to CAS); Josiphos SL-J212-1[849924‑41‑0]C28H36FeO2P2FW 522.38

P

Fe

H

CH3CH3

CH3H3CH3C

CH3

CH3PO

O

88741-100MG 100 mg

88741-500MG 500 mg

88741-1G 1 g

88741-5G 5 g

(S)-1-{(RP)-2-[Di(2‑furyl)phosphino]ferrocenyl}ethyldi-tert-butylphosphine, ≥97.0% (CHN)

(2S)-1-[(1S)-1-[Bis(1,1-dimethylethyl)phosphino]ethyl]-2-(di-2-furanylphosphino)ferrocene (acc to CAS); Josiphos SL-J212-2[849924‑42‑1]C28H36FeO2P2FW 522.38

P

Fe

H

H3CH3C

H3C CH3

CH3

H3CH3C

P O

O

88742-100MG 100 mg

88742-500MG 500 mg

88742-1G 1 g

88742-5G 5 g

(R)-1-{(SP)-2-[Di(1‑naphthyl)phosphino]ferrocenyl}ethyldi-tert-butylphosphine, ≥97.0% (CHN)

P

Fe

H

CH3

PCH3

CH3H3CH3C

CH3

CH3

(2R)-1-[(1R)-1-[Bis(1,1‑dimethylethyl)phosphino]ethyl]-2-(di-1‑naph-thalenylphosphino)ferrocene (acc to CAS); Josiphos SL-J216‑1[849924‑43‑2]C40H44FeP2FW 642.57

88743-100MG 100 mg

88743-500MG 500 mg

88743-1G 1 g

88743-5G 5 g

(S)-1-{(RP)-2-[Di(1‑naphthyl)phosphino]ferrocenyl}ethyldi-tert-butylphosphine, ≥97.0% (CHN)

P

Fe

H

CH3

PH3C

H3C CH3

CH3

H3CH3C

(2S)-1-[(1S)-1-[Bis(1,1‑dimethylethyl)phosphino]ethyl]-2-(di-1‑naph-thalenylphosphino)ferrocene (acc to CAS); Josiphos SL-J216‑2[849924‑44‑3]C40H44FeP2FW 642.57

88744-100MG 100 mg

88744-500MG 500 mg

88744-1G 1 g

88744-5G 5 g

(R)-1-{(SP)-2-[Di(1‑naphthyl)phosphino]ferrocenyl}ethyldi(3,5‑xylyl)phosphine, ≥97.0% (CHN)

P

Fe

H

CH3

P

H3C CH3

CH3

CH3

(2R)-1-[(1R)-1-[Bis(3,5‑dimethylphenyl)phosphino]ethyl]-2-(di-1‑naph-thalenylphosphino)ferrocene (acc to CAS); Josiphos SL-J404‑1[851308‑40‑2]C48H44FeP2FW 738.66

88745-100MG 100 mg

88745-500MG 500 mg

88745-1G 1 g

88745-5G 5 g

(S)-1-{(RP)-2-[Di(1‑naphthyl)phosphino]ferrocenyl}ethyldi(3,5‑xylyl)phosphine, ≥97.0% (CHN)

P

Fe

H

H3CP

CH3H3C

H3C

CH3

(2S)-1-[(1S)-1-[Bis(3,5‑dimethylphenyl)phosphino]ethyl]-2-(di-1‑naph-thalenylphosphino)ferrocene (acc to CAS); Josiphos SL-J404‑2[851308‑41‑3]C48H44FeP2FW 738.66

88746-100MG 100 mg

88746-500MG 500 mg

88746-1G 1 g

88746-5G 5 g


Solvias®

LigandPortfo

lio






























(R)-1-{(SP)-2-[Bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]ferrocenyl}-ethyldi(3,5‑xylyl)phosphine, ≥97.0% (CHN)

P

Fe

H

CH3

H3C CH3

CH3

CH3

P

CH3

H3CH3C

CH3

H3CO

H3CO

(2R)-1-[(1R)-1-[Bis(3,5‑dimethylphenyl)phosphino]ethyl]-2-[bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]ferrocene (acc to CAS);Josiphos SL-J418‑1[849924‑45‑4]C46H52FeO2P2FW 754.70

88747-100MG 100 mg

88747-500MG 500 mg

88747-1G 1 g

88747-5G 5 g

(S)-1-{(RP)-2-[Bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]ferrocenyl}-ethyldi(3,5‑xylyl)phosphine, ≥97.0% (CHN)

P

Fe

H

H3C

CH3H3C

H3C

CH3

P

CH3

CH3

CH3

CH3

OCH3

OCH3

(2S)-1-[(1S)-1-[Bis(3,5‑dimethylphenyl)phosphino]ethyl]-2-[bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]ferrocene (acc to CAS);Josiphos SL-J418‑2[849924‑48‑7]C46H52FeO2P2FW 754.70

88748-100MG 100 mg

88748-500MG 500 mg

88748-1G 1 g

88748-5G 5 g

(R)-1-{(SP)-2-[Bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]ferrocenyl}-ethylbis(2‑methylphenyl)phosphine

P

Fe

H

CH3

P

CH3

H3CH3C

CH3

H3CO

H3CO H3C CH3

(1R)-1-[Bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]-2-[(1R)-1-[bis(2‑methylphenyl)phosphino]ethyl]ferrocene (acc to CAS); Josiphos SL-J425‑1[849924‑49‑8]C44H48FeO2P2FW 726.64≥97.0% (CHN)

88749-100MG 100 mg

88749-500MG 500 mg

88749-1G 1 g

88749-5G 5 g

(S)-1-{(RP)-2-[Bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]ferrocenyl}-ethylbis(2‑methylphenyl)phosphine, ≥97.0%(CHN)

P

Fe

H

H3CP

CH3

CH3

CH3

CH3

OCH3

OCH3CH3CH3

(1S)-1-[Bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]-2-[(1S)-1-[bis(2‑methylphenyl)phosphino]ethyl]ferrocene (acc to CAS); Josiphos SL-J425‑2[849924‑52‑3]C44H48FeO2P2FW 726.64

88750-100MG 100 mg

88750-500MG 500 mg

88750-1G 1 g

88750-5G 5 g

(R)-1-{(SP)-2-[Di(2‑furyl)phosphino]ferrocenyl}ethylbis(2‑methylphenyl)phosphine, ≥97.0% (CHN)

(2R)-1-[(1R)-1-[Bis(2-methylphenyl)phosphino]ethyl]-2-(di-2-furanylphosphino)ferrocene (accto CAS); Josiphos SL-J452-1[849924‑73‑8]C34H32FeO2P2FW 590.41

P

Fe

H

CH3

PO

O

H3CCH3

88751-100MG 100 mg

88751-500MG 500 mg

88751-1G 1 g

88751-5G 5 g

(S)-1-{(RP)-2-[Di(2‑furyl)phosphino]ferrocenyl}ethylbis(2‑methylphenyl)phosphine, ≥97.0% (CHN)

(2S)-1-[(1S)-1-[Bis(2-methylphenyl)phosphino]ethyl]-2-(di-2-furanylphosphino)ferrocene (accto CAS); Josiphos SL-J452-2[849924‑74‑9]C34H32FeO2P2FW 590.41

P

Fe

H

H3CP O

O

CH3CH3

88752-100MG 100 mg

88752-500MG 500 mg

88752-1G 1 g

88752-5G 5 g

(R)-1-[(SP)-2-(Di-tert-butylphosphino)ferrocenyl]ethyl-diphenylphosphine, ≥97.0% (CHN)

(1R)-1-[Bis(1,1-dimethylethyl)phosphino]-2-[(1R)-1-(diphenylphosphino)ethyl]ferrocene(acc to CAS); Josiphos SL-J502-1[223120‑71‑6]C32H40FeP2FW 542.45

P

Fe

H

CH3

PH3C

CH3H3C

H3CCH3H3C

88753-100MG 100 mg

88753-500MG 500 mg

88753-1G 1 g

88753-5G 5 g


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(S)-1-[(RP)-2-(Di-tert-butylphosphino)ferrocenyl]ethyl-diphenylphosphine, ≥97.0% (CHN)

(1S)-1-[Bis(1,1-dimethylethyl)phosphino]-2-[(1S)-1-(diphenylphosphino)ethyl]ferrocene(acc to CAS); Josiphos SL-J502-2[223121‑01‑5]C32H40FeP2FW 542.45

P

Fe

H

H3CP CH3

CH3CH3

CH3

H3C CH3

88754-100MG 100 mg

88754-500MG 500 mg

88754-1G 1 g

88754-5G 5 g

(R)-1-[(SP)-2-(Di-tert-butylphosphino)ferrocenyl]ethylbis(2‑methylphenyl)phosphine, ≥97.0% (CHN)

(1R)-1-[Bis(1,1-dimethylethyl)phosphino]-2-[(1R)-1-[bis(2-methylphenyl)phosphino]ethyl]ferrocene (acc to CAS); Josiphos SL-J505-1[849924‑76‑1]C34H44FeP2FW 570.51

P

Fe

H

CH3

PH3C

CH3H3C

H3CCH3H3C

H3C CH3

88755-100MG 100 mg

88755-500MG 500 mg

88755-1G 1 g

88755-5G 5 g

(S)-1-[(RP)-2-(Di-tert-butylphosphino)ferrocenyl]ethylbis(2‑methylphenyl)phosphine, ≥97.0% (CHN)

(1S)-1-[Bis(1,1-dimethylethyl)phosphino]-2-[(1S)-1-[bis(2-methylphenyl)phosphino]ethyl]ferrocene (acc to CAS); Josiphos SL-J505-2[849924‑77‑2]C34H44FeP2FW 570.51

P

Fe

H

H3CP CH3

CH3CH3

CH3

H3C CH3

CH3CH3

88756-100MG 100 mg

88756-500MG 500 mg

88756-1G 1 g

88756-5G 5 g

WalphosLike Josiphos, Walphos ligands are modular but form 8‑memberedmetallocycles due to the additional phenyl ring attached to thecyclopentadiene ring.1 There are noticeable electronic effects but thescope of this ligand family is still under investigation; several derivativesare available from Solvias on a research scale. Walphos ligands showpromise for various enantioselective hydrogenations and pertinentexamples are depicted in Figure 1. Rh/Walphos catalysts gave goodresults for dehydro amino and itaconic acid derivatives1–3 (ee 92–95%,preferred ligands W001, W002, W004, W006 and W009) and of vinylboronates4 (see Figure 1). Ru/Walphos complexes were highly selectivefor β-keto esters (ee 91‑95%, W001, W002, W003 and W005) andacetyl acetone (ee >99.5%, s/c 1000, W001).2,3 Recently, two noveltransformations were reported to be catalyzed by Rh/Walphos complexeswith high enantioselectivities (Figure 1): the 4+2‑addition of 4‑alkynalswith an acryl amide by Tanaka and co-workers5 and the reductivecoupling of enynes with α-keto esters by Krische's group.6

The first industrial application has just been realized in collaboration withSpeedel/Novartis for the hydrogenation of SPP100‑SyA, a stericallydemanding α,β-unsaturated acid intermediate of the renin inhibitorSPP100.2 The process has already been operated on a multiton scale.Lilly's chemists7 developed a process of a PPAR agonist using theRh-catalyzed asymmetric hydrogenation of (Z)-cinnamic acid as key step.A screen of over 250 catalysts and conditions revealed Rh-W001 as themost effective ligand, giving the product in 92% ee.

References: (1) Sturm, T. et al. Chimia 2001, 55, 688. (2) Sturm, T. et al. Adv. Synth. Catal.2003, 345, 160. (3) Solvias AG, unpublished screening results. (4)(a) Morgan, J. B.; Morken,J. P. J. Am. Chem. Soc. 2004, 126, 15338. (b) Moran, W. J.; Morken, J. P. Org. Lett. 2006, 6,2413. (5) Tanaka, K. et al. Angew. Chem., Int. Ed. 2005, 44, 7260. (6) Kong, J-R. et al. J.Am. Chem. Soc. 2006, 128, 718. (7) Houpis, I. N. et al. Org. Lett. 2005, 7, 1947.

W001-165671

CH3

PP

F3C CF3

CF3

CF3Fe

W001-265672

H3C

PP

CF3F3C

F3C

F3C Fe

W002-165673

CH3

PP

Fe

W002-265674

H3C

P

P

Fe

W003-165675

CH3

PP

Fe

W003-265676

H3C

P

P

Fe

W005-165677

CH3

PP

F3C CF3

CF3

CF3

CH3

OCH3H3C

H3C

H3CO

H3CFe

W005-265678

H3C

P P

CF3F3C

F3C

F3C

H3C

H3CO CH3

CH3

OCH3

CH3Fe

W008-165681

CH3

PP

F3C CF3

CF3

CF3Fe

W008-265682

H3C

P P

CF3F3C

F3C

F3C Fe

W009-165683

H3C

P P

CH3H3C

H3C

H3C

CH3

CH3

CH3

H3C

Fe

W009-265684

H3C

P P

CH3H3C

H3C

H3C

CH3

CH3

CH3

H3C

Fe

H

O

R

R

BOO

O

O

O

OH

O

R

BOO

CONMe2

R H

O

CONMe2

R COOMe

OR

COOMe

OH

OEt

CO2H

BnO

Rh / W001 or W008

Rh / Walphos W001, 95% ee TON 5000; TOF ~800 h-1

medium scale productionNovartis / Solvias [2]

60-90%85 - >95% ee

s/c 50, 15-35 bar

+Rh / W002

s/c 10-20CH2Cl2, 80 °C

R = (subst)Ar, Alk50-90%97 - >99% ee

+Rh / W009

s/c 501 bar, 80 °C

+ H2

R = (subst)Alk 80 - 97%88 - 93% ee

+ H2

Rh / W001, 92% ee TON ~300, TOF ~20 h-1

feasibility studyLilly [7]

[4]

[5]

[6]

Figure 1


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(R)-1-{(RP)-2-[2-(Diphenylphosphino)phenyl]ferrocenyl}ethyl-bis[3,5‑bis-(trifluoromethyl)phenyl]phosphine, ≥97.0% (19F-NMR)

P

Fe

H

CH3

F3C CF3

CF3

CF3

P

(1S)-1-[(1R)-1-[Bis[3,5‑bis(trifluoromethyl)phenyl]phosphino]ethyl]-2-[2-(diphenylphosphino)phenyl]ferrocene (acc to CAS); Walphos SL-W001‑1[387868‑06‑6]C46H32F12FeP2FW 930.52

65671-100MG 100 mg

65671-500MG 500 mg

65671-1G 1 g

65671-5G 5 g

(S)-1-{(SP)-2-[2-(Diphenylphosphino)phenyl]ferrocenyl}ethyl-bis[3,5‑bis-(trifluoromethyl)phenyl]phosphine, ≥97.0% (19F-NMR)

P

Fe

H

H3C

CF3F3C

F3C

CF3

P

(1R)-1-[(1S)-1-[Bis(3,5‑bis(trifluoromethyl)phenyl)phosphino]ethyl]-2-[2-(diphenylphosphino)phenyl]ferrocene (acc to CAS); Walphos SL-W001‑2[849925‑17‑3]C46H32F12FeP2FW 930.52

65672-100MG 100 mg

65672-500MG 500 mg

65672-1G 1 g

65672-5G 5 g

(R)-1-{(RP)-2-[2-(Diphenylphosphino)phenyl]ferrocenyl}ethyl-diphenylphosphine, ≥97.0% (CHN)

(1S)-1-[(1R)-1-(Diphenylphosphino)ethyl]-2-[2-(diphenylphosphino)phenyl]ferrocene (accto CAS); Walphos SL-W002-1[388079‑58‑1]C42H36FeP2FW 658.53

P

Fe

H

CH3

P

65673-100MG 100 mg

65673-500MG 500 mg

65673-1G 1 g

65673-5G 5 g

(S)-1-{(SP)-2-[2-(Diphenylphosphino)phenyl]ferrocenyl}ethyl-diphenylphosphine, ≥97.0% (CHN)

(1R)-1-[(1S)-1-(Diphenylphosphino)ethyl]-2-[2-(diphenylphosphino)phenyl]ferrocene (accto CAS); Walphos SL-W002-2[565184‑37‑4]C42H36FeP2FW 658.53

P

Fe

H

H3C

P

65674-100MG 100 mg

65674-500MG 500 mg

65674-1G 1 g

65674-5G 5 g

(R)-1-{(RP)-2-[2-(Diphenylphosphino)phenyl]ferrocenyl}ethyl-dicyclohexylphosphine, ≥97.0% (CHN)

(1S)-1-[(1R)-1-(Dicyclohexylphosphino)ethyl]-2-[2-(diphenylphosphino)phenyl]ferrocene(acc to CAS); Walphos SL-W003-1[388079‑60‑5]C42H48FeP2FW 670.62

P

Fe

H

CH3

P

65675-100MG 100 mg

65675-500MG 500 mg

65675-1G 1 g

65675-5G 5 g

(S)-1-{(SP)-2-[2-(Diphenylphosphino)phenyl]ferrocenyl}ethyl-dicyclohexylphosphine, ≥97.0% (CHN)

(1R)-1-[(1S)-1-(Dicyclohexylphosphino)ethyl]-2-[2-(diphenylphosphino)phenyl]ferrocene(acc to CAS); Walphos SL-W003-2[849925‑19‑5]C42H48FeP2FW 670.62

P

Fe

H

H3C

P

65676-100MG 100 mg

65676-500MG 500 mg

65676-1G 1 g

65676-5G 5 g

(R)-1-{(RP)-2-[2-[Bis(4‑methoxy-3,5‑dimethylphenyl)phos-phino]phenyl]ferrocenyl}ethylbis[3,5‑bis(trifluoromethyl)phenyl]phosphine, ≥95.0%

PFe

H

CH3

P

F3C CF3

CF3

CF3

CH3CH3

H3CO

H3C

OCH3

CH3

(1S)-1-[(1R)-1-[Bis[3,5‑bis(trifluoromethyl)phenyl]phosphino]ethyl]-2-[2-[bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]phenyl]ferrocene (acc toCAS); Walphos SL-W005‑1[494227‑30‑4]C52H44F12FeO2P2FW 1046.68

65677-100MG 100 mg

65677-500MG 500 mg

65677-1G 1 g

65677-5G 5 g

(S)-1-{(SP)-2-[2-[Bis(4‑methoxy-3,5‑dimethylphenyl)phos-phino]phenyl]ferrocenyl}ethylbis[3,5‑bis(trifluoromethyl)phenyl]phosphine, ≥97.0%

PFe

H

H3C

P

CF3F3C

F3C

CF3

CH3 CH3

OCH3

CH3

H3CO

H3C

(1R)-1-[(1S)-1-[Bis[3,5‑bis(trifluoromethyl)phenyl]phosphino]ethyl]-2-[2-[bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]phenyl]ferrocene (acc toCAS); Walphos SL-W005‑2[849925‑20‑8]C52H44F12FeO2P2FW 1046.68

65678-100MG 100 mg

65678-500MG 500 mg

65678-1G 1 g

65678-5G 5 g


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(R)-1-{(RP)-2-[2-(Diphenylphosphino)phenyl]ferrocenyl}ethyl-di(3,5‑xylyl)phosphine, ≥97.0% (CHN)

P

Fe

H

CH3

H3C CH3

CH3

CH3

P

(1S)-1-[(1R)-1-[Bis(3,5‑dimethylphenyl)phosphino]ethyl]-2-[2-(diphenyl-phosphino)phenyl]ferrocene (acc to CAS); Walphos SL-W006‑1[494227‑31‑5]C46H44FeP2FW 714.63

65679-100MG 100 mg

65679-500MG 500 mg

65679-1G 1 g

65679-5G 5 g

(S)-1-{(SP)-2-[2-(Diphenylphosphino)phenyl]ferrocenyl}ethyl-di(3,5‑xylyl)phosphine, ≥97.0% (CHN)

P

Fe

H

H3C

CH3H3C

H3C

CH3

P

(1R)-1-[(1S)-1-[Bis(3,5‑dimethylphenyl)phosphino]ethyl]-2-[2-(diphenyl-phosphino)phenyl]ferrocene (acc to CAS); Walphos SL-W006‑2[849925‑21‑9]C46H44FeP2FW 714.63

65680-100MG 100 mg

65680-500MG 500 mg

65680-1G 1 g

65680-5G 5 g

(R)-1-{(RP)-2-[2-(Dicyclohexylphosphino)phenyl]ferrocenyl}ethylbis[3,5‑bis(trifluoromethyl)phenyl]phosphine, ≥97.0%(NMR)

P

Fe

H

CH3

F3C CF3

CF3

CF3

P

(1S)-1-[(1R)-1-[bis[3,5‑bis(trifluoromethyl)phenyl]phosphino]ethyl]-2-[2-(dicyclohexylphosphino)phenyl]ferrocene (acc to CAS); Walphos SL-W008‑1[494227‑32‑6]C46H44F12FeP2FW 942.61

65681-100MG 100 mg

65681-500MG 500 mg

65681-1G 1 g

65681-5G 5 g

(S)-1-{(SP)-2-[2-(Dicyclohexylphosphino)phenyl]ferrocenyl}ethylbis[3,5‑bis(trifluoromethyl)phenyl]phosphine, ≥97.0%(NMR)

P

Fe

H

H3C

CF3F3C

F3C

CF3

P

(1R)-1-[(1S)-1-[bis[3,5‑bis(trifluoromethyl)phenyl]phosphino]ethyl]-2-[2-(dicyclohexylphosphino)phenyl]ferrocene (acc to CAS); Walphos SL-W008‑2[849925‑22‑0]C46H44F12FeP2FW 942.61

65682-100MG 100 mg

65682-500MG 500 mg

65682-1G 1 g

65682-5G 5 g

(R)-1-{(RP)-2-[2-[Di(3,5‑xylyl)phosphino]phenyl]ferrocenyl}ethyldi(3,5‑xylyl)phosphine, ≥97.0% (CHN)

PFe

H

CH3

P

H3C CH3

CH3

CH3

CH3CH3

H3C CH3

(1S)-1-[(1R)-1-[Bis(3,5‑dimethylphenyl)phosphino]ethyl]-2-[2-[bis(3,5‑dimethylphenyl)phosphino]phenyl]ferrocene (acc to CAS); WalphosSL-W009‑1[494227‑33‑7]C50H52FeP2FW 770.74

65683-100MG 100 mg

65683-500MG 500 mg

65683-1G 1 g

65683-5G 5 g

(S)-1-{(SP)-2-[2-[Di(3,5‑xylyl)phosphino]phenyl]ferrocenyl}ethyldi(3,5‑xylyl)phosphine, ≥97.0% (CHN)

PFe

H

H3C

P

CH3H3C

H3C

CH3

CH3 CH3

CH3H3C

(1R)-1-[(1S)-1-[Bis(3,5‑dimethylphenyl)phosphino]ethyl]-2-[2-[bis(3,5‑dimethylphenyl)phosphino]phenyl]ferrocene (acc to CAS); WalphosSL-W009‑2[849925‑24‑2]C50H52FeP2FW 770.74

65684-100MG 100 mg

65684-500MG 500 mg

65684-1G 1 g

65684-5G 5 g


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(R)-1-{(RP)-2-[2-(Diphenylphosphino)phenyl]ferrocenyl}ethyl-di(2‑norbornyl)phosphine, ≥97.0% (CHN)

P

Fe

H

CH3

P

(1S)-1-[(1R)-1-[Bis(bicyclo[2.2.1]hept-2‑yl)phosphino]ethyl]-2-[2-(diphenylphosphino)phenyl]ferrocene (acc to CAS); Walphos SL-W022‑1[849925‑29‑7]C44H48FeP2FW 694.64

65685-100MG 100 mg

65685-500MG 500 mg

65685-1G 1 g

65685-5G 5 g

(S)-1-{(SP)-2-[2-(Diphenylphosphino)phenyl]ferrocenyl}ethyl-di(2‑norbornyl)phosphine, ≥97.0% (CHN)

P

Fe

H

H3C

P

(1R)-1-[(1S)-1-[Bis(bicyclo[2.2.1]hept-2‑yl)phosphino]ethyl]-2-[2-(diphenylphosphino)phenyl]ferrocene (acc to CAS); Walphos SL-W022‑2[849925‑45‑7]C44H48FeP2FW 694.64

65686-100MG 100 mg

65686-500MG 500 mg

65686-1G 1 g

65686-5G 5 g

TaniaphosCompared to Josiphos, the Taniaphos ligands developed by the Knochelgroup1 have an additional phenyl ring inserted at the side chain of theUgi amine. Besides the two-phosphine moieties, the substituent at thestereogenic center can also be varied and, up to now, three generationsof Taniaphos ligands with different substituents at the α-position havebeen prepared. Several Taniaphos ligands are being marketed by Solviasin collaboration with Umicore and selected derivatives are beingproduced on a multikilogram scale.

A variety of Taniaphos ligands are very selective in a number of modelhydrogenation reactions.1,2 Both the nature of two phosphine moieties,as well as the substituent and the configuration of the stereogenic centerat the α-position, have strong effects on the catalytic performance,sometimes even on the sense of induction. Taniaphos complexes arehighly active and stereoselective for the Rh catalyzed hydrogenation ofmethyl acetamido cinnamate (ee 94–99.5%) and dimethyl itaconate(91–99.5% ee), and in the Ru catalyzed hydrogenation of β-ketoesters(94–98% ee), cyclic β-ketoesters (85–94% ee, 99% de of anti-product,s/c up to 25,000) and 1,3‑diketones (97–99.4% ee, ~99% de of anti-product). Enamides are hydrogenated with 92–97% ee's but low TOFs(Rh/T021) and a β-dehydroacetamido acid with 99.5% (Rh/T003).

Recently, a variety of highly enantioselective transformations weredescribed using Taniaphos complexes.3,4 Selected reactions are depictedin Figure 1. T001 was found to be very selective for the Rh catalyzednucleophilic ring opening of an azabicycle.3 Cu Taniaphos complexeswere also very effective for the reductive addition of aldehydes4a tomethyl acrylate and of methyl ketones to methyl acrylate.4b

References: (1)(a) Ireland, T. et al. Angew. Chem., Int. Ed. Engl. 1999, 38, 3212. (b) Ireland,T. et al. Chem.- Eur. J. 2002, 8, 843. (c) Lotz, M. et al. Angew. Chem., Int. Ed. 2002, 41,4708. (d) Tappe, K.; Knochel, P. Tetrahedron: Asymmetry 2004, 15, 91. (2) Spindler, F. et al.Tetrahedron: Asymmetry 2004, 15, 2299. (3) Lautens, M. et al. Org. Lett. 2002, 4, 3465.(4)(a) Chuzel, O. et al. Org. Lett. 2006, 8, 5943. (b) Deschamp, J. et al. Angew. Chem., Int.Ed. 2006, 45, 1292.

T001-173475

P

FeH

NH3C

H3CP

T001-273476

P

Fe

H

NCH3

CH3P

T002-107541

P

FeH

NH3C

H3CP

T002-207542

P

Fe

H

NCH3

CH3P

NBoc

R2NNHBoc

R

O

COOMe RCOOMe

HO

RCOOMe

HO

Rh / T001+

75-90% 84-96% ee

+ + PhSiH3

Cu / Taniaphos

-40 °C

+

erythro threo

R = Alk, (subst) PhR' = H, preferred ligand T001, 50-88% erythro, ee 68-97 R' = Me, preferred ligand T002, 86-95% erythro, ee 83-95%

70-99%

[3]

[4]

R2NH

Figure 1

(RP)-1‑Dicyclohexylphosphino-2-[(R)-α-(dimethylamino)-2-(dicyclohexylphosphino)benzyl]ferrocene, ≥97.0% (CHN)

(1S)-1-(Dicyclohexylphosphino)-2-[(R)-[2-(dicyclo-hexylphosphino)phenyl](dimethylamino)methyl]ferrocene (acc to CAS); Taniaphos SL-T002-1C43H63FeNP2FW 711.76

P

FeH

NH3C

H3CP

07541-100MG 100 mg

07541-500MG 500 mg

07541-1G 1 g

07541-5G 5 g

(SP)-1‑Dicyclohexylphosphino-2-[(S)-α-(dimethylamino)-2-(dicyclohexylphosphino)benzyl]ferrocene, ≥97.0% (CHN)

(1R)-1-(Dicyclohexylphosphino)-2-[(S)-[2-(dicyclo-hexylphosphino)phenyl](dimethylamino)methyl]ferrocene (acc to CAS); Taniaphos SL-T002-2C43H63FeNP2FW 711.76

P

Fe

H

NCH3

CH3P

07542-100MG 100 mg

07542-500MG 500 mg

07542-1G 1 g

07542-5G 5 g


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(RP)-1-[(R)-α-(Dimethylamino)-2-(diphenylphosphino)ben-zyl]-2‑diphenylphosphinoferrocene, ≥97.0% (CHN)

(2S)-1-[(R)-(Dimethylamino)[2-(diphenylphos-phino)phenyl]methyl]-2-(diphenylphosphino)ferrocene (acc to CAS); Taniaphos SL-T001-1C43H39FeNP2FW 687.57

P

FeH

NH3C

H3CP

73475-100MG 100 mg

73475-500MG 500 mg

73475-1G 1 g

73475-5G 5 g

(SP)-1-[(S)-α-(Dimethylamino)-2-(diphenylphosphino)benzyl]-2‑diphenylphosphinoferrocene, ≥97.0% (CHN)

(2R)-1-[(S)-(Dimethylamino)[2-(diphenylphos-phino)phenyl]methyl]-2-(diphenylphosphino)ferrocene (acc to CAS); Taniaphos SL-T001-2C43H39FeNP2FW 687.57

P

Fe

H

NCH3

CH3P

73476-100MG 100 mg

73476-500MG 500 mg

73476-1G 1 g

73476-5G 5 g

Mandyphos (Ferriphos)Ferriphos was first prepared by Ito and coworkers1 as a bidentate analogof PPFA. In 1998, Knochel2 developed a general synthesis for a highlymodular ligand family which was later called Mandyphos in which notonly the PR'2 moieties but also the substituents at the side chain can beused for fine tuning purposes. Selected Mandyphos derivatives arecommercialized by Solvias in collaboration with Umicore. Even thoughthe scope of this family is not yet fully explored, screening results3

indicate high enantioselectivities as well as high activity for severalMandyphos derivatives in the Rh catalyzed hydrogenation ofdehydroamino acid derivatives (preferred ligand M004, 95 – >99% ee,s/c up to 20,000) and the Ru catalyzed hydrogenation of tiglic acid(M004, 97% ee). M004 was also the ligand of choice for the Rhcatalyzed hydrogenation of various methyl 2‑furyl acrylates4 whileRh/Ferriphos was highly selective for Rh catalyzed ring opening ofazabicycles with amines5 (see Figure 1). Several Mandyphos derivativesare being produced on a multikilogram scale.

References: (1) Sawamura, M. et al. Tetrahedron: Asymmetry 1991, 2, 593. (2)(a) AlmenaPerea, J. et al. Tetrahedron Lett. 1998, 39, 8073. (b) Lotz, M. et al. Tetrahedron: Asymmetry1999, 10, 1839. (c) Almena Perea, J. et al. Tetrahedron: Asymmetry 1999, 10, 375.(3) Spindler, F. et al. Tetrahedron: Asymmetry 2004, 15, 2299. (4) Hashmi, A. S. K. et al.Chem. -Eur. J. 2006, 12, 5376. (5) Cho, Y-h. et al. J. Am. Chem. Soc. 2006, 128, 6837.

M001-173463

PN

PNCH3H3C

CH3

H3C

Fe M001-273464

PN

P NH3C CH3

H3CCH3

Fe

M004-173469

PN

PNCH3

H3C

CH3

H3C

Fe

CH3H3CCH3

CH3

H3C

H3C

H3C CH3

OCH3

OCH3

H3CO

OCH3

M004-273470

PN

P NH3C CH3

H3C

CH3

Fe

H3C CH3

H3C

H3C

CH3

CH3

CH3H3C

H3CO

OCH3

OCH3

OCH3

O NHCbz

COOMeR

BocN

R

R

R2NBocHN

R

R

+ R2NH

R = H, Me, Et, OSiR3, CF3 ee 80-97%, yield 80-97%

Rh / M001

80 - >95%94 - >99% ee

R = H, MeR' = H, Me, MeO, F

[Rh(nbd)2]BF4 / M004; 5 bar, rt

[4]

[5]

Figure 1

(SP,S′P)-1,1′-Bis[(R)-α-(dimethylamino)benzyl]-2,2′-bis(diphenylphosphino)ferrocene, ≥97.0% (CHN)

(2R,2′R)-1,1′-Bis[(R)-(dimethylamino)phenyl-methyl]-2,2′-bis(diphenylphosphino)ferrocene(acc to CAS); Mandyphos SL-M001-1C52H50FeN2P2FW 820.76

Fe

N

CH3H3C

P

H

NH3C

H3C

P

H

73463-100MG 100 mg

73463-500MG 500 mg

73463-1G 1 g

73463-5G 5 g

(RP,R′P)-1,1′-Bis[(S)-α-(dimethylamino)benzyl]-2,2′-bis(diphenylphosphino)ferrocene, ≥97.0% (CHN)

(2S,2′S)-1,1′-Bis[(S)-(dimethylamino)phenyl-methyl]-2,2′-bis(diphenylphosphino)ferrocene(acc to CAS); Mandyphos SL-M001-2[223725‑09‑5]C52H50FeN2P2FW 820.76

Fe

N

H3C CH3

P

H

NCH3

CH3

P

H

73464-100MG 100 mg

73464-500MG 500 mg

73464-1G 1 g

73464-5G 5 g

(SP,S′P)-1,1′-Bis(dicyclohexylphosphino)-2,2′-bis[(R)-α-(dimethylamino)benzyl]ferrocene, ≥97.0% (CHN)

(1R,1′R′)-1,1′-Bis(dicyclohexylphosphino)-2,2′-bis[(R)-(dimethylamino)phenylmethyl]ferrocene(acc to CAS); Mandyphos SL-M002-1[494227‑35‑9]C52H74FeN2P2FW 844.95

Fe

N

CH3H3C

P

H

NH3C

H3C

P

H

73465-100MG 100 mg

73465-500MG 500 mg

73465-1G 1 g

73465-5G 5 g


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(RP,R′P)-1,1′-Bis(dicyclohexylphosphino)-2,2′-bis[(S)-α-(dimethylamino)benzyl]ferrocene, ≥97.0% (CHN)

(1S,1′S)-1,1′-Bis(dicyclohexylphosphino)-2,2′-bis[(S)-(dimethylamino)phenylmethyl]ferrocene(acc to CAS); Mandyphos SL-M002-2[849924‑78‑3]C52H74FeN2P2FW 844.95

Fe

N

H3C CH3

P

H

NCH3

CH3

P

H

73466-100MG 100 mg

73466-500MG 500 mg

73466-1G 1 g

73466-5G 5 g

(SP,S′P)-1,1′-Bis{bis[3,5‑bis(trifluoromethyl)phenyl]phos-phino}-2,2′-bis[(R)-α-(dimethylamino)benzyl]ferrocene,≥97.0% (19F-NMR)

Fe

N

CH3H3C

P

H

NH3C

H3CP

H

F3C

CF3CF3

CF3

F3C CF3

F3C

F3C

(1R,1′R)-1,1′-Bis[bis[3,5‑bis(trifluoromethyl)phenyl]phosphino]-2,2′-bis[(R)-(dimethylamino)phenylmethyl]ferrocene (acc to CAS); MandyphosSL-M003‑1[494227‑36‑0]C60H42F24FeN2P2FW 1364.74

73467-100MG 100 mg

73467-500MG 500 mg

73467-1G 1 g

73467-5G 5 g

(RP,R′P)-1,1′-Bis{bis[3,5‑bis(trifluoromethyl)phenyl]phos-phino}-2,2′-bis[(S)-α-(dimethylamino)benzyl]ferrocene,≥97.0% (19F-NMR)

Fe

N

H3C CH3

P

H

NCH3

CH3

P

H

CF3

F3CCF3

F3C

CF3F3C

CF3

CF3

(1S,1′S)-1,1′-Bis[bis[3,5‑bis(trifluoromethyl)phenyl]phosphino]-2,2′-bis[(S)-(dimethylamino)phenylmethyl]ferrocene (acc to CAS); MandyphosSL-M003‑2[849925‑10‑6]C60H42F24FeN2P2FW 1364.74

73468-100MG 100 mg

73468-500MG 500 mg

73468-1G 1 g

73468-5G 5 g

(SP,S′P)-1,1′-Bis[bis(4‑methoxy-3,5‑dimethylphenyl)phos-phino]-2,2′-bis[(R)-α-(dimethylamino)benzyl]ferrocene,≥97.0% (CHN)

Fe

N

CH3H3C

P

H

NH3C

H3CP

H

H3C

CH3CH3

CH3

H3C CH3

H3C

H3C

OCH3

H3CO

H3CO

OCH3

(1R,1′R)- 1,1′-Bis[bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]-2,2′-bis[(R)-(dimethylamino)phenylmethyl]ferrocene (acc to CAS); MandyphosSL-M004‑1[494227‑37‑1]C64H74FeN2O4P2FW 1053.08

73469-100MG 100 mg

73469-500MG 500 mg

73469-1G 1 g

73469-5G 5 g

(RP,R′P)-1,1′-Bis[bis(4‑methoxy-3,5‑dimethylphenyl)phos-phino]-2,2′-bis[(S)-α-(dimethylamino)benzyl]ferrocene,≥97.0% (CHN)

Fe

N

H3C CH3

P

H

NCH3

CH3

P

H

CH3

H3CCH3

H3C

CH3H3C

CH3

CH3

OCH3

OCH3

OCH3

H3CO

(1S,1′S)- 1,1′-Bis[bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]-2,2′-bis[(S)-(dimethylamino)phenylmethyl]ferrocene (acc to CAS); MandyphosSL-M004‑2[849925‑12‑8]C64H74FeN2O4P2FW 1053.08

73470-100MG 100 mg

73470-500MG 500 mg

73470-1G 1 g

73470-5G 5 g


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(SP,S′P)-1,1′-Bis[(R)-α-(dimethylamino)benzyl]-2,2′-bis[di(3,5‑xylyl)phosphino]ferrocene, ≥97.0% (CHN)

Fe

N

CH3H3C

P

H

NH3C

H3CP

H

H3C

CH3CH3

CH3

H3C CH3

H3C

H3C

(1R,1′R)-1,1′-Bis[bis(3,5‑dimethylphenyl)phosphino]-2,2′-bis[(R)-(dimethylamino)phenylmethyl]ferrocene (acc to CAS); Mandyphos SL-M009‑1[793718‑16‑8]C60H66FeN2P2FW 932.97

73471-100MG 100 mg

73471-500MG 500 mg

73471-1G 1 g

73471-5G 5 g

(RP,R′P)-1,1′-Bis[(S)-α-(dimethylamino)benzyl]-2,2′-bis[di(3,5‑xylyl)phosphino]ferrocene, ≥97.0% (CHN)

Fe

N

H3C CH3

P

H

NCH3

CH3

P

H

CH3

H3CH3C

H3C

CH3H3C

CH3

CH3

(1S,1′S)- 1,1′-Bis[bis(3,5‑dimethylphenyl)phosphino]-2,2′-bis[(S)-(dimethylamino)phenylmethyl]ferrocene (acc to CAS); Mandyphos SL-M009‑2[847997‑73‑3]C60H66FeN2P2FW 932.97

73472-100MG 100 mg

73472-500MG 500 mg

73472-1G 1 g

73472-5G 5 g

(SP,S′P)-1,1′-Bis[bis(2‑methylphenyl)phosphino]-2,2′-bis[(R)-α-(dimethylamino)benzyl]ferrocene, ≥97.0% (CHN)

(1R,1′R)-1,1′-Bis[bis(2-methylphenyl)phosphino]-2,2′-bis[(R)-(dimethylamino)phenylmethyl]ferrocene (acc to CAS);Mandyphos SL-M012-1[831226‑37‑0]C56H58FeN2P2FW 876.87

Fe

N

CH3H3C

P

H

NH3C

H3CP

H

CH3

CH3

H3C CH3

73473-100MG 100 mg

73473-500MG 500 mg

73473-1G 1 g

73473-5G 5 g

(RP,R′P)-1,1′-Bis[bis(2‑methylphenyl)phosphino]-2,2′-bis[(S)-α-(dimethylamino)benzyl]ferrocene, ≥97.0% (CHN)

(1S,1′S)-1,1′-Bis[bis(2-methylphenyl)phosphino]-2,2′-bis[(S)-(dimethylamino)phenylmethyl]ferrocene (acc to CAS);Mandyphos SL-M012-2[831226‑39‑2]C56H58FeN2P2FW 876.87

Fe

N

H3C CH3

P

H

NCH3

CH3

P

H

H3CH3C

CH3H3C

73474-100MG 100 mg

73474-500MG 500 mg

73474-1G 1 g

73474-5G 5 g


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Naud CatalystComplexes prepared in situ from RuCl2(PPh3)3 and chiralphosphine-oxazoline ligands (Naud catalysts) are effective catalysts forthe hydrogenation of various aryl ketones with up to 99% ee's andsubstrate to catalyst ratios of 10,000–50,000. The reaction tolerates highsubstrate concentrations,1 and several derivatives are being produced ona multikilogram scale. A pilot process has been developed for thehydrogenation of 3,5‑bistrifluoromethyl acetophenone.2 The reactionwas carried out twice on a 140 kg scale at 20 bar and 25 °C withsubstrate to catalyst ratios of 20,000 with an enantiomeric excess of>95%. After crystallization, (R)-3,5‑bistrifluoromethyl phenyl ethanol wasobtained with an ee between 97.7 and 98.6% in 70% chemical yield(Figure 1). A feasibility study was reported by Merck for the reduction ofa highly functionalized aryl ketone.3

References: (1) Naud, F. et al. Adv. Synth. Catal. 2006, 348, 47‑50. (2) Naud, F. et al.Org. Process Res. Dev. 2007, 11, 319. (3) Tellers, D. M. et al. Tetrahedron: Asymmetry 2006,17, 550.

N003-191991

PFe

O

N

• RuCl2CH3

H3C

• PPh3 N003-291992

PFe

O

N

• RuCl2H3C

CH3

• PPh3

R''

O

R'

R''

OH

R'

O

CF3

F3CF O

O

NHCbz

+ H2

RuCl2(PPh3)3 + N003

toluene / H2O / NaOH20-80 bar, r.t. 90 - 99% ee

up to 40,000 TON

RuCl2(PPh3)3 / N003-125°C, 20 bar95% ee; TON 20,000;TOF 2000 h-1

pilot process, Solvias/Rohner [2]

RuCl2(PPh3)3 / N003-240°C, 20 bar93% ee; TON 130; TOF ~8 h-1

Feasibility study, Merck [3]

Figure 1

(R)-2-[(RP)-2-(Diphenylphosphino)ferrocenyl]-4‑isopropyl-2‑oxazoline triphenylphosphine ruthenium(II) chlorideComplex

PFe

O

N

• RuCl2

PPh

Ph Ph

CH3

H3C

•

(1S)-1-(Diphenylphosphino)-2-[(R)-4‑isopropyl-2‑oxazolin-2‑yl]ferroceneTriphenylphosphine Ruthenium(II) chloride Complex (acc to CAS); NaudCatalyst SK-N003‑1z[849921‑25‑1]C46H43Cl2FeNOP2RuFW 915.61≥97.0% (CHN)

91991-100MG 100 mg

91991-500MG 500 mg

91991-1G 1 g

91991-5G 5 g

(S)-2-[(SP)-2-(Diphenylphosphino)ferrocenyl]-4‑isopropyl-2‑oxazoline triphenylphosphine ruthenium(II) dichlorideComplex, ≥97.0% (CHN)

(1R)-1-(Diphenylphosphino)-2-[(S)-4-isopropyl-2-oxazolin-2-yl]ferrocene TriphenylphosphineRuthenium(II) chloride Complex (acc to CAS);Naud Catalyst SK-N003-2z[212133‑11‑4]C46H43Cl2FeNOP2RuFW 915.61

PFe

O

N

• RuCl2

PPh

PhPh

H3C

CH3

•

91992-100MG 100 mg

91992-500MG 500 mg

91992-1G 1 g

91992-5G 5 g

ButiphaneIn many respects the catalytic profile of the Butiphane ligands1 P005‑1(53361) and P005‑2 (53362) is rather similar to that of otherphospholane diphosphines such as DuPhos and its many analogs.2 Up tonow, the potential of the ligand has only been demonstrated in the Rhcatalyzed hydrogenation of dehydroamino acid derivatives, enamides,and itaconates, achieving ee values of up to 98.7%.1

References: (1) Berens, U. et al. Eur. J. Org. Chem. 2006, 2100. (2) Cobley, C. J.; Moran, P.H. In Handbook of Homogeneous Hydrogenation; de Vries, J. G.; Elsevier C. J., Eds.; Wiley-VCH, 2007; p 773.

(R,R,R,R)-2,3‑Bis(2,5‑dimethyl-phospholanyl)benzo[b]thio-phene cyclooctadiene rhodium(I) tetrafluoroborate Com-plex, ≥97.0% (19F-NMR)

Methyl-Butiphane SK-P005-1a[511543‑00‑3]C28H40BF4P2RhSFW 660.34

P

P

Rh+

CH3

H3C CH3

H3C

S

BF4-

53361-100MG 100 mg

53361-500MG 500 mg

53361-1G 1 g

53361-5G 5 g

(S,S,S,S)-2,3‑Bis(2,5‑dimethyl-phospholanyl)benzo[b]thio-phene cyclooctadiene rhodium(I) tetrafluoroborate Com-plex, ≥97.0% (19F-NMR)

Methyl-Butiphane SK-P005-2a[849920‑73‑6]C28H40BF4P2RhSFW 660.34

P

P

Rh+

CH3

H3C CH3

H3C

S

BF4-

53362-100MG 100 mg

53362-500MG 500 mg

53362-1G 1 g

53362-5G 5 g


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Kit

Solvias® Chiral Ligands Kit

Chiral Phosphine Ligands, Kit from Solvias®

≥97% (each component)

Components(R)-2-[(RP)-2-(Diphenylphosphino)ferrocenyl]-4‑isopropyl-2‑oxazoline triphenylphosphineruthenium(II) chloride Complex (Aldrich 91991)(S)-2-[(SP)-2-(Diphenylphosphino)ferrocenyl]-4‑isopropyl-2‑oxazoline triphenylphosphineruthenium(II) dichloride Complex (Aldrich 91992)(R,R,R,R)-2,3‑Bis(2,5‑dimethyl-phospholanyl)benzo[b]thiophene cyclooctadiene rhodium(I)tetrafluoroborate Complex (Aldrich 53361)(S,S,S,S)-2,3‑Bis(2,5‑dimethyl-phospholanyl)benzo[b]thiophene cyclooctadiene rhodium(I)tetrafluoroborate Complex (Aldrich 53362)(R)-1-[(SP)-2-(Diphenylphosphino)ferrocenyl]ethyldicyclohexylphosphine (Aldrich 88717)(S)-1-[(RP)-2-(Diphenylphosphino)ferrocenyl]ethyldicyclohexylphosphine (Aldrich 88718)(R)-1-[(SP)-2-(Diphenylphosphino)ferrocenyl]ethyldi-tert-butylphosphine (Aldrich 88719)(S)-1-[(RP)-2-(Diphenylphosphino)ferrocenyl]ethyldi-tert-butylphosphine (Aldrich 88720)(R)-1-[(SP)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldicyclohexylphosphine (Aldrich 88721)(S)-1-[(RP)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldicyclohexylphosphine (Aldrich 88722)(R)-1-[(SP)-2-(Dicyclohexylphosphino)ferrocenylethyl]diphenylphosphine (Aldrich 88723)(S)-1-[(RP)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldiphenylphosphine (Aldrich 88724)(R)-1-[(SP)-2-(Diphenylphosphino)ferrocenyl]ethyldi(3,5‑xylyl)phosphine (Aldrich 88725)(S)-1-[(RP)-2-(Diphenylphosphino)ferrocenyl]ethyldi(3,5‑xylyl)phosphine (Aldrich 88726)(R)-1-{(SP)-2-[Bis[3,5‑bis(trifluoromethyl)phenyl]phosphino]ferrocenyl}ethyldicyclohexylphos-phine (Aldrich 88727)(S)-1-{(RP)-2-[Bis[3,5‑bis(trifluoromethyl)phenyl]phosphino]-ferrocenyl}ethyldicyclohexyl-phosphine (Aldrich 88728)(R)-1-{(SP)-2-[Bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]ferrocenyl}ethyldicyclohexyl-phosphine (Aldrich 88729)(S)-1-{(RP)-2-[Bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]ferrocenyl}ethyldicyclohexyl-phosphine (Aldrich 88730)(R)-1-{(SP)-2-[Bis[3,5‑bis(trifluoromethyl)phenyl]phosphino]ferrocenyl}ethyldi(3,5‑xylyl)phos-phine (Aldrich 88731)(S)-1-{(RP)-2-[Bis[3,5‑bis(trifluoromethyl)phenyl]phosphino]ferrocenyl}ethyldi(3,5‑xylyl)phos-phine (Aldrich 88732)(R)-1-[(SP)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldi-tert-butylphosphine (Aldrich 88733)(S)-1-[(RP)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldi-tert-butylphosphine (Aldrich 88734)(R)-1-{(SP)-2-[Bis[4-(trifluoromethyl)phenyl]phosphino]ferrocenyl}ethyldi-tert-butylphosphine(Aldrich 88735)(S)-1-{(RP)-2-[Bis[4-(trifluoromethyl)phenyl]phosphino]ferrocenyl}ethyldi-tert-butylphosphine(Aldrich 88736)(R)-1-[(SP)-2-[Bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]ferrocenyl}ethyldi-tert-butyl-phosphine (Aldrich 88737)(S)-1-[(RP)-2-[Bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]ferrocenyl}ethyldi-tert-butyl-phosphine (Aldrich 88738)(R)-1-{(SP)-2-[Di(2‑furyl)phosphino]ferrocenyl}ethyldi(3,5‑xylyl)phosphine (Aldrich 88739)(S)-1-{(RP)-2-[Di(2‑furyl)phosphino]ferrocenyl}ethyldi(3,5‑xylyl)phosphine (Aldrich 88740)(R)-1-{(SP)-2-[Di(2‑furyl)phosphino]ferrocenyl}ethyldi-tert-butylphosphine (Aldrich 88741)(S)-1-{(RP)-2-[Di(2‑furyl)phosphino]ferrocenyl}ethyldi-tert-butylphosphine (Aldrich 88742)(R)-1-{(SP)-2-[Di(1‑naphthyl)phosphino]ferrocenyl}ethyldi-tert-butylphosphine (Aldrich88743)(S)-1-{(RP)-2-[Di(1‑naphthyl)phosphino]ferrocenyl}ethyldi-tert-butylphosphine (Aldrich88744)(R)-1-{(SP)-2-[Di(1‑naphthyl)phosphino]ferrocenyl}ethyldi(3,5‑xylyl)phosphine (Aldrich88745)(S)-1-{(RP)-2-[Di(1‑naphthyl)phosphino]ferrocenyl}ethyldi(3,5‑xylyl)phosphine (Aldrich88746)(R)-1-{(SP)-2-[Bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]ferrocenyl}-ethyldi(3,5‑xylyl)phosphine (Aldrich 88747)(S)-1-{(RP)-2-[Bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]ferrocenyl}-ethyldi(3,5‑xylyl)phosphine (Aldrich 88748)(R)-1-{(SP)-2-[Bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]ferrocenyl}-ethylbis(2‑methyl-phenyl)phosphine (Aldrich 88749)(S)-1-{(RP)-2-[Bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]ferrocenyl}-ethylbis(2‑methyl-

phenyl)phosphine (Aldrich 88750)(R)-1-{(SP)-2-[Di(2‑furyl)phosphino]ferrocenyl}ethylbis(2‑methylphenyl)phosphine (Aldrich88751)(S)-1-{(RP)-2-[Di(2‑furyl)phosphino]ferrocenyl}ethylbis(2‑methylphenyl)phosphine (Aldrich88752)(R)-1-[(SP)-2-(Di-tert-butylphosphino)ferrocenyl]ethyldiphenylphosphine (Aldrich 88753)(S)-1-[(RP)-2-(Di-tert-butylphosphino)ferrocenyl]ethyldiphenylphosphine (Aldrich 88754)(R)-1-[(SP)-2-(Di-tert-butylphosphino)ferrocenyl]ethylbis(2‑methylphenyl)phosphine (Aldrich88755)(S)-1-[(RP)-2-(Di-tert-butylphosphino)ferrocenyl]ethylbis(2‑methylphenyl)phosphine (Aldrich88756)(SP,S′P)-1,1′-Bis[(R)-α-(dimethylamino)benzyl]-2,2′-bis(diphenylphosphino)ferrocene (Aldrich73463)(RP,R′P)-1,1′-Bis[(S)-α-(dimethylamino)benzyl]-2,2′-bis(diphenylphosphino)ferrocene (Aldrich73464)(SP,S′P)-1,1′-Bis(dicyclohexylphosphino)-2,2′-bis[(R)-α-(dimethylamino)benzyl]ferrocene (Al-drich 73465)(RP,R′P)-1,1′-Bis(dicyclohexylphosphino)-2,2′-bis[(S)-α-(dimethylamino)benzyl]ferrocene (Al-drich 73466)(SP,S′P)-1,1′-Bis{bis[3,5‑bis(trifluoromethyl)phenyl]phosphino}-2,2′-bis[(R)-α-(dimethylamino)benzyl]ferrocene (Aldrich 73467)(RP,R′P)-1,1′-Bis{bis[3,5‑bis(trifluoromethyl)phenyl]phosphino}-2,2′-bis[(S)-α-(dimethylamino)benzyl]ferrocene (Aldrich 73468)(SP,S′P)-1,1′-Bis[bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]-2,2′-bis[(R)-α-(dimethylami-no)benzyl]ferrocene (Aldrich 73469)(RP,R′P)-1,1′-Bis[bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]-2,2′-bis[(S)-α-(dimethylami-no)benzyl]ferrocene (Aldrich 73470)(SP,S′P)-1,1′-Bis[(R)-α-(dimethylamino)benzyl]-2,2′-bis[di(3,5‑xylyl)phosphino]ferrocene (Al-drich 73471)(RP,R′P)-1,1′-Bis[(S)-α-(dimethylamino)benzyl]-2,2′-bis[di(3,5‑xylyl)phosphino]ferrocene (Al-drich 73472)(SP,S′P)-1,1′-Bis[bis(2‑methylphenyl)phosphino]-2,2′-bis[(R)-α-(dimethylamino)benzyl]ferro-cene (Aldrich 73473)(RP,R′P)-1,1′-Bis[bis(2‑methylphenyl)phosphino]-2,2′-bis[(S)-α-(dimethylamino)benzyl]ferro-cene (Aldrich 73474)(RP)-1-[(R)-α-(Dimethylamino)-2-(diphenylphosphino)benzyl]-2‑diphenylphosphinoferrocene(Aldrich 73475)(SP)-1-[(S)-α-(Dimethylamino)-2-(diphenylphosphino)benzyl]-2‑diphenylphosphinoferrocene(Aldrich 73476)(RP)-1‑Dicyclohexylphosphino-2-[(R)-α-(dimethylamino)-2-(dicyclohexylphosphino)benzyl]ferrocene (Aldrich 07541)(SP)-1‑Dicyclohexylphosphino-2-[(S)-α-(dimethylamino)-2-(dicyclohexylphosphino)benzyl]ferrocene (Aldrich 07542)(R)-1-{(RP)-2-[2-(Diphenylphosphino)phenyl]ferrocenyl}ethylbis[3,5‑bis-(trifluoromethyl)phe-nyl]phosphine (Aldrich 65671)(S)-1-{(SP)-2-[2-(Diphenylphosphino)phenyl]ferrocenyl}ethylbis[3,5‑bis-(trifluoromethyl)phe-nyl]phosphine (Aldrich 65672)(R)-1-{(RP)-2-[2-(Diphenylphosphino)phenyl]ferrocenyl}ethyldiphenylphosphine (Aldrich65673)(S)-1-{(SP)-2-[2-(Diphenylphosphino)phenyl]ferrocenyl}ethyldiphenylphosphine (Aldrich65674)(R)-1-{(RP)-2-[2-(Diphenylphosphino)phenyl]ferrocenyl}ethyldicyclohexylphosphine (Aldrich65675)(S)-1-{(SP)-2-[2-(Diphenylphosphino)phenyl]ferrocenyl}ethyldicyclohexylphosphine (Aldrich65676)(R)-1-{(RP)-2-[2-[Bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]phenyl]ferrocenyl}ethylbis[3,5‑bis(trifluoromethyl)phenyl]phosphine (Aldrich 65677)(S)-1-{(SP)-2-[2-[Bis(4‑methoxy-3,5‑dimethylphenyl)phosphino]phenyl]ferrocenyl}ethylbis[3,5‑bis(trifluoromethyl)phenyl]phosphine (Aldrich 65678)(R)-1-{(RP)-2-[2-(Diphenylphosphino)phenyl]ferrocenyl}ethyldi(3,5‑xylyl)phosphine (Aldrich65679)(S)-1-{(SP)-2-[2-(Diphenylphosphino)phenyl]ferrocenyl}ethyldi(3,5‑xylyl)phosphine (Aldrich65680)(R)-1-{(RP)-2-[2-(Dicyclohexylphosphino)phenyl]ferrocenyl}ethylbis[3,5‑bis(trifluoromethyl)phenyl]phosphine (Aldrich 65681)(S)-1-{(SP)-2-[2-(Dicyclohexylphosphino)phenyl]ferrocenyl}ethylbis[3,5‑bis(trifluoromethyl)phenyl]phosphine (Aldrich 65682)(R)-1-{(RP)-2-[2-[Di(3,5‑xylyl)phosphino]phenyl]ferrocenyl}ethyldi(3,5‑xylyl)phosphine (Al-drich 65683)(S)-1-{(SP)-2-[2-[Di(3,5‑xylyl)phosphino]phenyl]ferrocenyl}ethyldi(3,5‑xylyl)phosphine (Al-drich 65684)(R)-1-{(RP)-2-[2-(Diphenylphosphino)phenyl]ferrocenyl}ethyldi(2‑norbornyl)phosphine (Al-drich 65685)(S)-1-{(SP)-2-[2-(Diphenylphosphino)phenyl]ferrocenyl}ethyldi(2‑norbornyl)phosphine (Al-drich 65686)(S)-(-)-(6,6′-Dimethoxybiphenyl-2,2′-diyl)bis(diphenylphosphine) (Aldrich 29511)(R)-(+)-(6,6′-Dimethoxybiphenyl-2,2′-diyl)bis(diphenylphosphine) (Aldrich 29510)(R)-(6,6′-Dimethoxybiphenyl-2,2′-diyl)bis[bis(3,5‑di-tert-butyl-4‑methoxyphenyl)phosphine](Aldrich 29512)(S)-(6,6′-Dimethoxybiphenyl-2,2′-diyl)bis[bis(3,5‑di-tert-butyl-4‑methoxyphenyl)phosphine](Aldrich 29513)

12000-1KT 1 kit


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UMICORE Precatalysts for Asymmetric ReactionsSigma-Aldrich® and Umicore have partnered to offer a portfolio of metal precatalysts for rapid screening of asymmetric and cross-coupling reactions. This partnership ensures the reproducibility of milligram-to-ton-scale reactions.

RhCl

Cl

ClRh

Cl

RuCl Cl

ClRu

Cl

Pd2dba3

683094 683108

683140

683183 686891

683213 683221 683191

683124 683345

693774 683086

683116 683132 683175

683167

683205

683353

683388 683396

IrBARF Ir

OH3C

OH3C

IrCl

ClIr

RhO

H3C

OH3C

RhO

H3C

OH3C

RhCl

ClRh Rh

BF4 • x H2O RhBF4

Rh

Cl

ClRh

RhO

H3C

OH3C

CO

CO Ru

H3C

H3C

RuCl

Cl

n

PdO

H3C

OH3C

OCH3

OCH3

IRu

I

IRu

I

PdCl

PdCl

ClRu

Cl

ClRu

Cl

Pd(OAc)2

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DuPhos and BPE Phospholane Ligands and Complexes

In the early 1990s, Burk and coworkers developed new electron-rich C2

symmetric bis(phospholane) ligands. The modular nature of these ligandsallowed for variation of both phosphane substituent and backbonestructures, leading to an extensive library of ligands for enantioselectivecatalytic reactions. The large-scale capacity of these robust catalysts isobserved in the efficiency (substrate-to-catalyst (s/c) ratios up to 50,000)and the high activities (TOF >5,000 h-1) in a myriad of enamide andketone reductions. Under optimized conditions, (R,R)-Me-BPE-Rhreduced N-acetyl α-arylenamides in >95% ee to yield valuableα-1‑arylethylamines (Scheme 1).1

It should be noted that Me-DuPhos-Rh complexes were equallyeffective in asymmetric reductions of prochiral enamides. The generalutility of these phospholane ligands is illustrated in the incrediblediversity-oriented production of a vast array of amino acid derivatives(Scheme 2).2

Asymmetric Hydrogenation of the C=N GroupBurk and co-workers exploited the high activity of the Ethyl-DuPhosligand via a powerful catalytic reductive amination process.3 Theprocedure exhibits general applicability in the reduction of a wide varietyof N-aroylhydrazones, yielding enantioselectivies for most substrates>90% (Scheme 3). Additionally this (Et-DuPhos)-Rh catalyst systemdisplays exceptionally high chemoselectivies, yielding little or noreduction of unfunctionalized alkenes, alkynes, ketones, aldehydes, andimines in competition experiments. The synthetic utility of theseasymmetric hydrazone reductions is enhanced by their facile reaction atambient temperature with samarium diiodide, which proceed with noobservable loss of optical purity.

Catalytic Hydrogenation of EnamidesBurk has also pioneered the asymmetric hydrogenation of variousenamido olefins affording highly enantiopure unsaturated amino acidproducts.4 The ((S,S)-Et-DuPhos)-Rh) catalyst system controls thereactivity of conjugated substrates with high regioselectivies as well.Under the standard hydrogenation conditions (s/c =500, H2 pressuresranging from 60 to 90 psi, and 0.5−3 h), this catalyst gave less than2% overreduction, with all products isolated in better than 95% yield.The authors elaborated upon this outstanding catalyst reactivity bydemonstrating a concise and highly selective synthesis of the naturalproduct (−)-bulgecinine, preceeded by formation of the key chiralintermediate in 99% yield with 99.3% ee (Scheme 4).

Preparation of Chiral Organicswith C–O Stereogenic CentersNeil Boaz has also utilized rhodium(I)-((R,R)-Me-DuPhos) catalyst 1 toproduce chiral alcohols via the asymmetric hydrogenation of enol esters(Scheme 5). Allylic alcohol derivatives are desirable organic buildingblocks in diversity-oriented synthesis, because the olefin can be furtherfunctionalized after the stereochemistry has been set in thehydrogenation.5 Under asymmetric hydrogenation conditions, theinitially formed propargylic acetate was subsequently reduced to yield theZ-allylic acetate. Impressively, the enantioselectivity observed in thisreaction was very high among the general substrate class 2a-c.

Burk and co-workers have also designed highly effective catalysts for theasymmetric reduction of C=O bonds under hydrogenation conditions.6 Inthis case, the methodology proceeded via use of a chiral Ru(II)Br2-(i-Pr-BPE) complex, which was prepared by reacting [(COD)Ru(2‑methylallyl)2]with the BPE ligand followed by treatment with methanolic HBr. A varietyof ketoesters were rapidly hydrogenated as mediated by this catalyst tothe hydroxyl esters with very high enantioselectivities >98% ee for thealkyl-substituted substrates (Scheme 6).

[((R,R)-Me-BPE)-Rh]+

Ph N(H)Ac

H

MeOH, 60 psi H2, rt, 12 h

(S/C = 500)

Ph N(H)Ac

H

95.2% ee

Scheme 1

R1

R2N(H)COR3

CO2R4

CO2Me

N(H)Ac

CO2Me

O N(H)Boc CO2MeN

N(H)CBz

CO2Me

O

AcO OAc

OAcAcOCO2Me

N(H)Boc

NOMe

O

C7F15CO2Me

N(H)CBzCO2Me

N(H)CBz

F

CO2Me

N(H)Boc

Scheme 2

Ph

N

MeH2 (4 atm), 2-propanol, 2 h, rt

92% ee

P PRh

OTf

N

O

p-Me2NC6H4

H

0.2 mol %

Ph

HN

Me

N

O

p-Me2NC6H4

H

Scheme 3

H2 (4 atm), MeOH, 2 h, rt

99%, 99.3% ee

P PRh

OTf

S/C = 500:1OTBS CO2Me

NHAc

OTBSCO2Me

NHAc

H

Scheme 4

H2 (30 psi), MeOH, rt

2a: R = n-C5H11, 98.5% ee2b: R = Ph, 97.8% ee2c: R = CH2CH2OCH2Ph, > 98% ee

Rh-(Me-DuPhos) cat. 1

R

OAc

R

OAc

MeH

R OAc

MeH

Scheme 5

H2 (60 psi), MeOH/H2O, 18 h

P PRu

0.4 mol %

Br Br

O

CO2MeOH

CO2Me

99% ee

Scheme 6


DuPhosandBPE


Enantioselective Hydrogenationof Alkenes and IminesThe use of gold complexes to effect catalytic transformations is on therise, with numerous reports of catalytically active gold species.7 Sanchezand co-workers have now reported the first example of a goldhydrogenation catalyst utilized in asymmetric transformations.8 Theauthors found that the bulkiest substrate, which incorporates a diethyl2‑naphthylidenesuccinate group, proceeds under the reaction conditionsto afford the highest enantioselectivities due to reactant control(Scheme 7). Future plans in gold-mediated asymmetric hydrogenationinvolve substantial modifications to the ligand structure to provide higherlevels of enantiocontrol in this reaction paradigm.

Enantioselective Allylboration of KetonesThe Shibasaki research group has also championed the use of theDuPhos ligand system for asymmetric catalysis.9 They have now reportedthe first general catalytic, enantioselective allylation reaction withketones, which employs copper salts and a rare-earth lanthanideadditive. Impressively, a diverse array of aromatic, heteroaromatic,α,β-unsaturated, and aliphatic ketones are rapidly allylated at ambienttemperature and under low catalyst loadings (Scheme 8). Theenantioselectivities range from 67 to 92%; however, the reactionappears to be quite general for both the allylation and crotylborationreaction paradigms.

Enantioselective Addition of Dialkylzincto β-NitroalkenesThe use of chiral bis(phosphine) monoxide ligand has found widespreadapplications in catalysis. Côté et al. reported the use of Me-DuPhosmonoxide in the addition of dialkyzinc to nitroalkenes. Various chiralnitroalkanes were synthesized with excellent yields and selectivities(Scheme 9).10

References: (1) Burk, M. J. et al. J. Am. Chem. Soc. 1996, 118, 5142. (2)(a) Burk, M. J. Acc.Chem. Res. 2000, 33, 363. (b) Burk, M. J. et al. J. Org. Chem. 2003, 68, 5731. (3) Burk, M.J. et al. J. Am. Chem. Soc. 1992, 114, 6266. (4) Burk, M. J. et al. J. Am. Chem. Soc. 1998,120, 657. (5) Burk, M. J. et al. J. Am. Chem. Soc. 1995, 117, 4423. (6) Burk, M. J. et al. J.Org. Chem. 1999, 64, 3290. (7) Dyker, G. Angew. Chem., Int. Ed. 2000, 39, 4237.(8) Sanchez, F. et al. Chem. Commun. 2005, 3451. (9) Shibasaki, M. et al. J. Am. Chem. Soc.2004, 126, 8910. (10) Côté, A. et al. Org. Lett. 2007, 9, 85.

H2 (4 atm), EtOH, rt

P

P

S/C = 1000:1

95% ee

Au

Au

ClCl

EtO2C

EtO2C H

R EtO2C

EtO2C H

R

Scheme 7

La(OiPr)3 (4.5 mol %)DMF, 1 h, 40 C

CuF2 H2O (3 mol %)(R,R)-iPr-DuPhos (6 mol %)

o

O

+ BO

O

(1.2 equiv)

OH

99%, 91% ee

Scheme 8

R

NO2

R

NO2

P

P

Me

Me

Me

Me

O

CuOTf, Et2ZnEt2O, -70 °C, 16h

NO2 NO2

Cl

NO2

OMe

92% 97.5:2.5

93%93:1

98%97.5:2.5

Scheme 9

(−)-1,2‑Bis[(2R,5R)-2,5‑dimethylphospholano]benzene

(2R,2'R,5R,5'R)-2,2',5,5'-Tetramethyl-1,1'-(o-phenylene)diphospholane; (R,R)-Methyl-DUPHOS; (R,R)-Me-DUPHOS[147253‑67‑6]C18H28P2FW 306.36 P

P

CH3

CH3

H3C

H3C

S: 22-24/25

665258-100MG 100 mg

665258-500MG 500 mg

665258-2G 2 g

(+)-1,2‑Bis[(2S,5S)-2,5‑dimethylphospholano]benzene

(2S,2'S,5S,5'S)-2,2',5,5'-Tetramethyl-1,1'-(o-phenylene)diphospholane; (S,S)-Methyl-DUPHOS; (S,S)-Me-DUPHOS[136735‑95‑0]C18H28P2FW 306.36 P

P

CH3

CH3

H3C

H3C

665266-100MG 100 mg

665266-500MG 500 mg

665266-2G 2 g

(−)-1,2‑Bis[(2R,5R)-2,5‑diethylphospholano]benzene

(2R,2'R,5R,5'R)-2,2'-5,5'-Tetraethyl-1,1'-(o-phenylene)diphospholane; (R,R)-Ethyl-DUPHOS[136705‑64‑1]C22H36P2FW 362.47 P

P

H3C

CH3H3C

CH3

Fp: 110 °C (230 °F)

668494-100MG 100 mg

668494-500MG 500 mg

668494-2G 2 g

(+)-1,2‑Bis[(2S,5S)-2,5‑diethylphospholano]benzene

(2S,2'S,5S,5'S)-2,2',5,5'-Tetraethyl-1,1'-(o-phenylene)diphospholane; (S,S)-Ethyl-DUPHOS[136779‑28‑7]C22H36P2FW 362.47 P

P

H3C

CH3H3C

CH3

Fp: 110 °C (230 °F)

668486-100MG 100 mg

668486-500MG 500 mg

668486-2G 2 g


DuPhosand

BPE














(+)-1,2‑Bis[(2R,5R)-2,5‑diisopropylphospholano]benzene

(R,R)-i-Pr-DUPHOS[136705‑65‑2]C26H44P2FW 418.58

P

P

H3C

H3CCH3

H3C

H3C

CH3

CH3

H3C

Fp: 230 °F

668524-100MG 100 mg

668524-500MG 500 mg

668524-2G 2 g

(−)-1,2‑Bis((2S,5S)-2,5‑diisopropylphospholano)benzene

(S,S)-i-Pr-DUPHOS[147253‑69‑8]C26H44P2FW 418.58

P

P

CH3

H3C

H3C

H3C

CH3

CH3

CH3

CH3

668176-100MG 100 mg

668176-500MG 500 mg

668176-2G 2 g

1,2-Bis[(2R,5R)-2,5-dimethylphospholano]benzenemonooxide

8

R,R-Me-BozPhos; (2R,5R)-1-{2-[(2R,5R)-2,5-Dimethylphos-pholan-1-yl]phenyl}-2,5-dimethylphospholane 1-oxide[638132‑66‑8]C18H28OP2FW 322.36 P

P

CH3

CH3

H3C

H3C

O

678635-100MG 100 mg

678635-500MG 500 mg

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1,2-Bis[(2S,5S)-2,5-dimethylphospholano]benzenemonooxide

8

S,S-Me-BozPhos; (2S,5S)-1-{2-[(2S,5S)-2,5-Dimethylphos-pholan-1-yl]phenyl}-2,5-dimethylphospholane 1-oxideC18H28OP2FW 322.36

P

P

CH3

CH3

H3C

H3C

O

678562-100MG 100 mg

678562-500MG 500 mg

1,2-Bis[(2R,5R)-2,5-diethylphospholano]benzene(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate

8

(R,R)-Et-DUPHOS-Rh[228121‑39‑9]C30H48BF4P2RhFW 660.36

RhP

PBF4

H3C CH3

CH3H3C

698377-50MG 50 mg

698377-250MG 250 mg

1,2-Bis[(2S,5S)-2,5-diethylphospholano]benzene(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate

8

(S,S)-Et-DUPHOS-Rh[213343‑64‑7]C30H48BF4P2RhFW 660.36

RhP

P

H3C CH3

CH3H3C

BF4-

698385-50MG 50 mg

698385-250MG 250 mg

1,2-Bis[(2R,5R)-2,5-diethylphospholano]benzene(1,5-cyclooctadiene)rhodium(I) trifluoromethanesulfonate

8

(R,R)-Et-DUPHOS-Rh[136705‑77‑6]C31H48F3O3P2RhSFW 722.62

RhP

P

H3C CH3

CH3H3C

CF3SO3-

LR: 36/37/38 S: 26-36/37

698393-50MG 50 mg

698393-250MG 250 mg

1,2-Bis[(2S,5S)-2,5-diethylphospholano]benzene(1,5-cyclooctadiene)rhodium(I) trifluoromethanesulfonate

8

(S,S)-Et-DUPHOS-Rh[142184‑30‑3]C31H48F3O3P2RhSFW 722.62

RhP

P

H3C CH3

CH3H3C

CF3SO3-

LR: 36/37/38 S: 26

698407-50MG 50 mg

698407-250MG 250 mg


DuPhosandBPE



















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1,2-Bis[(2R,5R)-2,5-diisopropylphospholano]benzene(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate

8

[569650‑64‑2]C24H56BF4P2RhFW 596.36

RhP

PBF4

H3C CH3

CH3H3C

H3C

H3C

CH3

CH3

698342-50MG 50 mg

698342-250MG 250 mg

1,2-Bis[(2S,5S)-2,5-diisopropylphospholano]benzene(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate

8

C34H56BF4P2RhFW 716.47

RhP

PBF4

H3C CH3

CH3H3C

H3C

H3C

CH3

CH3

698334-50MG 50 mg

698334-250MG 250 mg

1,2‑Bis[(2R,5R)-2,5‑dimethylphospholano]benzene(cycloocta-diene)rhodium(I) tetrafluoroborate

[210057‑23‑1]C26H40BF4P2RhFW 604.25 Rh

P

PH3C

CH3

CH3

H3C

BF4

675520-100MG 100 mg

675520-500MG 500 mg

1,2‑Bis[(2S,5S)-2,5‑dimethylphospholano]benzene(cycloocta-diene)rhodium(I) tetrafluoroborate

[205064‑10‑4]C26H40BF4P2RhFW 604.25 Rh

P

PH3C

CH3

CH3

H3C

BF4

675539-100MG 100 mg

675539-500MG 500 mg

1,2‑Bis[(2R,5R)-2,5‑dimethylphospholano]benzene(cycloocta-diene)rhodium(I) trifluoromethanesulfonate, ≥97%

RhP

PH3C

CH3

CH3

H3C

F3CS

O

O O

[187682‑63‑9]C27H40F3O3P2RhSFW 666.52

675571-100MG 100 mg

675571-500MG 500 mg

1,2‑Bis[(2S,5S)-2,5‑dimethylphospholano]benzene(cycloocta-diene)rhodium(I) trifluoromethanesulfonate, 97%

[136705‑75‑4]C27H40F3O3P2RhSFW 666.52 Rh

P

PCH3

H3C CH3

H3C

F3C S O

O

O

LR: 36/37/38 S: 26-36/37

675563-100MG 100 mg

675563-500MG 500 mg

(+)-1,2‑Bis((2R,5R)-2,5‑diethylphospholano)ethane

(R,R)-Et-BPE[136705‑62‑9]C18H36P2FW 314.43

P

P

CH3H3C

CH3H3C

Fp: 110 °C (230 °F)

668478-100MG 100 mg

668478-500MG 500 mg

668478-2G 2 g

(−)-1,2‑Bis((2S,5S)-2,5‑diethylphospholano)ethane

(S,S)-Et-BPE[136779‑27‑6]C18H36P2FW 314.43

P

P

CH3H3C

H3C CH3

JR: 17 S: 6

668451-100MG 100 mg

668451-500MG 500 mg

668451-2G 2 g

1,2‑Bis((2R,5R)-2,5‑diisopropylphospholano)ethane

C22H44P2FW 370.53

P

P

H3C

H3C

CH3

CH3

CH3

CH3

H3C

H3C

668443-100MG 100 mg

668443-500MG 500 mg

668443-2G 2 g

1,2‑Bis((2S,5S)-2,5‑diisopropylphospholano)ethane

C22H44P2FW 370.53

P

P

H3C

H3C

CH3

CH3

CH3

CH3

H3C

H3C

668435-100MG 100 mg

668435-500MG 500 mg

668435-2G 2 g


DuPhosand

BPE


























(+)-1,2‑Bis((2R,5R)-2,5‑dimethylphospholano)ethane

(R,R)-Me-BPE[129648‑07‑3]C14H28P2FW 258.32

P

P

CH3

H3C CH3

H3C

JR: 11-17

665231-100MG 100 mg

665231-500MG 500 mg

665231-2G 2 g

(−)-1,2‑Bis((2S,5S)-2,5‑dimethylphospholano)ethane

(S,S)-Me-BPE[136779‑26‑5]C14H28P2FW 258.32

P

P

CH3

H3C CH3

H3C

JR: 11-17

665207-100MG 100 mg

665207-500MG 500 mg

665207-2G 2 g

(−)-1,2‑Bis((2R,5R)-2,5‑diphenylphospholano)ethane

[528565‑79‑9]C34H36P2FW 506.60

P

P

667811-100MG 100 mg

667811-500MG 500 mg

667811-2G 2 g

(+)-1,2‑Bis((2S,5S)-2,5‑diphenylphospholano)ethane

[824395‑67‑7]C34H36P2FW 506.60

P

P

667854-100MG 100 mg

667854-500MG 500 mg

667854-2G 2 g

1,2‑Bis[(2R,5R)-2,5-(dimethylphospholano]ethane(cycloocta-diene)rhodium(I) tetrafluoroborate

[305818‑67‑1]C22H40BF4P2RhFW 556.21 Rh

P

PH3C

CH3

CH3

H3C

BF4

LR: 36/37/38 S: 26

675555-100MG 100 mg

675555-500MG 500 mg

1,2‑Bis[(2S,5S)-2,5‑dimethylphospholano]ethane(cycloocta-diene)rhodium(I) tetrafluoroborate

[213343‑65‑8]C22H40BF4P2RhFW 556.21 Rh

P

PH3C

CH3

CH3

H3C

BF4

LR: 36/37/38 S: 26

675547-100MG 100 mg

675547-500MG 500 mg

1,2-Bis[(2R,5R)-2,5-diphenylphospholano]ethane(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate

8

(R,R)-Ph-BPE-Rh[528565‑84‑6]C42H48BF4P2RhFW 804.49

RhP

PPh

Ph

Ph

Ph

BF4

LR: 36/37/38 S: 26-36/37

698350-50MG 50 mg

698350-250MG 250 mg

1,2-Bis[(2S,5S)-2,5-diphenylphospholano]ethane(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate

8

(S,S)-Ph-BPE-RhC42H48BF4P2RhFW 804.49 Rh

P

PPh

Ph

Ph

Ph

BF4

LR: 36/37/38 S: 26

698369-50MG 50 mg

698369-250MG 250 mg

1,1′-Bis((2R,5R)-2,5‑diethylphospholano)ferrocene

R,R-Et-Ferrocelane™C26H40FeP2FW 470.39

Fe

P

P

H3C

H3C

CH3

CH3

680990-100MG 100 mg

680990-500MG 500 mg

1,1′-Bis((2S,5S)-2,5‑diethylphospholano)ferrocene

S,S-Et-Ferrocelane™C26H40FeP2FW 470.39

Fe

P

P

H3C

H3C

CH3

CH3

681008-100MG 100 mg

681008-500MG 500 mg


DuPhosandBPE


























1,1′-Bis[(2R,5R)-2,5-diisopropylphospholano]ferrocene 8

C30H48FeP2FW 526.49

P

H3CCH3

H3CCH3

P

CH3H3C

CH3

H3C

Fe

684309-100MG 100 mg

684309-500MG 500 mg

1,1′-Bis[(2S,5S)-2,5-diisopropylphospholano]ferrocene 8

C30H48FeP2FW 526.49

P

H3CCH3

H3CCH3

P

CH3H3C

CH3

H3C

Fe

684406-100MG 100 mg

684406-500MG 500 mg

1,1′-Bis[(2R,5R)-2,5‑dimethylphospholano]ferrocene, 97+%

R,R-Me-Ferrocelane™C22H32FeP2FW 414.28

Fe

P

P

H3C

CH3

CH3

H3C

675601-100MG 100 mg

675601-500MG 500 mg

1,1′-Bis[(2S,5S)-2,5‑dimethylphospholano]ferrocene

S,S-Me-Ferrocelane™C22H32FeP2FW 414.28

Fe

P

P

H3C

CH3

CH3

H3C

675598-100MG 100 mg

675598-500MG 500 mg

(2R,5R)-(+)-1-(2-(1,3-Dioxolan-2-yl)phenyl)-2,5-diethyl-phospholane

8

R,R-Et-RajPhos™C17H25O2PFW 292.35

P

O

O

CH3

H3C

Fp: 230 °F

677051-100MG 100 mg

677051-500MG 500 mg

(2S,5S)-(–)-1-(2-(1,3-Dioxolan-2-yl)phenyl)-2,5-diethyl-phospholane

8

S,S-Et-RajPhos™C17H25O2PFW 292.35

P

O

O

CH3

H3C

Fp: 230 °F

677078-100MG 100 mg

677078-500MG 500 mg

(2R,5R)-1-(2-(1,3-Dioxolan-2-yl)phenyl)-2,5-dimethyl-phospholane

8

R,R-Me-RajPhos™C15H21O2PFW 264.30

P

O

O

H3C

CH3

Fp: 110 °C (230 °F)

677043-100MG 100 mg

677043-500MG 500 mg

(2S,5S)-(+)-1-(2-(1,3-Dioxolan-2-yl)phenyl-2,5-dimethylphospholane

8

S,S-Me-RajPhos™C15H21O2PFW 264.30

P

O

O

H3C

CH3

Fp: 230 °F

677035-100MG 100 mg

677035-500MG 500 mg

DuPhos/BPE Ligands Kit I 8

Components(−)-1,2‑Bis((2S,5S)-2,5‑dimethylphospholano)ethane (Aldrich 665207) 100mg(+)-1,2‑Bis[(2S,5S)-2,5‑dimethylphospholano]benzene (Aldrich 665266) 100mg(+)-1,2‑Bis((2S,5S)-2,5‑diphenylphospholano)ethane (Aldrich 667854) 100mg(−)-1,2‑Bis((2S,5S)-2,5‑diisopropylphospholano)benzene (Aldrich 668176) 100mg1,2‑Bis((2S,5S)-2,5‑diisopropylphospholano)ethane (Aldrich 668435) 100mg(−)-1,2‑Bis((2S,5S)-2,5‑diethylphospholano)ethane (Aldrich 668451) 100mg(+)-1,2‑Bis[(2S,5S)-2,5‑diethylphospholano]benzene (Aldrich 668486) 100mg1,1′-Bis[(2S,5S)-2,5‑dimethylphospholano]ferrocene (Aldrich 675598) 100mg(2S,5S)-(+)-1-(2-(1,3‑Dioxolan-2‑yl)phenyl-2,5‑dimethylphospholane (Aldrich677035) 100mg1,2‑Bis[(2S,5S)-2,5‑dimethylphospholano]benzene monooxide (Aldrich 678562)100mg1,1′-Bis((2S,5S)-2,5‑diethylphospholano)ferrocene (Aldrich 681008) 100mg1,1′-Bis[(2S,5S)-2,5‑diisopropylphospholano]ferrocene (Aldrich 684406) 100mg

JR: 11-17

687774-1KT 1 kit


DuPhosand

BPE



















catASium®—Essential Elements for Asymmetric Hydrogenations

Renat Kadyrov, Jürgen KrauterEvonik Degussa GmbH, Rodenbacher Chaussee 4, D-63457 Hanau-Wolfgang, Germany

Transition metal catalyzed enantioselective hydrogenation has beenestablished as one of the most favorable strategies for the synthesis ofoptically active compounds in academia and on the industrial scale. Inparticular, chiral ligands bearing trivalent phosphorus as the ligatingatom for “soft“ metals like rhodium(I), ruthenium(II), or iridium(I) play apivotal role in this area. Among electron-rich chiral phosphines, chiralphospholanes have emerged as one of the most efficient classes ofligands in metal catalyzed enantioselective reactions. Prominentexamples are bisphospholane ligands like DuPHOS and BPE. In general,these compounds are synthesized by a linear approach, where thephospholane is constructed by condensation of a primary phosphinewith the sulfate or sulfonates derived from the appropriate chiral diols inthe presence of strong bases. This tedious approach is restricted by lowtolerance of the functional groups and, therefore, strongly limits thepossible variations of the backbone.

Evonik Degussa GmbH has developed a modular synthesis of diversearrays of chiral vicinal bisphospholanes in collaboration with theLeibniz-Institute of Organic Catalysis in Rostock.1 These ligands, whichare now commercially available on a multikilogram scale under thetrademark catASium M, are characterized by varied “bite-angle” andelectronic properties of the bridging unit.2 The new ligands can beadvantageously employed in the fine-tuning of those enantioselectivehydrogenations, where the results obtained with traditionalbisphospholane ligands require optimization.

A rhodium(I) catalyst based on the new chiral bisphospholane ligand isone of the most effective catalytic systems for the hydrogenation ofnon-substituted and β-substituted itaconic acid derivatives known.3

The selected results (Table 1) show that this ligand displays a higherperformance as compared to the known systems. The excellentenantioselectivities (up to 99%) are combined with a high catalyticactivity (TOF up to 40,000 h-1).

Exciting results were also observed in the hydrogenation of β-acylamidoacrylates (Table 2). These are important intermediates in the synthesis ofenantiopure β-amino acids. Particularly, when the hydrogenation of thechallenging Z-configured substrates bearing bulky substituents in the3‑position (for example i-Pr) were tested, a catASium M(R)Rh-catalystshowed the highest enantioselectivities known for these substrates.A new class of atropisomeric ligands based on camphor catASium Tweredeveloped in close collaboration with Russian researchers. The newligand system combines the features of central chirality derived from anatural product with axial chirality like in the biaryl type ligands. Inaddition to this, the two phosphorus groups are introduced sequentiallyleading to a large variety of tuneable ligands.4

The selected results of hydrogenation of (Z)- and (E)-methyl3‑acetylamino-2‑butenoates are summarized in Table 2. Excellentenantiomeric excesses of >99% were reached by hydrogenation of theE-isomer. Noteworthy is the 94% ee achieved using catASium T2 catalystin the hydrogenation of the Z-isomer. It is one of the best opticalinductions achieved in the hydrogenation of the Z-β-enamides. Theseligands also show interesting properties in the hydrogenation ofchallenging simple α-enamides (Table 3).

Whereas applying catalysts based on catASium T ligands to electron-richsubstrates induce only moderate enantiomeric excesses, thehydrogenation of the substrate with electron-withdrawing groupssurprisingly leads to near complete enantioselectivity.

Cationic catalyst catASium DRh, with a ligand well known under theold name Deguphos, was successfully utilized in the first highlyenantioselective reductive amination of keto acids, where several chiralα-amino acids were produced in good yield and very high ee's(up to 98%) (Table 4).5

References: (1) Holz, J.; Monsees, A.; Jiao, H.; You, J.; Komarov, I. V.; Fischer, C.; Drauz, K.;Börner, A. J. Org. Chem. 2003, 68, 1701‑1707. (2) Holz, J.; Zayas, O.; Jiao, H.; Baumann,W.; Spannenberg, A.; Monsees, A.; Riermeier, T. H.; Almena, J.; Kadyrov, R.; Börner, A.Chem. -Eur. J. 2006, 12, 5001‑5013. (3) Almena, J.; Monsees, A.; Kadyrov, R.; Riermeier, T.H.; Gotov, B.; Holz, J.; Börner, A. Adv. Synth. Catal. 2004, 346, 1263‑1266. (4) Kadyrov, R.;Ilaldinov, I. Z.; Almena, J.; Monsees, A.; Riermeier, T. H. Tetrahedron Lett. 2005, 46,7395‑7400. (5) Kadyrov, R.; Riermeier, T. H.; Dingerdissen, U.; Tararov, V.; Börner, A. J. Org.Chem. 2003, 68, 4067‑4070.

O

OOR'

OR

O

OOR'

OR

catASium® / Rh

Catalyst R R’ Solvent TON ee (%)

catASium® M(R)Rh H Me CH2Cl2 10,000 99

catASium® M(R)Rh H H CH2Cl2 4,000 99

catASium® MN(R)Rh Ph H Acetone 500 98

catASium® MNBn(R)Rh i-Pr H CH3OH 500 98

Table 1. Hydrogenation of β-substituted itaconic acid derivatives

catASium® / Rh

(S)

NHAc

RCOOR'

NHAc

RCOOR'

Catalyst Confi guration R R’ Solvent ee (%)

catASium® M(R)Rh E Me Bn CH2Cl2 99.5

catASium® M(R)Rh Z Me Bn CH3OH 89.9

catASium® M(R)Rh E i-Pr Et CH2Cl2 99.7

catASium® M(R)Rh Z i-Pr Et CH2Cl2 89.6

catASium® T2(R)/Rh E Me Me CH3OH 99.3

catASium® T2(R)/Rh Z Me Me CH2Cl2 94

Table 2. Enantioselective hydrogenationsof β-enamides using catASium® ligands

catASium® / Rh

R

NHAc NHAc

R (R)

R ligand Solvent ee (%)

t-Bu catASium® T1 CH2Cl2 87

Ph catASium® T2 MeOH 92

3-NO2C6H4 catASium® T2 toluene 99.7

2-naphthyl catASium® T2 toluene 98

Table 3. Enantioselective hydrogenation of enamidesusing Rh(I)-complexes of catASium® T

R COOH

O

COOH

NHBncatASium® D(R)Rh

R (S)BnNH2, H2

R Product Isolated Yield ee (%)

Me N-Bn-Ala 43 78

PhCH2 N-Bn-Phe 99 98

PhCH2CH2 N-Bn-Bn-Ala 79 81

Me2CHCH2 N-Bn-Leu 99 90

Me3CCH2 N-Bn-t-Bu-Ala 94 86

Table 4. Yields and enantioselectivities of the reductive aminationof α-keto acids with benzylamine using catASium® D(R)Rh


catA

Sium

®


D-type

(+)-N-Benzyl-(3R,4R)-bis(diphenylphosphino)pyrrolidine, 98%

8

(+)-(3R,4R)-3,4-Bis(diphenylphosphino)-1-benzyl-pyrrolidine; (3R,4R)-1-Benzyl-3,4-bis-diphenylphos-phanyl-pyrrolidine; catASium® D(R)[99135‑95‑2]C35H33NP2FW 529.59

N

PP

≥98% (31P-NMR)

LR: 36 S: 26

672653-100MG 100 mg

672653-500MG 500 mg

(+)-1-Benzyl-[(3R,4R)-bis(diphenylphosphino)]pyrrolidine(1,5-cyclooctadiene)rhodium(I) tetra-fluoroborate, 98%

8

(3R-trans)-3,4-Bis(diphenylphosphino)-1-(phenylmethyl)pyrrolidine rhodium complex;catASium® D(R)Rh[99143‑48‑3]C43H45BF4NP2RhFW 827.48

Rh

P

P

N

BF4

≥98% (31P-NMR)

LR: 36/37/38 S: 26

672777-100MG 100 mg

672777-500MG 500 mg

M-type

2,3-Bis[(2R,5R)-2,5-dimethylphospholano]-N-benzyl-maleimide(1,5-cyclooctadiene)rhodium(I) tetrafluoro-borate, 95%

8

3,4-Bis[(2R,5R)-2,5-dimethylphospholanyl]-1-benzyl-1H-pyrrol-2,5-dion(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate; catASium® MNBn(R)RhC31H43BF4NO2P2RhFW 713.34

P

P

Rh+

CH3

H3C CH3

H3C

N

O

O

BF4-

≥95% (31P-NMR)

LR: 36/37/38 S: 26

669709-100MG 100 mg

669709-500MG 500 mg

2,3-Bis[(2R,5R)-2,5-dimethylphospholano]-N-[3,5-bis(trifluoromethyl)-phenyl]maleimide, 98%

8

3,4-Bis[(2R,5R)-2,5-dimethylphospholanyl]-1-[3,5-bis(trifluormethyl)phenyl]-1H-pyrrol-2,5-dione;catASium® MNXylF(R)C24H27F6NO2P2FW 537.41 P

H3C

CH3

N

O

O

P

CH3

H3C

CF3

CF3

≥98% (31P-NMR)

LR: 36/37/38 S: 26

670030-100MG 100 mg

670030-500MG 500 mg

(−)-2,3-Bis[(2R,5R)-2,5-dimethylphospholano]-N-[3,5-bis(trifluoromethyl)phenyl]maleimide(1,5-cycloocta-diene)rhodium(I) tetrafluoroborate, 98%

8

3,4-Bis[(2R,5R)-2,5-dimethylphospholanyl]-1-[3,5-di(trifluoromethyl)phenyl]-1H-pyrrol-2,5-dion(1,5-cyclooctadiene)rhodium(I) tetra-fluoroborate; catASium® MNXylF(R)RhC32H39BF10NO2P2RhFW 835.31

P

P

Rh+

CH3

H3C CH3

H3C

N

O

O

BF4-

CF3

CF3

≥98% (31P-NMR)

670154-100MG 100 mg

670154-500MG 500 mg

(−)-4,5-Bis[(2R,5R)-2,5-dimethylphospholano]-1,2-di-hydro-1,2-dimethyl-3,6-pyridazinedione(1,5-cyclo-octadiene)rhodium(I) tetrafluoroborate, 95%

8

{4,5-Bis[(2R,5R)-2,5-dimethylphospholanyl]-1,2-dimethyl-1,2-dihydropyridazine-3,6-dione}(1,5-cyclooctadiene)rhodium(I) tetra-fluoroborate; catASium® MNN(R)Rh[908128‑78‑9]C26H42BF4N2O2P2RhFW 666.28

Rh

P

PH3C

H3C

BF4

NN

O

O

CH3

CH3

CH3

CH3

≥95% (31P-NMR)

670588-100MG 100 mg

670588-500MG 500 mg

2,3-Bis[(2R,5R)-2,5-dimethylphospholano]-N-(3,5-dimethylphenyl)maleimide, 98%

8

3,4-Bis[(2R,5R)-2,5-dimethylphospholanyl]-1-(3,5-dimethylphenyl)-1H-pyrrol-2,5-dione; catASium®

MNXyl(R)C24H33NO2P2FW 429.47 P

H3C

CH3

N

O

O

P

CH3

H3C

CH3

CH3

≥98% (31P-NMR)

669814-100MG 100 mg

669814-500MG 500 mg

(−)-2,3-Bis[(2R,5R)-2,5-dimethylphospholano]-N-(3,5-dimethylphenyl)maleimide(1,5-cyclooctadiene)rhodi-um(I) tetrafluoroborate, 95%

8

3,4-Bis[(2R,5R)-2,5-dimethylphospholanyl]-1-(3,5-dimethylphenyl]-1H-pyrrol-2,5-dion(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate;catASium® MNXyl(R)RhC32H45BF4NO2P2RhFW 727.36

P

P

Rh+

CH3

H3C CH3

H3C

N

O

O

BF4-

CH3

CH3

≥95% (31P-NMR)

LR: 36/37/38 S: 26

669938-100MG 100 mg

669938-500MG 500 mg


catA

Sium

®


















(−)-2,3-Bis[(2R,5R)-2,5-dimethylphospholano]maleicanhydride, 98%

8

3,4-Bis[(2R,5R)-2,5-dimethyl-1-phospholanyl]furan-2,5-dione; catASium® M(R)[505092‑86‑4]C16H24O3P2FW 326.31 P

H3C

CH3

O

O

O

P

CH3

H3C

≥98% (31P-NMR)

670693-100MG 100 mg

670693-500MG 500 mg

(−)-2,3-Bis[(2R,5R)-2,5-dimethylphospholano]maleicanhydride(1,5-cyclooctadiene)rhodium(I) tetrafluoro-borate, 98%

8

2,3-Bis[(2R,5R)-2,5-dimethyl-phospholanyl]maleicanhydride(1,5-cyclooctadiene)rhodium(I) tetra-fluoroborate; catASium® M(R)Rh[507224‑99‑9]C24H36BF4O3P2RhFW 624.20

Rh

P

P

CH3

H3C CH3

H3C

O

O

O

BF4

≥98% (31P-NMR)

670804-100MG 100 mg

670804-500MG 500 mg

(−)-2,3-Bis[(2R,5R)-2,5-dimethylphospholano]-N-(4-methoxyphenyl)maleimide(1,5-cyclooctadiene)rhodi-um(I) tetrafluoroborate, 98%

8

P

P

Rh+

CH3

H3C CH3

H3C

N

O

O

BF4-

OCH3

3,4‑Bis[(2R,5R)-2,5‑dimethylphospholanyl]-1-(4‑methoxyphenyl)-1H-pyrrol-2,5‑dion(1,5‑cyclooctadiene)rhodium(I) tetrafluoroborate;catASium® MNAn(R)RhC31H43BF4NO3P2RhFW 729.34≥98% (31P-NMR)

670251-100MG 100 mg

670251-500MG 500 mg

(−)-2,3-Bis[(2R,5R)-2,5-dimethylphospholano]-N-methylmaleimide(1,5-cyclooctadiene)rhodium(I)tetrafluoroborate, 98%

8

2,3-Bis[(2R,5R)-2,5-dimethylphospholanyl]malein-N-methylimide(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate; catASium® MN(R)Rh[821793‑41‑3]C25H39BF4NO2P2RhFW 637.24

P

P

Rh+

CH3

H3C CH3

H3C

N

O

O

CH3

BF4-

≥98% (31P-NMR)

LR: 36/37/38 S: 26

669598-100MG 100 mg

669598-500MG 500 mg

2,3-Bis[(2R,5R)-2,5-dimethylphospholano]-N-(penta-fluorophenyl)maleimide(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate, 95%

8

P

P

Rh+

CH3

H3C CH3

H3C

N

O

O

BF4

F

F F

FF

3,4‑Bis[(2R,5R)-2,5‑dimethylphospholanyl]-1‑pentafluorophenyl-1H-pyrrole-2,5‑dione(1,5‑cyclooctadiene)rhodium(I) tetrafluoroborate;catASium® MNF(R)RhC30H36BF9NO2P2RhFW 789.26≥95% (31P-NMR)

670367-100MG 100 mg

670367-500MG 500 mg

1,2-Bis[(2R,5R)-2,5-dimethylphospholano]-3,3,4,4-tetrafluoro-1-cyclobutene(1,5-cyclooctadiene)rhodi-um(I) ) tetrafluoroborate, 95%

8

1,2-Bis[(2R,5R)-2,5-dimethyl-phospholanyl]3,3,4,4-tetrafluoro-1-cyclobutene(1,5-cyclo-octadiene)rhodium(I) tetrafluoroborate;catASium® MQF(R)Rh[910048‑20‑3]C24H36BF8P2RhFW 652.19

P

P

Rh+

CH3

H3C CH3

H3C

BF4-

FF

FF

≥95% (31P-NMR)

670472-100MG 100 mg

670472-500MG 500 mg


catA

Sium

®














T-type

(1R,aR)-3-Diphenylphosphino-2-(4-bis(3,5-dimethyl-phenyl)phosphino-2,5-dimethyl-3-thienyl)-1,7,7-tri-methylbicyclo[2.2.1]hept-2-ene, 99%

8

3-[Bis(3,5-dimethylphenyl)phosphanyl]-4-[(1R,4S)-3-diphenylphosphanyl-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-en-2-yl]-2,5-dimethylthio-phene; catASium® T3(R)[868851‑50‑7]C44H48P2SFW 670.86

P

S

CH3

CH3

P

CH3

H3C CH3

H3C

CH3

H3C CH3

H

≥99% (31P-NMR)

671258-100MG 100 mg

671258-500MG 500 mg

(1R,aR)-3-[Bis(3,5-dimethylphenyl)phosphino]-2-(4-diphenylphosphino-2,5-dimethyl-3-thienyl)-1,7,7-tri-methylbicyclo[2.2.1]hept-2-ene, 99%

8

3-{(1R,4S)-3-[Bis(3,5-dimethylphenyl)phospha-nyl]-1,7,7-trimethylbicyclo[2.2.1]hept-2-en-2-yl}-4-diphenylphosphanyl-2,5-dimethylthiophene;catASium® T2(R)[868851‑48‑3]C44H48P2SFW 670.86

P

S

CH3

CH3

P

CH3

H3C CH3

H3C CH3

CH3

CH3

H

≥99% (31P-NMR)

671142-100MG 100 mg

671142-500MG 500 mg

(1R,aR)-3-Diphenylphosphino-2-(4-diphenylphos-phino-2,5-dimethyl-3-thienyl)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-en, 99%

8

3-Diphenylphosphanyl-4-[(1R,4S)-3-diphenylphospha-nyl-1,7,7-trimethylbicyclo[2.2.1]hept-2-en-2-yl]-2,5-dimethylthiophene; catASium® T1(R)[868851‑47‑2]C40H40P2SFW 614.76

P

S

CH3

CH3

P

CH3

H3C CH3

H

≥99% (31P-NMR)

671029-100MG 100 mg

671029-500MG 500 mg

Kit

Evonik Ligand Kit for Asymmetric Hydrogenations 8

catASium® Ligand Toolbox

Components(+)-N-Benzyl-(3R,4R)-bis(diphenylphosphino)pyrrolidine (Aldrich 672653)(+)-1‑Benzyl-[(3R,4R)-bis(diphenylphosphino)]pyrrolidine(1,5‑cyclooctadiene)rhodi-um(I) tetrafluoroborate (Aldrich 672777)(1R,aR)-3‑Diphenylphosphino-2-(4‑bis(3,5‑dimethylphenyl)phosphino-2,5‑dimethyl-3‑thienyl)-1,7,7‑trimethylbicyclo[2.2.1]hept-2‑ene (Aldrich 671258)(1R,aR)-3-[Bis(3,5‑dimethylphenyl)phosphino]-2-(4‑diphenylphosphino-2,5‑dimeth-yl-3‑thienyl)-1,7,7‑trimethylbicyclo[2.2.1]hept-2‑ene (Aldrich 671142)(1R,aR)-3‑Diphenylphosphino-2-(4‑diphenylphosphino-2,5‑dimethyl-3‑thienyl)-1,7,7‑trimethyl-bicyclo[2.2.1]hept-2‑en (Aldrich 671029)(−)-2,3‑Bis[(2R,5R)-2,5‑dimethylphospholano]maleic anhydride(1,5‑cyclooctadiene)rhodium(I) tetrafluoroborate (Aldrich 670804)(−)-2,3‑Bis[(2R,5R)-2,5‑dimethylphospholano]maleic anhydride (Aldrich 670693)(−)-4,5‑Bis[(2R,5R)-2,5‑dimethylphospholano]-1,2‑dihydro-1,2‑dimethyl-3,6‑pyrida-zinedione(1,5‑cyclooctadiene)rhodium(I) tetrafluoroborate (Aldrich 670588)1,2‑Bis[(2R,5R)-2,5‑dimethylphospholano]-3,3,4,4‑tetrafluoro-1‑cyclobutene(1,5‑cy-clooctadiene)rhodium(I) ) tetrafluoroborate (Aldrich 670472)2,3‑Bis[(2R,5R)-2,5‑dimethylphospholano]-N-(pentafluorophenyl)maleimide(1,5‑cy-clooctadiene)rhodium(I) tetrafluoroborate (Aldrich 670367)(−)-2,3‑Bis[(2R,5R)-2,5‑dimethylphospholano]-N-(4‑methoxyphenyl)maleimide(1,5‑cyclooctadiene)rhodium(I) tetrafluoroborate (Aldrich 670251)(−)-2,3‑Bis[(2R,5R)-2,5‑dimethylphospholano]-N-[3,5‑bis(trifluoromethyl)phenyl]mal-eimide(1,5‑cyclooctadiene)rhodium(I) tetrafluoroborate (Aldrich 670154)2,3‑Bis[(2R,5R)-2,5‑dimethylphospholano]-N-[3,5‑bis(trifluoromethyl)-phenyl]malei-mide (Aldrich 670030)(−)-2,3‑Bis[(2R,5R)-2,5‑dimethylphospholano]-N-(3,5‑dimethylphenyl)maleimide(1,5‑cyclooctadiene)rhodium(I) tetrafluoroborate (Aldrich 669938)2,3‑Bis[(2R,5R)-2,5‑dimethylphospholano]-N-(3,5‑dimethylphenyl)maleimide (Al-drich 669814)2,3‑Bis[(2R,5R)-2,5‑dimethylphospholano]-N-benzylmaleimide(1,5‑cyclooctadiene)rhodium(I) tetrafluoroborate (Aldrich 669709)(−)-2,3‑Bis[(2R,5R)-2,5‑dimethylphospholano]-N-methylmaleimide(1,5‑cycloocta-diene)rhodium(I) tetrafluoroborate (Aldrich 669598)

LR: 36/37/38 S: 26

672556-1KT 1 kit


catA

Sium

®









P-Phos, PhanePhos and BoPhoz™ Ligands

N

N

OCH3

H3COH3CO

OCH3

PAr2

PAr2

P-Phos

The P-Phos ligand family was developed by Professor Chan of HongKong Polytechnic University and licensed to JM CCT in 2002. P-Phos is anatropisomeric biaryl bisphosphine with the unique feature ofincorporating two methoxy-substituted pyridine rings in the backbone.1

This family of ligands often presents higher activity and selectivity thanthe analogous BINAP ligands in a series of reactions such as rutheniumcatalyzed hydrogenation of β-ketoesters2 (Scheme 1) and rhodium- andruthenium-catalyzed hydrogenation of dehydroamino acids(Scheme 2).3 Ru catalyzed hydrogenation of non-functionalizedketones is also highly effective using P-Phos ligands.4 Moreover, JMhas further developed the scope of P-Phos Ru diamine complexes inketone hydrogenation by the application of less traditional 1,3- and1,4‑diamines (Scheme 3).5 Iridium-P-Phos catalysts have beenrecently used for the asymmetric hydrogenation of C=N bonds inquinolines (Scheme 4).6

PAr2

PAr2

Phanephos

Phanephos was first reported in 1997, and since then it has foundapplications in the rhodium-catalyzed hydrogenation of dehydroaminoacids7 (Scheme 5) and the ruthenium-catalyzed hydrogenation ofβ-ketoesters (Scheme 6).8 Both rhodium and ruthenium catalystsbearing the Phanephos ligand show an exceptionally high activity in mosthomogeneous hydrogenation reactions.

R1

O

OR2

O [L*-Ru(C6H6)Cl]Cl

EtOH/CH2Cl24 - 25 atm H2

70 - 90 oC, 1-24 h

R1

OH

OR2

O

*

H3C

OH

OC2H5

O

* H3C

OH

OCH2Ph

O

* ClH2C

OH

OC2H5

O

*

(S)-P-Phos S/C 400, 98.6% ee S/C 2800, 96.6% ee S/C 2800, 98.0% ee(R)-Tol-P-Phos S/C 400, 98.0% ee S/C 400, 98.0% ee S/C 400, 97.9% ee(R)-Xyl-P-Phos S/C 400, 97.1% ee S/C 2800, 94.5% ee S/C 400, 94.8% ee

Scheme 1

CO2Me

NHCOMeR

[L*-Ru(C6H6)Cl]Cl, 1 atm H2

MeOH, rt, 3-10 h, S/C 100

[L*-Rh(COD)]BF4, 1 atm H2

MeOH, 0 oC, 18 h, S/C 100

CO2Me

NHCOMeR

CO2Me

NHCOMeR

CO2Me

NHCOMe

Cl

Ru-(R)-P-Phos 97% ee 91% ee 90% eeRh-(R)-Xyl-P-Phos 90% ee 94% ee 90% ee

CO2Me

NHCOMeMe

CO2Me

NHCOMeMeO

Scheme 2

R

O

R1

RuCl2[(R)-Xyl-P-Phos][(R,R)-DPEN]

2-propanol, KOtBu rt, 6 - 55 atm H2, 2 - 48 h

R

OH

R1*

X OHX S/C ee

H 100,000 99.1Me 4000 97.7OMe 4000 93.3Br 10000 >99.9

Scheme 3

N R

[Ir(COD)Cl]2/(R)-P-Phos/I2

rt, 20 h, 47 atm H2, THFS/[Ir]/L*/I2 = 100:0.5:1.1:10

NH

R

NH

Me NH

OH

NH

Me

F

ee 91% 90% 91%isolated yield 97% 90% 99%

Scheme 4

R1 R2

PHNOMe

O

[(S)-Phanephos Rh]OTf

MeOH, 1.5 atm H2

R1 R2

PHNOMe

O*

R1 R2 P ee (%)H H Ac 99.6 (R)Ph H Ac 98 (R)Ph H Bz 97 (R)H H Cbz 91 (R)

Scheme 5

R

O

OR'

O (S)-Phanephos Ru(TFA)2

Bu4NI, MeOH/H2O (10:1)3.5 atm H2, 18 h

R OR'*

R = R' = Me 96% ee (R)R = Me, R' = tBu 95% ee (R)R = Et, R' = Me 95% ee (R)R = iPr, R' = Et 95% ee (S)

OH

Scheme 6


P-Phos,

PhanePhosand

BoPhoz™

Ligands


Fe

BoPhozTM

PR2

NPR2

R

The BoPhoz class of ligands, based on the ferrocene backbone, haveproven to be exceptionally active in many rhodium-catalyzedhydrogenations9 as well as being used in a number of ruthenium-catalyzed reactions. More recently Johnson-Matthey has developed newvariants of BoPhoz ligands that offer increased structural and electronicdiversity that may be required for the desired transformation. MeBoPhozhas shown excellent activity in many rhodium-catalyzed asymmetrichydrogenation of C=C bonds in dehydroaminoacids andα,β-unsaturated acids and esters (s/c up to 100,000) (Scheme 7).10

The P-Cy-Me-BoPhoz ligand has been shown to catalyze the asymmetricreduction of α-ketoesters, which is unusual for a rhodium catalyst(Scheme 8).

References: (1) Wu, J.; Chan, A. S. C. Acc. Chem. Res., 2006, 39, 711. (2) Wu, J. et al.Tetrahedron Lett. 2002, 43, 1539. (3) Wu, J. et al. Tetrahedron: Asymmetry 2003, 14, 987.(4)(a) Wu, J. et al. J. Org. Chem. 2002, 67, 7908. (b) Wu, J. et al. Chem. -Eur. J. 2003, 9,2963. (5)(a) Hems, W. P. et al. Acc. Chem. Res. 2007, 40, 1340. (b) Grasa, G. A. et al. J.Organomet. Chem. 2006, 691, 2332. (c) Grasa, G. A. et al. Org. Lett. 2005, 7, 1449.(6) Xu, L. et al. Chem. Commun. 2005, 1390. (7) Rossen, K. et al. J. Am. Chem. Soc. 1997,119, 6207. (8) Pye, P. J. et al. Tetrahedron Lett. 1998, 39, 4441. (9)(a) Boaz, N.W. et al. Org.Lett. 2002, 4, 2421. (b) Boaz, N.W. J. Org. Chem. 2005, 70, 1872. (10) Boaz, N.W. Org.Proc. Res. Dev. 2005, 9, 472.

RCO2R'

NHR''R

CO2R'

NHR''

[(COD)2Rh]OTf, (R,S)-MeBoPhoz

rt, THF, 10 psi H2

PhNHAc

CO2MePh

NHBoc

CO2Me

NHAc

CO2Me

NC NHCbz

CO2MePh

99.1% ee 91.5% ee 99% ee 98.1% ee

Scheme 7

CO2R'R

CO2R'


rt, MeOH, 300 psi H2

CO2R'R

CO2R'

R = H, R' = H 97.6% eeR = H, R' = CH3 94% eeR = Ph, R' = H 90% ee

R CO2R'

O


rt, 300 psi H2, S/C 1000:1

R CO2R'

OH

R R' Solvent TOF e e (%)

CH3 CH3 9:1 EtOAc/THF 2100 86.6CH3 CH3 MeOH 750 75.4CH3 CH2CH3 9:1 EtOAc/THF 4440 91.6PhCH2CH2 CH2CH3 9:1 EtOAc/THF 580 80.2

CH3 CH3 9:1 EtOAc/THF 3360 89.6CH3 CH3 MeOH 2350 11.2CH3 CH2CH3 9:1 EtOAc/THF 6220 91.6PhCH2CH2 CH2CH3 9:1 EtOAc/THF 4370 90.2

Fe

FePPh2

NPCy2

Me

PPh2

NPPh2

Me

Scheme 8

(R)-(–)-4,12-Bis(diphenylphosphino)-[2.2]-paracyclo-phane, 96%

8

(R)-Phanephos[364732‑88‑7]C40H34P2FW 576.65 PPh2

PPh2

LR: 37

682144-100MG 100 mg

682144-500MG 500 mg

(S)-(+)-4,12-Bis(diphenylphosphino)-[2.2]-paracyclo-phane, 96%

8

(S)-Phanephos[192463‑40‑4]C40H34P2FW 576.65

PPh2

PPh2

LR: 37

682136-100MG 100 mg

682136-500MG 500 mg

(R)-(–)-4,12-Bis[di(3,5-xylyl)phosphino]-[2.2]-para-cyclophane, 97%

8

PR2PR2

R=

CH3

CH3

(R)-Xylyl-PHANEPhos; (R)-5,11‑Bis(3,5‑xylylphosphino)tricyclo[8.2.2.24,7]hexadeca-hexaene[325168‑89‑6]C48H50P2FW 688.86

LR: 36/38 S: 26

682306-100MG 100 mg

682306-500MG 500 mg

(S)-(+)-4,12-Bis[di(3,5-xylyl)phosphino]-[2.2]-para-cyclophane, 97%

8

(S)-xylyl-PHANEPHos; (S)-5,11-Bis(3,5-xylyl-phosphino)tricyclo[8.2.24,7]hexadeca-hexaene[325168‑88‑5]C48H50P2FW 688.86

PR2

PR2

R=

CH3

CH3

LR: 36/38 S: 26

682292-100MG 100 mg

682292-500MG 500 mg


P-Phos,

PhanePhosand

BoPhoz™

Ligands










(R)-N-Methyl-N-diphenylphosphino-1-[(S)-2-diphenyl-phosphino)ferrocenyl]ethylamine

8

Methyl-BoPhoz; (1R)-1-(Diphenylphosphino)-2-[(1R)-1-[(diphenylphosphino)methylamino]ethyl]ferrocene[406680‑94‑2]C37H35FeNP2FW 611.47

FePN

CH3

P

CH3

682322-100MG 100 mg

682322-500MG 500 mg

(S)-N-Methyl-N-diphenylphosphino-1-[(R)-2-(diphenyl-phosphino)ferrocenyl]ethylamine

8

Methyl-BoPhoz; (1S)-1-(Diphenylphosphino)-2-[(1S)-1-[(diphenylphosphino)methylamino]ethyl]ferrocene[406681‑09‑2]C37H35FeNP2FW 611.47

PN

P

H3C

H3C

Fe

682314-100MG 100 mg

682314-500MG 500 mg

(R)-(+)-2,2′,6,6′-Tetramethoxy-4,4′-bis(diphenylphosphino)-3,3′-bipyridine, 97%

(R)-P-Phos[221012‑82‑4]C38H34N2O4P2FW 644.64

N

N

OCH3

OCH3

H3COH3CO PPh2

PPh2

675806-100MG 100 mg

675806-500MG 500 mg

(S)-(−)-2,2′,6,6′-Tetramethoxy-4,4′-bis(diphenylphosphino)-3,3′-bipyridine, 97%

(S)-P-Phos[362524‑23‑0]C38H34N2O4P2FW 644.64

N

N

OCH3

OCH3

H3COH3CO PPh2

PPh2

LR: 37

675792-100MG 100 mg

675792-500MG 500 mg

(R)-(+)-2,2′,6,6′-Tetramethoxy-4,4′-bis(di(3,5‑xylyl)phos-phino)-3,3′-bipyridine, 97%

(R)-Xylyl-P-Phos[442905‑33‑1]C46H50N2O4P2FW 756.85

N

N

H3CO

H3CO

H3CO

H3CO

P

CH3

CH3

P

CH3

CH3

CH3H3C

H3C CH3

LR: 36/37/38 S: 26

676004-100MG 100 mg

676004-500MG 500 mg

(S)-(−)-2,2′,6,6′-Tetramethoxy-4,4′-bis[di(3,5‑xylyl)phos-phino]-3,3′-bipyridine, 97%

(S)-Xylyl-P-Phos[443347‑10‑2]C46H50N2O4P2FW 756.85

N

N

H3CO

H3CO

H3CO

H3CO

P

CH3

CH3

P

CH3

CH3

CH3H3C

H3C CH3

LR: 36/37/38 S: 26-36

675946-100MG 100 mg

675946-500MG 500 mg


P-Phos,

PhanePhosand

BoPhoz™

Ligands














ChiralQuest Phosphine Ligands and Complexes

Professor Xumu Zhang at Penn State has made remarkable advances bycreating a toolbox of chiral phosphines which can be used on a variety ofsubstrates, some of which have been historically resistant to facilehydrogenation. Furthermore, an additional benefit in some reductions isreduced catalyst loading, due to increased turnover numbers (TON).1

(S)-C3‑TunePhosC3‑TunePhos, a member of the atropisomeric aryl bisphosphine ligandfamily with tunable dihedral angles, provides comparable or superiorenantioselectivities and catalytic abilities to BINAP in Ru-catalyzedasymmetric hydrogenation of β-keto esters (Scheme 1),2 cyclicβ-(acylamino) acrylates (Scheme 2),3 and α-phthalimide ketones(Scheme 3).4

(1S,1S',2R,2R')-TangPhosA highly electron-donating, low molecular weight, and rigid P-chiralbisphospholane ligand, TangPhos proved to be incredibly efficient in therhodium-catalyzed hydrogenation of a variety of functionalized olefinssuch as α-dehydroamino acids,5 arylenamides,5 β-(acylamino)acrylates,6

itaconic acids,7 and N-tosylimines8 (Scheme 4).

This P-chiral phosphorus ligand represents a superior ligand forasymmetric catalysis including hydrogenation because of its ability toforce the chiral environment to encompass the substrate in closeproximity to the reactive metal center. TangPhos exhibits substantialconformational rigidity allowing for high enantioselectivities in thehydrogenation of a wide variety of densely functionalized prochiralolefins, with some reaction examples approaching 100% ee.

(S)-BINAPINEBINAPINE, a highly electron-donating rigid ligand, demonstrates excellentenantioselectivity and reactivity, with TON up to 10,000 for theasymmetric hydrogenation of Z-β-aryl(β-acylamino) acrylates(Scheme 5).9 Interestingly, BINAPINE is a rare example of abisbinaphthophosphepine ligand with P-chiral phosphine atoms. Highenantioselectivities have been obtained with substrates that containdiverse substituents ranging from electron-rich and electron-pooraryl groups to heteroaryl components. This catalyst system illustratesthe incredible effects of rigidity on the stereocontrol in thehydrogenation reaction.

(R)-BINAPHANEBINAPHANE incorporates a bisphosphinite backbone that displaysrestricted orientation of the aromatic groups proximate to thephosphines. Zhang and co-workers can tune BINAPHANE by modifyingthe groups on the aromatic and/or the phosphine, thus creating ageneral catalytic system useful for obtaining high enantioselectivities inthe asymmetric hydrogenation reaction. This ligand demonstratedexcellent enantioselectivity (up to >99% ee) for hydrogenation ofE/Z-isomeric mixtures of β-substituted arylenamides (Scheme 6).10

BINAPHANE also proved to be a very good ligand for the palladiumcatalyzed enantioselective cyclization of silyloxy-1,6‑enynes.11 This novelreaction allows for the synthesis of precursors for naturally occurringmolecules. Using mild conditions and 5 mol% of catalyst, Toste et al.reported good yields and good selectivities (Scheme 7).

(1R,1'R,2S,2'S)-DuanPhosDuanPhos is more rigid than the related TangPhos ligand, due to thefused phenyl rings on the phospholane architecture. This self-imposedconformational stability improves the enantioselectivity in thehydrogenations of a diverse array of functionalized olefins. Furthermore,Zhang and co-workers have successfully synthesized both enantiomers ofthis electron-rich ligand through a trivial resolution process. Even highlyelectron-rich prochiral olefins are readily hydrogenated with exceptionalstereocontrol by this productive Rh-catalyst system (Scheme 8).

References: (1) Zhang, W. et al. Acc. Chem. Res. 2007 40, 1278. (2) Zhang, Z. et al. J. Org.Chem. 2000, 65, 6223. (3) Tang, W. et al. J. Am. Chem. Soc. 2003, 125, 9570. (4) Lei, A. etal. J. Am. Chem. Soc. 2004, 126, 1626. (5) Tang, W.; Zhang, X. Angew. Chem., Int. Ed.Engl. 2002, 41, 1612. (6) Tang, W.; Zhang, X. Org. Lett. 2002, 4, 4159. (7) Tang, W. et al.Org. Lett. 2003, 5, 205. (8) Yang, Q. et al. Angew. Chem., Int. Ed. 2006, 45, 3832.(9) Tang, W. et al. Angew. Chem., Int. Ed. Engl. 2003, 42, 3509. (10) Xiao, D. et al. Org.Lett. 1999, 1, 1679. (11) Corkey, B. K.; Toste, F. D. J. Am. Chem. Soc. 2007, 129, 2764.

Ru[(R)-C3-TunePhos]Cl2(DMF)n (0.5 mol %)

MeOH, 60 oC, 750 psi H2

Up to 99% ee

R1 OR2

O O

R1 OR2

OH O

OEt

O O Ru(ArH)[(R)-C3-TunePhos]Cl2

EtOH, 100 oC, 6 atm H297% eeTON = 45,000

Lipitor Side Chain

Cl OEt

OH OCl *

OO PPh2

PPh2

C3-TunePhos

Scheme 1

In-situ 5 mol% Ru(COD)(Met)2

5 mol% (S)-C3-TunePhos10 mol% HBF4

MeOH, 50 atm H2, rtup to 99% ee

X

CO2RAcHN

X

CO2RAcHN

Scheme 2

2 mol%[NMe2H2][[RuCl((S)-C3-TunePhos)]2(μ-Cl)3]

EtOH, 100 bar H2

up to >99% ee

N

O

O

RO

N

O

O

RHO

Scheme 3

P P

H

H

C(CH3)3(H3C)3C

R OR'NHAc

O

>99% ee

OCH3

NHAc

O

S

>99% ee

Ar NHAc

R

>99% ee

R NHAc

O

OR'

>99% ee

R'OOH

O

OR

>99% ee

R R'

HNTosyl

>99% ee

Scheme 4


Chira

lQuest

Phosp

hine

Ligandsand

Complexes


P

tBu

PtBu

H

H

[Rh(NBD)((S)-BINAPINE)]SbF6

H2 (20 psi), rt, THF, 24 hUp to 10,000 turnovers

(Z)

Ar NHAcAr NHAc

O

OCH3

O

OCH3

BINAPINE

(S)

Up to >99% ee

Scheme 5

P P

1 mol % Rh-(R)-BINAPHANE

H2 (20 psi), rt, CH2Cl2, 24 h

Up to 99.5% ee

Ar NHAc

R

Ar NHAc

R

BINAPHANE

(S)

Scheme 6

OR2

R1

R3

(R)-Binaphane-Pd(OH2)2(OTf)2

Et2O / AcOH

O

R1R3

O

N

OBn

83%, 89% ee

O

91%, 87% ee

BzN

O

80%, 98% ee

N

OCH3Bz

CH3

79%, 80% ee

Scheme 7

P P

H

HtButBu

H2 (20 psi), rt, 2 h, MeOHTON = 10,000TOF = 5,000

Rh-(S,S,R,R)-DuanPhos

Rh-(S,S,R,R)-DuanPhos

MeOH, H2(1.3 atm), rt

96% ee

DuanPhos

COOMe

NHAc

COOMe

NHAc

OAc

MeO

100% conv, >99% ee

OAc

MeO

Scheme 8

(R)-BINAPHANE

P P

(R,R)-1,2‑Bis[(R)-4,5‑dihydro-3H-binaphtho(1,2-c:2',1'-e)phosphepino]benzene[253311‑88‑5]C50H36P2FW 698.77

650854-100MG 100 mg

650854-500MG 500 mg

(S)-BINAPINE

(3S,3'S,4S,4'S,11bS,11'bS)-(+)-4,4'-Di-t-butyl-4,4',5,5'-tetrahydro-3,3'-bi-3H-dinaphtho[2,1-c:1',2'-e]phosphepin[610304‑81‑9]C52H48P2FW 734.89

P

P

H

H

H3CCH3

CH3

CH3

H3CH3C

650870-100MG 100 mg

650870-500MG 500 mg

(S)-BINAPINE-rhodium complex

Rh+

BF4-

P

P

H

H

CH3

H3CH3C

CH3

H3CH3C

[(S)-BINAPINE(cyclooctadiene)rhodium(I)] tetrafluoroborateC60H60BF4P2RhFW 1032.78

659622-100MG 100 mg

659622-500MG 500 mg


ChiralQ

uest

Phosp

hine

LigandsandComplexes








(1R,1′R,2S,2′S)-DuanPhos

(1R,1′R,2S,2′S)-2,2′-Di-tert-butyl-2,3,2′,3′-tetrahydro-1H, 1′H-(1,1′)biisophosphindolyl[528814‑26‑8]C24H32P2FW 382.46

P

P

H

H CH3

CH3CH3

CH3

CH3CH3

657697-100MG 100 mg

657697-500MG 500 mg

(1R,1'R,2S,2'S)-DuanPhos-rhodium complex, 96%

((1R,1'R,2S,2'S)-DuanPhos (cyclooctadiene)rhodium(I)) tetrafluoroborateC32H44BF4P2RhFW 680.35

Rh+

P

PH

H

t-Bu

t-Bu

BF4

659673-100MG 100 mg

659673-500MG 500 mg

(S,S′,R,R′)-TangPhos

(1S,1S',2R,2R')-1,1'-Di-tert-butyl-(2,2')-diphospholane[470480‑32‑1]C16H32P2FW 286.37

PPt-Bu t-Bu

H

H

S: 22-24/25

650889-100MG 100 mg

650889-500MG 500 mg

(S,S',R,R')-TangPhos-rhodium complex

(S,S′,R,R')-TangPhos(cyclooctadiene)rhodium(I)] tetrafluoroborateC24H44BF4P2RhFW 584.26

Rh+

P

PH

H

t-Bu

t-Bu

BF4

659703-100MG 100 mg

659703-500MG 500 mg

(R)-C3-TunePhos

(R)-1,13-Bis(diphenylphosphino)-7,8-dihydro-6H-dibenzo[f,h][1,5]dioxonin[301847‑89‑2]C39H32O2P2FW 594.62

OO PPh2

PPh2

650862-100MG 100 mg

650862-500MG 500 mg

(R)-C3-TunePhos-ruthenium complex

OO

PH

PH

Ru2+

Cl

H3C

H3C

CH3

PhPh

ClPhPh

[Chloro(R)-C3-TunePhos)(p-cymene)ruthenium(II)] chlorideC49H46Cl2O2P2RuFW 900.81

659711-100MG 100 mg

659711-500MG 500 mg

(S)-Me-f-KetalPhos 8

1,1-Bis[(2S,3S,4S,5S)-2,5-dimethyl-3,4-O-isopropyl-idene-3,4-dihydroxyphospholanyl]ferroceneC28H40O4P2FeFW 558.41

Fe

P

P

CH3

H3C

CH3

H3C

OO

H3C CH3

O

O

CH3H3C

685674-100MG 100 mg

(S,S)-f-Binaphane 8

Fe

P

P

1,1′-Bis[(11bs)-3,5‑dihydro-4H-dinaphtho[2,1‑c:1′,2′-e]phosphenpin-4yl]ferrocene; 1,1′-Bis[(S)-4,5‑dihydro-3H-binaphtho[2,1‑c:1′,2′-e]phosphe-pino]ferrocene[544461‑38‑3]C54H40P2FeFW 806.69

685925-100MG 100 mg

Chiral Quest Ligands Kit I 8

Components(R)-Binaphane (Aldrich 650854) 100 mg(S,S)-f-Binaphane (Aldrich 685925) 100 mg(S)-Binapine (Aldrich 650870) 100 mg(1R,1′R,2S,2′S)-DuanPhos (Aldrich 657697) 100 mg(S)-Me-f-KetalPhos (Aldrich 685674) 100 mg(S,S′,R,R′)-TangPhos (Aldrich 650889) 100 mg(R)-C3-TunePhos (Aldrich 650862) 100 mg

687464-1KT 1 kit


Chira

lQuest

Phosp

hine

Ligandsand

Complexes
















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DSM MonoPhos™ Family

Feringa and co-workers have developed a diverse array of chiral,monodentate phosphoramidites based on the privileged BINOLplatform.1 The MonoPhos™ family has exhibited high levels ofenantiocontrol in synthetic transformations ranging from metal-catalyzedasymmetric 1,4‑additions of organometallic reagents to allylic alkylationsto desymmetrization of meso-cycloalkene oxides.2

Asymmetric 1,4‑Additionsof Organometallic ReagentsFeringa and co-workers showcases the high activity of the(S,R,R)-phosphoramidite ligand in copper-catalyzed 1,4‑additions oforganozinc reagents to cyclohexenones.1 Interestingly, the in situformed zinc species originating from the cyclohexenone is readilytrapped via a palladium-catalyzed allylation. It was followed by a formalannulation process through a palladium-catalyzed Wacker oxidation, andfinally by an aldol cyclization. The high (96%) enantioselectivity ofthis methodology is completely retained throughout this syntheticstrategy (Scheme 1).

Highly AsymmetricRhodium-Catalyzed HydrogenationFeringa has also gone to great lengths to develop structurally variedMonoPhos ligands in industrially useful transformations such asasymmetric hydrogenation.4 Impressively, the (S)-N-benzyl-N-methyl-MonoPhos derivative shown has been utilized in highly selectivehydrogenations of (E)-N-acylated dehydro-β-amino acid esters, affordingthe corresponding enantiopure β-amino acid derivatives (Scheme 2).4a

The authors found that this ligand, after being screened versus relatedchiral phosphoramidites, afforded the highest enantiocontrol inhydrogenations, albeit at slightly slower reaction times.

The Feringa research group has broadened the substrate scope of theasymmetric hydrogenation reaction by generating another chiral centeron the amine moiety of the phosphoramidite ligand. Amazingly, this fineligand tuning produces a very active and productive catalyst, which

efficiently hydrogenates a wide range of acetamido derivatives in lesstime than the corresponding Me-DuPhos analogs.4a Note that the chiral(S,R)-phosphoramidite ligand is the only ligand known to afford greaterthan 90% enantioselectivies for the substrate shown (Scheme 3).

Recently, Feringa's R&D group prepared additional structurally variedphosphoramidite ligands for rhodium-catalyzed asymmetrichydrogenations. The aptly named PipPhos and MorfPhos ligands containpiperidinyl and morpholinyl amine subunits, respectively, and areexamples of easily synthesized chiral ligands for highly effectiveenantioselective transformations. Under mild reaction conditionsincluding low H2 pressure, this catalyst system yields unprecedentedenantioselectivities for several substrates such as dimethyl itaconate andα-dehydroamino ester derivatives (Scheme 4).5

Asymmetric Regioselective Allylic AminationsHartwig and co-workers have succeeded in developing highly selectiveiridium catalysts with the (R,R,R)-phosphoramidite L.2g The allylicaminations of a wide variety of achiral allylic esters proceeded with totalconversion and superb regioselectivity in many cases. The reaction clearlyshows the power of this methodology; wherein, cinnamyl acetate wasconverted to the allylic benzyl amine in excellent yield and enantiopurity(Scheme 5). The authors mentioned that these valuable aminationreactions were mediated by air-stable Ir complexes at ambienttemperatures, which should lead to wide acceptance of this catalyst inbench-top organic synthesis.

References: (1)(a) Feringa, B. L. Acc. Chem. Res. 2000, 33, 346. (b) Minnaard, A. J. et al.Acc. Chem. Res. 2007, 40, 1267. (2) (a) Feringa, B. L. et al. Angew. Chem., Int. Ed. Engl.1997, 36, 2620. (b) Martina, S. L. X. et al. Tetrahedron Lett. 2005, 46, 7159. (c) Malda, H.et al. Org. Lett. 2001, 3, 1169. (d) Alexakis, A. et al. Chem. Commun. 2005, 2843.(e) Streiff, S. et al. Chem. Commun. 2005, 2957. (f) Bertozzi, F. et al. Org. Lett. 2000, 2,933. (g) Hartwig, J. F. et al. J. Am. Chem. Soc. 2002, 124, 15164. (3)(a) Pena, D. et al. J. Am.Chem. Soc. 2002, 124, 14552. (b) Van den Berg, M. et al. Adv. Synth. Catal. 2003, 345,308. (5) Bernsmann, H. et al. J. Org. Chem. 2005, 70, 943.

O

OP N

1. Cu(OTf)2 (2 mol %)ZnEt2, toluene, 30 C

88%, 96% ee

Ph

PhO

o

2. Pd(PPh3)4 (4 mol %)

OAc

O CuClPdCl2 (10 mol %)

DMF H2OO2

65%, 96% ee

O

O

4 mol% KOtBu

THF, rtO

H

56%, 96% ee

Scheme 1

O

OP N

Me

PhNHAc

CO2EtRh(cod)2BF4 (2 mol %)

cat.

H2 (10 bar), CH2Cl2, 4 h, rt

NHAc

CO2Et

99% ee

Scheme 2

O

OP N

H

Ph

NHAcCO2Me

Rh(cod)2BF4 (2 mol %)H2 (10 bar), CH2Cl2, 20 min, rt

NHAcCO2Me

94% ee

4 mol %

F F

Scheme 3

O

OP N

Rh(cod)2BF4 (2 mol %)

H2 (5 bar), CH2Cl2, rt

>99% ee

4 mol %

HN

O

O

OMe∗∗

HN

O

O

OMe

Scheme 4

O

OP N

[Ir(cod)Cl]2 (1 mol %), EtOH, rt

Ph

Ph

97:3 (3:4), 95%, 95% ee

(R,R,R)-L*, 2 mol %Ph OAc +

NH2Ph

NHBn

3

Ph NHBn

+

3 equiv

4

Scheme 5


DSM

MonoPhos™

Family


(S)-(+)-Benzyl(3,5‑dioxa-4‑phospha-cyclohepta[2,1‑a;3,4‑a′]dinaphthalen-4‑yl)methylamine, 97%

(+)-N-Benzyl-N-methyl-dinaphtho[2,1-d:1′,2′]dioxaphosphepin-4-amine, (11bS)[490023‑37‑5]C28H22NO2PFW 435.45

O

OP N

CH3

665355-100MG 100 mg

665355-500MG 500 mg

665355-2G 2 g

(S,R)-(+)-(3,5‑Dioxa-4‑phospha-cyclohepta[2,1‑a;3,4‑a′]di-naphthalen-4‑yl)-(1‑phenylethyl)amine, 96%

(+)-N-(1(R1-Phenylethyl)-dinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepin-4-amine,.(11b,S)[422509‑53‑3]C28H25NO2PFW 438.48

O

OP NH

CH3

665347-100MG 100 mg

665347-500MG 500 mg

(S,R,R)-(+)-(3,5‑Dioxa-4‑phospha-cyclohepta[2,1‑a;3,4‑a′]di-naphthalen-4‑yl)bis(1‑phenylethyl)amine, 97%

(+)-N,N-Bis[(1R)-1-phenylethyl]-dinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepin-4-amine, (11bS)[415918‑91‑1]C36H30NO2PFW 539.60 O

PO

NCH3

CH3

665363-100MG 100 mg

665363-500MG 500 mg

665363-2G 2 g

(S,S,S)-(+)-(3,5‑Dioxa-4‑phospha-cyclohepta[2,1‑a;3,4‑a']di-naphthalen-4‑yl)bis(1‑phenylethyl)amine, 97%

(+)-N,N-Bis[(1S)-1-phenylethyl]- dinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepin- 4-amine, (11bR)[380230‑02‑4]C36H30NO2PFW 539.60

O

OP N

CH3

CH3

Ph

Ph

665290-100MG 100 mg

665290-500MG 500 mg

665290-2G 2 g

(R)-(−)-(3,5‑Dioxa-4‑phosphacyclohepta[2,1‑a;3,4‑a′]di-naph-thalen-4‑yl)dimethylamine, 97%

(R)-Monophos[157488‑65‑8]C22H20NO2PFW 361.37 O

PO

NCH3

CH3

668206-100MG 100 mg

668206-250MG 250 mg

668206-1G 1 g

668206-5G 5 g

(S)-(+)-(3,5‑Dioxa-4‑phosphacyclohepta[2,1‑a;3,4- a′]di-naph-thalen-4‑yl)dimethylamine, 97%

(S)-Monophos[185449‑80‑3]C22H18NO2PFW 359.36 O

PO

NCH3

CH3

668192-100MG 100 mg

668192-250MG 250 mg

668192-1G 1 g

668192-5G 5 g

(11bR)-2,6-Bis(diphenylphosphino)-N,N-dimethyldi-naphtho[2,1-d:1′,2′-f]-1,3,2-dioxaphosphepin-4-amine

8

[913617‑04‑6]C46H36NO2P3FW 727.70

O

OP N

CH3

CH3

P

P

683248-100MG 100 mg

683248-500MG 500 mg


DSM

MonoPhos™

Family























(S)-(+)-(3,5‑Dioxa-4‑phosphacyclohepta[2,1‑a;3,4‑a′]dinaph-thalen-4‑yl)morpholine, 97%

C24H20NO3PFW 401.39

O

OP N O

665487-100MG 100 mg

665487-500MG 500 mg

665487-2G 2 g

(S)-(+)-(3,5‑Dioxa-4‑phospha-cyclohepta[2,1‑a;3,4‑a′]dinaph-thalen-4‑yl)piperidine, 97%

(S)-(+)-4-Dinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphos-phepin-4-yl-piperidineC25H22NO2PFW 399.42

O

OP N

665479-100MG 100 mg

665479-500MG 500 mg

665479-2G 2 g

(11bS)-N,N-dimethyl-8,9,10,11,12,13,14,15-octahydro-dinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepin-4-amine

8

[389130‑06‑7]C22H26NO2PFW 367.42 O

OP N

CH3

CH3

685569-100MG 100 mg

685569-500MG 500 mg

(3aR,8aR)-(−)-(2,2‑Dimethyl-4,4,8,8‑tetraphenyl-tetrahydro-[1,3]dioxolo[4,5‑e][1,3,2]dioxaphosphepin-6‑yl)dimethyl-amine, 96%

[213843‑90‑4]C33H34NO4PFW 539.60

OP

OO

O

H3C

H3CN

CH3

CH3

665460-100MG 100 mg

665460-500MG 500 mg

sigma-aldrich.com

8 Chiral Vicinal Diamines for Asymmetric Synthesis

Chiral vicinal diamines are of tremendous interest to the synthetic chemist as they are found in many chiral catalysts and pharmaceuticals. Currently, there is no unified approach to making these chiral vicinal diamines, and they are often challenging to synthesize, especially if unsymmetrically substituted. Jik Chin and co-workers have recently reported some preliminary theoretical and experimental studies for converting a parent diamine (1) into other chiral vicinal diamines.1 These diamines can be used as ligands for chiral catalysts, or they can be further elaborated to produce chiral heterocyclic rings and β-lactams via ring closure.

References: (1)(a) Chin, J. et al. J. Am. Chem. Soc. 2003, 125, 15276. (b) Kim, H.-J. et al. J. Am. Chem. Soc. 2005, 127, 16370. (c) Kim, H.-J. et al. J. Am. Chem. Soc. 2005, 127, 16776.

NH2

NH2

OH

OH

685879(S,S)-1

NH2

NH2N

N

CH3

H3C

CH3

CH3

• 4 HCl

685186

NH2

NH2

Cl

Cl• 2 HCl

684058

NH2

NH2O2N

NO2

• 2 HCl

684031

NH2

NH2H3CO

OCH3

OCH3

H3CO

OCH3

H3CO

• 2 HCl

684023

NH2

NH2

• 2 HCl

684147

NH2

NH2F

F

• 2 HCl

684139

NH2

NH2H3CO

OCH3

• 2 HCl

684120

Other 8 Chiral Vicinal Diamines

NH2

NH2

OH

OH

1) R1CHO

2) R2CHON

N

OH

OH

R1

R2

[3,3]

N

N

OH

OH

R1

R2

H2O

H2N

H2N R1

R2

1

NH2

NH2

OH

OH

685860(R,R)-1

NH2

H2NH3C

CH3

CH3H3C

CH3

H3C

684104


DSM

MonoPhos™

Family























Reetz Ligands

In 1998, Reetz et al. reported the synthesis of a new generation of ligandfor enantioselective, catalyzed hydrogenation. Based on BINOL-deriveddiphosphonite molecules, these ligands showed good enantioselectivitiesfor the asymmetric hydrogenation of terminal alkenes, ketones, andβ-keto esters,1,2 and the asymmetric conjugate addition of arylboronicacid derivatives to α,β-unsaturated carbonyls.3

Enantioselective Hydrogenation of OlefinsReetz et al. reported the hydrogenation of two different olefins withRh(cod)BF4 and R,R-Reetz F-Diphosphonite. Outstanding yields andselectivity were reported (Scheme 1).4

Used with a RuCl2(p-cymene)2 complex, the R,R-Reetz X-Diphosphoniteconverts a variety of ketones into secondary alcohols with yields and ee'sup to 100% and 98%, respectively (Scheme 2).1

References: (1) Reetz, M. T. et al. J. Am. Chem. Soc. 2006, 128, 1044. (2) Reetz, M. T. et al.Adv. Synth. Catal. 2006, 348, 1157. (3) Reetz, M. T. et al. Org. Lett. 2001, 3, 4083.(4) Reetz, M. T. et al. Chem. Commun. 1998, 2077.

Fe OPO

OP

O

MeO2CCO2Me

MeO2CCO2Me

R,R-Reetz F-diphosphonite

Rh(cod)BF4, H2

R,R-Reetz F-diphosphonite :

MeO2C NH

MeO2C NH

R,R-Reetz F-diphosphonite

Rh(cod)BF4, H2

Me

O

100%, >99.5% ee

100%, >99% ee

Me

O

Scheme 1

O

O OP

O OP

H3C CH3

R

O

CH3 R1 CH3

OH[RuCl2(p-cymene)]2 (0.5 mol%)

iPrOH, base (10 mol%)

(1.25 mol%)

R Yield (%) ee (%)Ph 93 98m-MeOPh 91 93m-BrPh 100 96p-ClPh 96 96p-BrPh 98 95

Scheme 2

(11bS,11′bS)-4,4′-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis-dinaphtho[2,1-d:1′,2′-f][1,3,2]dioxaphosphepin

8

S,S-Reetz X-Diphosphonite[349114‑57‑4]C55H36O5P2FW 838.82

O

O

O

OP

P

OCH3

CH3

682869-100MG 100 mg

682869-500MG 500 mg

(11bR,11′bR)-4,4′-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis-dinaphtho[2,1-d:1′, 2′-f][1,3,2]dioxaphosphepin

8

R, R-Reetz X-Diphosphonite[349114‑63‑2]C55H36O5P2FW 838.82

O

O

O

OP

P

OCH3

CH3

682977-100MG 100 mg

682977-500MG 500 mg

1,1′Bis[(11bS)-dinaphtho[2,1-d:1′, 2′-f][1,3,2]dioxaphosphepin-4-yl]ferrocene

8

Fe

O

OP

O

OP

S,S-Reetz F-Diphosphonite[260395‑56‑0]C50H32FeO4P2FW 814.58

682942-100MG 100 mg

682942-500MG 500 mg

1,1′Bis[(11bR)-dinaphtho[2,1-d:1′, 2′-f][1,3,2]dioxaphosphepin-4-yl]ferrocene

8

Fe

O

OP

O

OP

R, R-Reetz F-Diphosphonite[217175‑10‑5]C50H32FeO4P2FW 814.58

LR: 40 S: 23-24/25-36/37

682950-100MG 100 mg


Reetz

Ligands









(11bS, 11′bS)-4,4′-(Oxydi-2,1-phenylene)bis-dinaph-tho[2,1-d: 1′, 2′-f][1,3,2]dioxaphosphepin

8

S, S-Reetz D-Diphosphonite[898830‑89‑2]C52H32O5PFW 767.78

O

O

O

OP

P

O

JLR: 11-48/20-63-65-67 S: 36/37-46-62

682985-100MG 100 mg

682985-500MG 500 mg

(11bR, 11′bR)-4,4′-(Oxydi-2,1-phenylene)bis-dinaph-tho[2,1-d:, 1′, 2′-f][1,3,2]dioxaphosphepin

8

R, R-Reetz D-Diphosphonite[391860‑55‑2]C52H32O5PFW 767.78

O

O

O

OP

P

O

LR: 48/20-63-65 S: 36/37-45-62

682993-100MG 100 mg

682993-500MG 500 mg

Accelerate Chiral Separationwith ChiroSolv® Kits

Sigma-Aldrich® is pleased to partner with ChiroSolve, Inc. to offer a series of ready-to-use, disposable kits for chiral resolution of both solid and liquid racemates. These kits allow scientists to quickly screen calibrated quantities of resolving agents and solvents against a racemate to fi nd the optimum combination, as well as optimize reaction conditions in order to separate a racemic mixture into its constituent enantiomers. The kits’ high throughput format allows scientists to identify the optimum resolution process within 24 hours that might otherwise take over 2 months.

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Prod. No. Prod. Name/Description681431 ChiroSolv Resolving Kit, Acid Series 1681423 ChiroSolv Resolving Kit, Acid Series 2681415 ChiroSolv Resolving Kit, Acid Series 3699217 ChiroSolv Resolving Kit, Acid Series 4700363 ChiroSolv Resolving Kit, Complete Acid Series681407 ChiroSolv Resolving Kit, Base Series 1681393 ChiroSolv Resolving Kit, Base Series 2681377 ChiroSolv Resolving Kit, Base Series 3699241 ChiroSolv Resolving Kit, Base Series 4700371 ChiroSolv Resolving Kit, Complete Base Series

Prod. No. Prod. Name/Description698881 ChiroSolv Resolving Kit, Acid Series 1699527 ChiroSolv Resolving Kit, Acid Series 2698873 ChiroSolv Resolving Kit, Acid Series 3699225 ChiroSolv Resolving Kit, Acid Series 4700398 ChiroSolv Resolving Kit, Complete Acid Series699233 ChiroSolv Resolving Kit, Base Series 1698938 ChiroSolv Resolving Kit, Base Series 2698946 ChiroSolv Resolving Kit, Base Series 3698954 ChiroSolv Resolving Kit, Base Series 4700401 ChiroSolv Resolving Kit, Complete Base Series

Product Information for Solid RacematesProduct Information for Liquid Racemates


Reetz

Ligands





http://www.sigma-aldrich.com/chirosolv























BINOL and Derivatives

BINOL and its derivatives are one of the mostly widely used classes ofligands in asymmetric synthesis; being utilized in a broad array ofreactions including: Diels–Alder, carbonyl addition and reductions,Michael additions, as well as many others. While tremendous success hasbeen obtained with the BINOL platform, other C2-symmetric diol ligandshave attracted considerable attention. Among these are the vaultedbiaryl ligands developed by Wulff and co-workers. Both vaulted3,3'-biphenanthrol (VAPOL) and vaulted 2,2'-binaphthol (VANOL) haveproven to be excellent ligands in catalytic asymmetric Diels–Alder, iminealdol, and aziridination reactions (Figure 1).1 Recently the phosphoricacid derivative of VAPOL was shown to be effective as a chiral Brønstedacid catalyst. In many of the examples illustrated herein, the vaultedbiaryls give both higher yields and higher inductions than the samereactions using a BINOL ligand.

Asymmetric Diels–Alder ReactionVery early on, a catalyst generated from Et2AlCl and VAPOL was shownto be an effective catalyst for the asymmetric Diels-Alder reaction.2 Asshown in Scheme 1, the cycloaddition of acrolein with cyclopentadienein the presence of the VAPOL-derived catalyst gave high conversions andexcellent stereoselectivities for the exo isomer in very high optical purity.Analogous reactions with the BINOL-derived catalyst provided thecycloadduct in high yield, but in very low enantiomeric excess (13–41%).

Asymmetric Aziridination ReactionAziridines are important building blocks in organic synthesis becausethey allow for convenient access to amines, amino alcohols, diamines,and other useful nitrogen-containing molecules. Most contemporarymethods of chiral aziridine preparation have relied on the chiral pool.Recently, the Wulff group has developed a robust catalytic asymmetricaziridination reaction providing optically active aziridines in high yieldsand selectivities. The reaction relies on the addition of commerciallyavailable ethyl diazoacetate (EDA) to benzhydryl imines in the presenceof arylborate catalysts prepared from vaulted aryl ligands and B(OPh)3.3

The aziridination reaction exhibits excellent selectivities for the cis isomer,and high enantiomeric excesses are obtained. The resultant benzyhydryl-protected aziridines undergo a variety of reactions, including:deprotection, reductive ring opening, or alkylation reactions (Scheme 2,Table 1). The asymmetric synthesis of leukointegrin LFA-1 antagonistBIRT-377 utilized an aziridination/alkylation methodology to provide thehydantoin target in excellent overall yield.

The highly expeditious synthesis of the antibacterial agent(–)-chloramphenicol utilized the asymmetric aziridination reaction,followed by a nucleophilic ring opening of the aziridine with dichloro-acetic acid with a subsequent acyl group migration (Scheme 3, Table 2).Both VANOL and VAPOL gave higher yields and stereoselectivities thanthe BINOL-derived catalyst.

Asymmetric Aldol ReactionAsymmetric imine aldol reactions are also catalyzed by vaultedbiaryl-derived catalysts, providing an important method for the synthesisof chiral β-amino esters. The addition of silyl ketene acetals to aryl iminesin the presence of either Zr-VANOL or Zr-VAPOL catalysts proceeds withhigh asymmetric induction and in excellent yield (Scheme 4, Table 3).Significantly, both catalysts exhibit substantially higher levels of inductionover the analogous BINOL-derived catalyst.4

Chiral Brønsted AcidAntilla and co-workers demonstrated VAPOL hydrogenphosphate to be auseful chiral Brønsted acid catalyst in the addition of sulfonamides toBoc-activated aryl imines (Scheme 5).5 The resultant N,N-aminalproducts were prepared in high yields with impressive enantiopurities.The identical reaction with a BINOL-derived Brønsted acid catalyst gavean excellent yield (95%), but a dismal level of asymmetric induction(<5% ee) was obtained. A variety of sulfonamides and aryl imines areactive in the imine amidation reaction, and the resultant protectedaminals are shelf-stable compounds.

References: (1)(a) Bao, J. et al. J. Am. Chem. Soc. 1996, 118, 3392. (b) Zhang, Y. et al. Org.Lett. 2003, 5, 1813. (c) Yu. S. et al. Org. Lett. 2005, 7, 367. (2)(a) Bao, J.; Wulff, W. D. J.Am. Chem. Soc. 1993, 115, 3814. (b) Bao, J.; Wulff, W. D. Tetrahedron Lett. 1995, 36,3321. (c) Heller, D. P. et al. J. Am. Chem. Soc. 1997, 119, 10551. (3)(a) Antilla, J. C.; Wulff,W. D. J. Am. Chem. Soc. 1991, 121, 5099. (b) Antilla, J. C.; Wulff, W. D. Angew. Chem., Int.Ed. 2000, 39, 4518. (c) Loncaric, C.; Wulff, W. D. Org. Lett. 2001, 3, 3675. (d) Patwardhan,A. P. et al. Angew. Chem., Int. Ed. 2005, 44, 6169. (e) Patwardhan, A. P. et al. Org. Lett.2005, 7, 2201. (4) Xue, S. et al. Angew. Chem., Int. Ed. 2001, 40, 2271. (5) Rowland, G. B.et al. J. Am. Chem. Soc. 2005, 127, 15696.

PhPh O

OP

O

OHPhPh OH

OHPhPh OH

OH

(S)-VANOL (S)-VAPOL (S)-VAPOL Hydrogenphosphate

OHOH

(S)-BINOL

Figure 1

CHO

CH3

CH3

CHO

Et2AlCl/(S)-VAPOL catalyst (1:1) (0.5 mol %), CH2Cl2, ca. −80 °C 97% (NMR), 97.7% ee (GC)

(xs)

Scheme 1


BIN

OLand

Derivatives


NCHPh2

CO2EtPhCO2Et

NH2 NH

Ph CO2Et

Pd black

HCO2H, MeOH, rt

1) O3, CH2Cl2, −78 °C

2) NaBH4, MeOH

NCHPh2

(EDA)+

Ligand/B(OPh)3 catalyst

X = HX = H

X

X

NCHPh2

CO2Et

Br

CH3

NN

O

O

H3C

BrCH3

BIRT−377

LDA, DME/Et2O, −78 °C; then MeI, −78 °C to rt

86%

60%D-phenylalanine ethyl ester, 80%

EtON2

O

X = 4-Br

Scheme 2

EntryLigand, Loading X

Time (h)

Yield (%) cis:trans ee (%)

1(S)-BINOL, 10 mol %

H 3 61 17:1 20

2(S)-VANOL, 10 mol %

H 0.5 85 >50:1 96

3(S)-VAPOL, 2 mol %

H 48 77 >50:1 95

4(S)-VAPOL, 1 mol %

4-Br 20 87 >50:194 (>99% ee

recryst.)

Table 1

NO2

HO

OH

NHCl2HC

O

NCHPh2

EtO2C

NO2

NCHPh2

EDA

+O2N

Ligand/B(OPh)3 catalyst (10 mol %)

Cl2HCCO2H

NO2

EtO2COH

NHCl2HC

O

80%

NaBH4

1,2-C2H4Cl2, Δ

MeOH, 0 °C

74%

(−)-chloramphenicol

toluene, 0 to 22 °C

Scheme 3

Entry LigandTime (h)

Yield (%) cis:trans ee (%)

1 (R)-BINOL 26 72 19:1 22

2 (S)-VANOL 26 77 >50:1 91a

3 (R)-VAPOL 21 80 30:1 96 (99% ee recryst.)a Product is the enantiomer of the aziridine shown.

Table 2

Ph

N

100%, 86% ee

HO

MeO OTMS

Ph OMe

NH2 OLigand/Zr(Oi-Pr)4 catalyst (2.2:1), (2 mol %)

toluene, 40 °C

+

Scheme 4

Entry LigandLoading (mol %) Solvent

Temp (°C)

Time (h)

Yield (%)

ee (%)

1 (R)-BINOL 20 CH2Cl2 25 4 100 28

2 (S)-VAPOL 20 Toluene 25 15 94 89

3 (S)-VAPOL 2 Toluene 40 6 100 86

Table 3

N HN

N(H)Ts*

TsNH2+(S)-VAPOL Hydrogenphosphate (5 mol %)

Et2O, rt, 1 h

Boc Boc

95%, 94% ee

Scheme 5


BIN

OLand

Deriv

ativ

es


(R)-(+)-1,1′-Bi(2‑naphthol), 99%

(R)-BINOL; (+)-2,2′-Dihydroxy-1,1′-dinaphthyl; (R)-(+)-1,1′-Binaphthalene-2,2′-diol[18531‑94‑7]C20H14O2

FW 286.32

OHOH

KR: 25-36 S: 26-45 RTECS # DU3106100

246948-1G 1 g

246948-5G 5 g

246948-10G 10 g

(S)-(−)-1,1′-Bi(2‑naphthol), 99%

(S)-BINOL; (−)-2,2′-Dihydroxy-1,1′-dinaphthyl; (S)-(−)-1,1′-Binaphthalene-2,2′-diol[18531‑99‑2]C20H14O2

FW 286.32

OHOH

KR: 25-36 S: 26-45 RTECS # DU3106100

246956-1G 1 g

246956-5G 5 g

246956-25G 25 g

(R)-(−)-1,1′-Bi-2‑naphthol bis(trifluoromethanesulfonate),97%

(R)-1,1′-Binaphthalene-2,2′-diyl bis(trifluoromethane-sulfonate); (R)-1,1'-Bi(2-naphthol) bis(trifluorometh-anesulfonate)[126613‑06‑7]C22H12F6O6S2FW 550.45

OS

CF3

OS

CF3

O O

O O

MR: 34 S: 26-36/37/39-45

440590-250MG 250 mg

440590-1G 1 g

440590-5G 5 g

(S)-(+)-1,1′-Bi-2‑naphthol bis(trifluoromethanesulfonate),97%

(S)-1,1'-Bi(2-naphthol) bis(trifluoromethanesulfonate);(S)-1,1′-Binaphthalene-2,2′-diyl bis(trifluoromethane-sulfonate)[128544‑05‑8]C22H12F6O6S2FW 550.45

OS

CF3

OS

CF3

O O

O O

MR: 34 S: 26-36/37/39-45

431893-250MG 250 mg

431893-1G 1 g

431893-5G 5 g

(R)-(−)-1,1'-Bi-2‑naphthyl dimethanesulfonate, 97%

[871231‑48‑0]C22H18O6S2FW 442.50 O

OS

SOO

O CH3

O CH3

LR: 36 S: 26

631795-250MG 250 mg

(S)-(+)-1,1'-Bi-2‑naphthyl dimethanesulfonate, 97%

[871231‑47‑9]C22H18O6S2FW 442.50 O

OS

SOO

O CH3

O CH3

LR: 36 S: 26

631787-250MG 250 mg

(R)-(−)-1,1'- Bi-2‑naphthyl ditosylate, 98%

[137568‑37‑7]C34H26O6S2FW 594.70 O

OS

S CH3

CH3O O

O O

LR: 36/37/38 S: 26-36

596914-5G 5 g

596914-25G 25 g

(S)-(+)-1,1'-Bi-2‑naphthyl ditosylate, 97%

[128544‑06‑9]C34H26O6S2FW 594.70 O

OS

S CH3

CH3O O

O O

LR: 36/37/38 S: 26-36

597252-5G 5 g

597252-25G 25 g


BIN

OLand

Derivatives




















(R)-(+)-3,3′-Bis(3,5‑bis(trifluoromethyl)phenyl)-1,1′-bi-2‑naph-thol, 95%

[756491‑54‑0]C36H18F12O2

FW 710.51

CF3

CF3

CF3

CF3

OHOH

LR: 36/37/38 S: 26

674591-100MG 100 mg

(S)-(–)-3-3′-Bis(3,5-bis(trifluoromethyl)phenyl)-1,1′-bi-2-naphthol, 95%

8

(1S)-3,3′-Bis[3,5-bis(trifluoromethyl)phenyl]1,1′-bi-naphthalene-2,2′-diol[849939‑13‑5]C36H18F12O2

FW 710.51

CF3

CF3

CF3

CF3

OHOH

LR: 36 S: 26

681539-100MG 100 mg

(R)-(−)-3,3′-Bis(3,5‑dimethylphenyl)-5,5′,6,6′,7,7′,8,8′-octa-hydro-1,1′-bi-2‑naphthol, 97%

(R)-3,3′-Bis(3,5-dimethylphenyl)-5,6,7,8,5,′,6′,7′,8′-octahydro-[1,1′]binaphthalenyl-2, 2′-diolC36H38O2

FW 502.69OHOH

CH3

CH3

CH3

CH3

669180-100MG 100 mg

(S)-(+)-3,3′-Bis-(3,5‑dimethylphenyl)-5,5′,6,6′,7,7′,8,8′-octa-hydro-1,1′-bi-2‑naphthol, 97%

(S)-3,3′-bis-(3,5-dimethylphenyl)-5,6,7,8,5′,6′,7′,8′-octahydro-[1,1′]binaphthalenyl-2,2′-diolC36H38O2

FW 502.69OHOH

CH3

CH3

CH3

CH3

669172-100MG 100 mg

(R)-(+)-2,2'-Bis(methoxymethoxy)-1,1'-binaphthalene, 97%

[173831‑50‑0]C24H22O4

FW 374.43 OO O

CH3

OCH3

LQR: 41-50/53 S: 25-26-36/39-60-61

631582-250MG 250 mg

(S)-(−)-2,2'-Bis(methoxymethoxy)-1,1′-binaphthalene, 97%

[142128‑92‑5]C24H22O4

FW 374.43 OO O

CH3

OCH3

LQR: 41-50/53 S: 25-26-36/39-60-61

631574-250MG 250 mg

(R)-3,3′-Bis(triphenylsilyl)-1,1′-bi-2‑naphthol, 96%

(R)-3,3′-Bis(triphenylsilyl)-1,1′-binaphthalene-2,2′-diol[111822‑69‑6]C56H42O2Si2FW 803.10 OH

OH

Si

Si

Ph

PhPh

Ph

PhPh

674737-100MG 100 mg

(S)-(–)-3,3′-Bis(triphenylsilyl)-1,1′-bi-2‑naphthol, 96%

C56H42O2Si2FW 803.10

OH

OH

Si

Si

Ph

PhPh

Ph

PhPh

680206-100MG 100 mg

(R)-(+)-3,3′-Dibromo-1,1′-bi-2‑naphthol, 97%

[111795‑43‑8]C20H12Br2O2

FW 444.12OHOH

Br

Br

595721-250MG 250 mg

595721-1G 1 g


BIN

OLand

Deriv

ativ

es












(R)-(−)-6,6′-Dibromo-1,1′-bi-2‑naphthol, 98%

[65283‑60‑5]C20H12Br2O2

FW 444.12OH

Br

Br

OH

LR: 36/37/38 S: 26-36

482617-500MG 500 mg

(S)-(+)-6,6′-Dibromo-1,1′-bi-2‑naphthol, 98%

[80655‑81‑8]C20H12Br2O2

FW 444.12OH

Br

Br

OH

LR: 36/37/38 S: 26-36

482625-250MG 250 mg

482625-500MG 500 mg

(S)-(−)-3,3′-Dibromo-1,1′-bi-2‑naphthol, 96%

[119707‑74‑3]C20H12Br2O2

FW 444.12OHOH

Br

Br

595837-250MG 250 mg

595837-1G 1 g

(R)-(+)-6,6'-Dibromo-2,2′-bis(methoxymethoxy)-1,1′-binaph-thalene, 97%

[179866‑74‑1]C24H20Br2O4

FW 532.22 OO

Br

Br

OCH3

OCH3

LR: 41 S: 25-26-36/39

631604-250MG 250 mg

(S)-(−)-6,6'-Dibromo-2,2′-bis(methoxymethoxy)-1,1′-binaph-thalene, 97%

[211560‑97‑3]C24H20Br2O4

FW 532.22 OO

Br

Br

OCH3

OCH3

LR: 41 S: 25-26-36/39

631590-250MG 250 mg

(R)-(+)-3,3′-Dibromo-5,5′,6,6′,7,7′,8,8′-octahydro-1,1′-bi-2,2′-naphthalenediol, 97%

[65355‑08‑0]C20H20Br2O2

FW 452.18

Br

OH

Br

OH

LR: 36/37/38 S: 26-36

540587-100MG 100 mg

540587-1G 1 g

(S)-(−)-3,3′-Dibromo-5,5′,6,6′,7,7′,8,8′-octahydro-1,1′-bi-2,2′-naphthalenediol, 97%

[765278‑73‑7]C20H20Br2O2

FW 452.18

Br

OH

Br

OH

LR: 36/37/38 S: 26-36

540595-100MG 100 mg

540595-1G 1 g

(R)-(+)-2,2′-Dimethoxy-1,1′-binaphthalene, 97%

(R)-(+)-2,2′-Dimethoxy-1,1′-binaphthyl; (R)-1,1′-Bi-2-naphthyl dimethyl ether[35294‑28‑1]C22H18O2

FW 314.38

OCH3

OCH3

LR: 41 S: 26-36

595403-250MG 250 mg

(S)-(−)-2,2'-Dimethoxy-1,1'-binaphthalene, 97%

(S)-(−)-2,2'-Dimethoxy-1,1'-binaphthyl; (S)-1,1′-Bi-2-naphthyl dimethyl ether[75640‑87‑8]C22H18O2

FW 314.38

OCH3

OCH3

LR: 41 S: 26-36

595519-250MG 250 mg

(R)-(+)-Dimethyl-2,2′-dihydroxy-1,1′-binaphthalene-3,3′-dicarboxylate, 98%

[18531‑91‑4]C24H18O6

FW 402.40 OCH3

OCH3

O

O

OHOH

LR: 36/37/38 S: 26-36

579343-2G 2 g


BIN

OLand

Derivatives
















(S)-(−)-Dimethyl-2,2′-dihydroxy-1,1′-binaphthalene-3,3′-dicarboxylate

[69678‑00‑8]C24H18O6

FW 402.40 OCH3

OCH3

O

O

OHOH

LR: 36/37/38 S: 26-36

98%

579971-2G 2 g

(R)-(+)-5,5′,6,6′,7,7′,8,8′-Octahydro-1,1′-2‑naphthol

[65355‑14‑8]C20H22O2

FW 294.39 OHOH

LR: 36/37/38 S: 26-36

97%

540560-1G 1 g

95%

569917-1G 1 g

569917-5G 5 g

(S)-(−)-5,5′,6,6′,7,7′,8,8′-Octahydro-1,1′−bi-2‑naphthol, 97%

[65355‑00‑2]C20H22O2

FW 294.39 OHOH

LR: 36/37/38 S: 26

540579-100MG 100 mg

540579-1G 1 g

(R)-VANOL, 97%

(R)-3,3'-Diphenyl-2,2'-bi-1-naphthalol; (R)-3,3'-Diphenyl-2,2'-bi-1-naphthol[147702‑13‑4]C32H22O2

FW 438.52 OHPhPh

OH

LR: 37/38-41 S: 26-39

675156-250MG 250 mg

(S)-VANOL, 97%

(S)-3,3′-Diphenyl-2,2′-bi(1-naphthalol); (S)-3,3′-Diphenyl-2,2′-bi-(1-naphthol)[147702‑14‑5]C32H22O2

FW 438.52 OHPhPh

OH

LR: 37/38-41 S: 26-36/37/39

676098-250MG 250 mg

(R)-VAPOL, 97%

(R)-2,2'-Diphenyl-3,3'-(4-biphenanthrol); (R)-2,2'-Diphenyl-3,3'-(4-biphenanthrol)[147702‑16‑7]C40H26O2

FW 538.63 OHPhPh

OH

LR: 37/38-40-41 S: 26-36/37/39

675210-100MG 100 mg

675210-250MG 250 mg

675210-500MG 500 mg

(S)-VAPOL, 97%

(S)-2,2'-Diphenyl-(4-biphenanthrol); (S)-2,2'-Diphenyl-(4-biphenanthrol)[147702‑15‑6]C40H26O2

FW 538.63 OHPhPh

OH

LR: 37/38-40-41 S: 26-36/37/39

675334-100MG 100 mg

675334-250MG 250 mg

675334-500MG 500 mg

BINOL Ligands Kit I

Components(S)-(−)-1,1′-Bi(2‑naphthol) (Aldrich 246956) 1g(S)-(+)-6,6′-Dibromo-1,1′-bi-2‑naphthol (Aldrich 482625) 250mg(S)-(−)-5,5′,6,6′,7,7′,8,8′-Octahydro-1,1′−bi-2‑naphthol (Aldrich 540579) 100mg(S)-(−)-3,3′-Dibromo-5,5′,6,6′,7,7′,8,8′-octahydro-1,1′-bi-2,2′-naphthalenediol (Al-drich 540595) 100mg(S)-(−)-2,2'-Dimethoxy-1,1'-binaphthalene (Aldrich 595519) 250mg(S)-(−)-3,3′-Dibromo-1,1′-bi-2‑naphthol (Aldrich 595837) 250mg

KR: 25-37/38-41 S: 26-39-45

669113-1KT 1 kit


BIN

OLand

Deriv

ativ

es

















TADDOL

The chiral auxiliaries TADDOLs (α,α,α,α-tetraaryl-1,3-dioxolane-4,5-dimethanols) developed by Seebach's group have found numerousapplications in asymmetric synthesis ranging from utilization asstoichiometric chiral reagents or in Lewis acid mediated reactions, toroles in catalytic hydrogenation and stereoregular metathesispolymerization.1

Nucleophilic AdditionThe principal field of application of TADDOLs to date is in Ti-catalyzed,enantioselective reactions. Nucleophilic additions of organometalliccompounds to aldehydes are depicted in Scheme 1. The preparation ofthe Ti-TADDOLate complex used in such transformations is critical withrespect to reproducibility.1

Enantioselective transfers of allyl groups to aldehydes are most successfulusing Duthaler's CpTi-TADDOLate complexes 449520 or 449539(Scheme 2).2

Enantioselective TransesterificationSeveral examples of enantioselective transesterifications were reportedfor ring openings of lactones and cyclic anhydrides using Ti-TADDOLateof 393762 (Scheme 3). The observed selectivity in this desymmetrizationstep is largely independent of structure. The half esters obtained arereadily converted into the corresponding γ-lactones.3

It is worth mentioning that TADDOL 395242 bearing 1‑naphthyl groupsinfrequently differs in its reactivity from the other TADDOLs (a dramaticloss in enantioselectivity is observed in Ti-TADDOLate catalyzed additionreactions described previously). This change in reactivity could beexplained with the higher steric hindrance around the chiral pocket ofthe active site.4

Enantioselective ProtonationNevertheless, surprisingly stereoselective examples using TADDOL395242 were found in enantioselective protonation reactions(Scheme 4),5 the first example of a catalytic enantioselective fluorinationreaction reported by Hintermann and Togni used the Cl2Ti-complex of395242 (Scheme 5)6 as well as the recent example reported by Rawalusing 395242 as a Brønsted acid organocatalyst in a highlyenantioselective hetero-Diels-Alder reaction (Scheme 6).7

References: (1) Seebach, D.; Beck, A. K.; Heckel, A. Angew. Chem., Int. Ed. 2001, 40,92‑138. (2) Duthaler, R. O.; Hafner, A. Chem. Rev. 1992, 92, 807‑832. (3)(a) Seebach, D.;Jaeschke, G.; Wang, Y. M. Angew. Chem., Int. Ed. Engl. 1995, 34, 2395‑2396. (b) Jaeschke,G.; Seebach, D. J. Org. Chem. 1998, 63, 1190‑1197. (4)(a) Seebach, D.; Dahinden, R.;Marti, R. E.; Beck, A. K.; Plattner, D. A.; Kühnle, F. N. M. J. Org. Chem. 1995, 60,1788‑1799. (b) Seebach, D.; Dahinden, R.; Marti, R. E.; Beck, A. K.; Plattner, D. A.; Kühnle,F. N. M. J. Org. Chem. 1995, 60, 5364. (5) Cuenca, A.; Medio-Simón, M.; Asensio Aguilar,G.; Weibel, D.; Beck, A. K.; Seebach, D. Helv. Chim. Acta 2000, 83, 3153‑3162.(6) Hintermann, L.; Togni, A. Angew. Chem., Int. Ed. 2000, 39, 4359‑4362. (7) Huang, Y.;Unni, A. K.; Thadani, A. N.; Rawal, V. H. Nature 2003, 424, 146.

OHHO

CH3H3C

OHCH3

99% ee98% ee

H3CCH3

OH

98% ee

OH

O2N

96% ee

TMSCH3

OH

96% ee

O

TBSO HOH

CH3

CH2

99% de

OHCH3

O

H

(i-PrO)2Ti-TADDOLate (0.05-0.2 eq)

Et2Zn (1-2 eq.)Ti(Oi-Pr)4 (1-2 eq.)

-75° to 0°C

O

O

RR O

TiO

Ar Ar

Ar Ar

Oi-Pr

Oi-Pr

H

H

98% ee

Scheme 1

O

O

H3CH3C O

TiO

Ph Ph

Ph Ph

Cl

H

H

M R1

R2-CHOR2

OH

R1CH2

M = Li, MgCl, MgBr

OH

CH3

CH2

98% ee, 98% de

C9H19

OH

CH3

CH2

98% ee, >98% de

OH

CH2

98% ee, >98% de

H2C

OH OH

H2C

OH OH

85%, 94% de 75%, 94% de

O

NOH

TMSCH2

94% ee, 98% de

OTrt OTrt

Scheme 2

CO2i-Pr

O

O

O

H

H

H

H

Oi-Pr

OH

O

O

H

H

Oi-Pr

OTi(Oi-Pr)TADDOLate

O

O

H3C CO2i-Pr

CO2HH3C

96% ee

H3C

H3C

CO2i-Pr

CO2H

96% ee

CO2i-Pr

CO2H

>90% ee

CO2H

98% ee

H2O1.2 eq.(Oi-Pr)2TiTADDOLate

THF, 5-6d, - 15 °C

Scheme 3


TADDOL


Ar = 1-Naphthyl

CH2Cl2/Et2O

O

O

H3CH3C

OH

OH

Ar Ar

Ar Ar

OCH3

OCH3

3 eq.MeLi•LiBr (1.2 eq)

-78 °C to -35 °C 75%, 98% ee

Scheme 4

Ar = 1-Naphthyl0.05 eq.

O

O

H3CH3C

OH

OH

Ar Ar

Ar Ar

H3CO

CH3

O

O

i-Pr

i-Pr i-Pr

H3CO O

O

i-Pr

i-Pr i-PrCH3F

88%, 90% ee

Selectfluor®

CH3CN

Scheme 5

TBDMSO

NCH3H3C

O

H Ph

Ar = 1-Naphthyl+

toluene

O

N

Ph

H3C CH3

TBDMSO

O

O Ph

CH3COClCH2Cl2/toluene

-78°, 15 min

70%, 99% ee

O

O

H3CH3C

OH

OH

Ar Ar

Ar Ar

Scheme 6

(4R,5R)-2,2‑Dimethyl-α,α,α′,α′-tetraphenyldioxolane-4,5‑dimethanol

(−)-2,3-O-Isopropylidene-1,1,4,4-tetraphenyl-L-threitol; (−)-trans-α,α′-(2,2-Dimethyl-1,3-dioxolane-4,5-diyl)bis(diphenylmethanol); TADDOL; 1,1,4,4-Tetraphenyl-2,3-O-isopropylidene-L-threitol; (4R,5R)-4,5-Bis(diphenylhydroxymethyl)-2,2-dimethyl-dioxolane[93379‑48‑7]C31H30O4

FW 466.57

O O

H3C CH3

HOOH

265004-250MG 250 mg

265004-1G 1 g

(4S,5S)-2,2‑Dimethyl-α,α,α′,α′-tetraphenyldioxolane-4,5‑dimethanol, 97%

(+)-2,3-O-Isopropylidene-1,1,4,4-tetraphenyl-D-threitol; (4S,5S)-4,5-Bis(diphenylhydroxymethyl)-2,2-dimethyldioxolane; (+)-trans-α,α′-(2,2-Dimethyl-1,3-dioxolane-4,5-diyl)bis(diphenylmethanol)[93379‑49‑8]C31H30O4

FW 466.57

OO

HO

H3C CH3

OH

264997-250MG 250 mg

264997-1G 1 g

Chlorocyclopentadienyl[(4R,5R)-2,2‑dimethyl-α,α,α′,α′-tetra-phenyl-1,3‑dioxolane-4,5‑dimethanolato]titanium, 97%

(4R,5R)-Chloro-cyclopentadienyl-[2,2-dimethyl-1,3-dioxolan-4,5-bis(diphenylmethoxy)]titanium; (R,R)-Duthaler-Hafner reagent; [(4R,5R)-2,2-Dimethyl-1,3-dioxolan-4,5-bis(diphenylmethoxy)]cyclopenta-dienyl-chlorotitanium[132068‑98‑5]C36H33ClO4TiFW 612.96

Ti

O

O

O

O

H3CH3C

Cl

MR: 34 S: 26-36/37/39-45

449520-100MG 100 mg

449520-500MG 500 mg

Chlorocyclopentadienyl[(4S,5S)-2,2‑dimethyl-α,α,α′,α′-tetra-phenyl-1,3‑dioxolane-4,5‑dimethanolato]titanium, 97%

(4S,5S)-Chloro-cyclopentadienyl-[2,2-dimethyl-1,3-dioxolan-4,5-bis(diphenylmethoxy)]titanium; (S,S)-Duthaler-Hafner reagent; [(4S,5S)-2,2-Dimethyl-1,3-dioxolan-4,5-bis(diphenylmethoxy)]cyclopentadienyl-chlorotitanium[140462‑73‑3]C36H33ClO4TiFW 612.96

OTi

OO

O

H3C

H3C

Cl

MR: 34 S: 26-36/37/39-45

449539-500MG 500 mg

(4R,5R)-2,2‑Dimethyl-α,α,α′,α′-tetra(2‑naphthyl)dioxolane-4,5‑dimethanol, 99%

(−)-DINOL; (−)-2,3-O-Isopropylidene-1,1,4,4-tetra(2-naphthyl)-L-threitol[137365‑09‑4]C47H38O4

FW 666.80O O

H3C CH3

HO OH

393754-1G 1 g

(4S-trans)-2,2‑Dimethyl-α,α,α′,α′-tetra(2‑naphthyl)-1,3‑diox-olane-4,5‑dimethanol, 98%

(4S,5S)-2,2-Dimethyl-α,α,α′,α′-tetra(2-naphthyl)dioxolane-4,5-dimethanol; (+)-DINOL; (+)-2,3-O-Isopropylidene-1,1,4,4-tetra(2-naphthyl)-D-threitol[137365‑16‑3]C47H38O4

FW 666.80O O

H3C CH3

HO OH

393762-250MG 250 mg

393762-1G 1 g

(4S-trans)-2,2‑Dimethyl-α,α,α′,α′-tetra(1‑naphthyl)-1,3‑diox-olane-4,5‑dimethanol, 99%

[171086‑52‑5]C47H38O4

FW 666.80

O O

H3C CH3

HO OH

395242-1G 1 g


TADDOL













BOX

C2-symmetric chiral bisoxazolines (BOX) are privileged structures becausethey promote a great number of transformations with unprecedentedselectivity.1 In 1991, in the same Journal of American Chemistry issue,two communications appeared by Evans2 and Corey.3 These twopublications have paved the way for a rapidly and ever-growing numberof examples where BOX ligands are used successfully as chiral ligands.

Evans described the cyclopropanation of alkenes using diazo esterscatalyzed by a complex formed of 406147 and Cu(I)OTf. With theester derived from 2,6‑di-tert-butyl-4‑methylphenol (BHT) it wasfound that the increased steric demand displays increased transselectivity (Scheme 1).2

In a related experiment, Evans announced the first catalyticenantioselective aziridination of styrene.4 Two years later, he reportedon an extension of this preliminary work in a full communication(Scheme 2). Using BOX ligand 405000, complexed to Cu(I)OTf, in thecatalytic enantioselective aziridination of styrene, the BOX ligand havingphenyl substituents proved to be superior to the one bearing stericallydemanding t-Bu groups (Scheme 2).

Recently, Reiser et al. discovered a general route to disubstitutedγ-butyrolactones. In an Cu(I)-catalyzed asymmetric cyclopropanation offurans with diazo esters, bis(4‑isopropyloxazoline) 680192 was used aschiral ligand (Scheme 3). This transformation was carried out on50–100 g scale without a detectable loss of enantioselectivity.5

In his 1991 Journal of American Chemical Society communication,Corey used BOX ligand 405000 in an Fe(III)-catalyzed enantioselectiveDiels–Alder reaction (Scheme 4).3

Two year later, Evans described the Cu(II)-catalyzed version of theenantioselective Diels–Alder reaction of unsubstituted acrylimidesusing BOX ligand 406147 as a chiral Lewis acid.6 The reaction proceededin good yield exhibiting excellent enantioselectivity for the endodiastereoisomer (Scheme 5). From further investigations by Evans et al.,it appears that the best combination is BOX 406147 and Cu(II), and thebest counterions are OTf and SbF6.1

4‑Aryl- and 4‑alkylsubstituted BOX-based catalysts were widely used in alarge number of reactions1 and their behavior can provide a goodrepresentation of their efficiency. But BOX ligands with other structuralmotifs have been successfully used too. BOX ligand 405981 has beenused in the Cu(I)-catalyzed highly enantioselective Mannich reactions toefficiently produce highly functionalized 4‑oxo-glutamic ester derivatives(Scheme 6).7

Recently, Ma et al. reported on the enantioselective CuI/bis(oxazoline)-catalyzed addition of propiolates and terminal ynones to1‑acylpyridinium salt to afford highly functionalized dihydropyridineswith excellent enantioselectivity using 464155 (Scheme 7).8 It is foundthat the carbonyl group adjacent to the alkyne moiety is essential for theenantioselectivity of the addition.

References: (1)(a) Desimoni, G.; Faita, G.; Jørgensen, K. A. Chem. Rev. 2006, 106,3561‑3651. (b) Ghosh, A. K.; Mathivanan, P., Cappiello, J. Tetrahedron: Asymmetry 1998,9, 1‑45. (c) Johnson, J. S.; Evans, D. A. Acc. Chem. Res. 2000, 33, 325‑335. (2) Evans, D. A.;Woerpel, K. A.; Hinman, M. M.; Faul, M. M. J. Am. Chem. Soc. 1991, 113, 726. (3) Corey E.J.; Imai, N.; Zhang, H.-Y. J. Am. Chem. Soc. 1991, 113, 728. (4) Evans, D. A.; Faul, M. M.;Bilodeau, M. T.; Anderson, B. A.; Barnes, D. M. J. Am. Chem. Soc. 1993, 115, 5328‑5329.(5)(a) Jezek, E.; Schall, A.; Kreitmeier, P.; Reiser, O. Synlett 2005, 915‑918. (b) Chhor, R. B.;Nosse, B.; Sörgel, S.; Böhm, C.; Seitz, M.; Reiser, O. Chem. -Eur. J. 2003, 9, 260‑270.(6) Evans, D. A.; Miller, S. J.; Lecta, T. J. Am. Chem. Soc. 1993, 115, 6460‑6461. (7) Juhl, K.;Gathergood, N.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2001, 40, 2995. (8) Sun, Z.; Yu,S.; Ding, Z; Ma, D. J. Am. Chem. Soc. 2007, 129, 9300‑9301.

N N

O O

t-But-BuCu

H3C CH3

R N2BHTO

O CO2BHTR+

OTf

1 mol %

CHCl3, r.t.

ROH

LiAlH4

R = Ph: trans:cis 150:1; >99% eeR = Bn: trans: cis 84:1; >99% ee

Scheme 1

N N

O O

PhPhCuOTf

H3C CH3

H

H

Ar

R

5 mol%PhI=NTs

24 h, r.t.

NAr

R

Ts

H

H

up to 97% ee

Scheme 2

OOCH3

OO

OCH3

O

H

H

O

OH3C

(0.66 mol%)PhNHNH2 (0.70 mol%)

Ethyl diazoacetate (2.67 eq.)

CH2Cl2

85-90% ee

O

O

CHOR

N N

O O

i-Pri-PrCu

TfO OTf

H3C CH3

Scheme 3

NO

O O

N N

O O

PhPh

H3C CH3

10 mol%I2 (0.5 eq.)

cyclopentadiene (3 eq.)

-50°, 1 h, CH2Cl2 O N O

OH

85%endo:exo 97:390:10 er (endo)

FeCl Cl

Scheme 4

NO

O O

R

R

NOO

O

N N

O O

t-But-BuCu

TfO OTf

H3C CH3

endo:exo = 95:5up to 98%ee

10 mol%cyclopentadiene

CH2Cl2

Scheme 5

EtO2C

OR

N

EtO2C

Tos

+

N N

O O

Ph

Ph

Ph

PhCu

TfO OTf

10 mol%

CH2Cl2, r.t. to 40 °C, 20-40 hEtO2C

O

RCO2Et

HNTos

H

70-98%, 78-98% ee

Scheme 6

NCO2CH3

I HC R

NCu

N

O O

I

NCO2CH3

R+

10 mol%

i-Pr2NPr, CH2Cl2, -78°

up to 99% ee

Scheme 7


BOX


2,2‑Bis((4S)-(–)-4‑isopropyloxazoline)propane, 96%

S-4,5-Dihydro-2-(2-((S)-4,5-dihydro-4-isopropyl-oxazol-2-yl)propan-2-yl)-4-isopropyloxazoleC15H26N2O2

FW 266.38

N

O

N

OH3C CH3

CH3

H3C

CH3

CH3

LR: 36 S: 26 Fp: 230 °F

680192-500MG 500 mg

2,2'-Isopropylidenebis[(4S)-4-tert-butyl-2‑oxazoline], 99%

(S,S)-2,2′-Isopropylidene-bis(4-tert-butyl-2-oxazoline)[131833‑93‑7]C17H30N2O2

FW 294.43

N

O

N

OH3C CH3

CH3

H3CH3C

CH3

CH3

CH3

LR: 36/37/38 S: 26-36

406147-50MG 50 mg

406147-250MG 250 mg

2,2′-Methylenebis[(4S)-4-tert-butyl-2‑oxazoline], 99%

(S,S)-2,2′-Methylenebis(4-tert-butyl-2-oxazoline)[132098‑54‑5]C15H26N2O2

FW 266.38

N

O

N

O

CH3

H3CH3C

CH3

CH3

CH3

LR: 36/37/38 S: 26-36

405965-500MG 500 mg

(+)-2,2′-Isopropylidenebis[(4R)-4‑phenyl-2‑oxazoline], 97%

(R,R)-2,2'-Bis(4-phenyl-2-oxazolin-2-yl)propane;(R,R)-2,2′-Isopropylidenebis(4-phenyl-2-oxazoline)[150529‑93‑4]C21H22N2O2

FW 334.41

O

N

O

N

CH3H3C

KR: 23/24/25 S: 26-36-45

406961-250MG 250 mg

406961-1G 1 g

(−)-2,2′-Isopropylidenebis[(4S)-4‑phenyl-2‑oxazoline], 97%

(S,S)-2,2′-Isopropylidenebis(4-phenyl-2-oxazoline); (S,S)-2,2-Bis(4-phenyl-2-oxazolin-2-yl)propane[131457‑46‑0]C21H22N2O2

FW 334.41

N

O

N

OH3C CH3

S: 22-24/25 Fp: 110 °C (230 °F)

405000-250MG 250 mg

405000-1G 1 g

(+)-2,2'-Isopropylidenebis[(4R)-4‑benzyl-2‑oxazoline], 98%

[R(R*,R*)]-(+)-2,2′-Isopropylidenebis(4-benzyl-2-oxazoline); (R,R)-(+)-2,2'-Isopropyl-idenebis(4-benzyl-2-oxazoline)[141362‑77‑8]C23H26N2O2

FW 362.46

N

O

N

OH3C CH3

LR: 36/37/38 S: 26-36

495301-250MG 250 mg

495301-1G 1 g

2,2′-Methylenebis[(4S)-4‑phenyl-2‑oxazoline], 97%

(S,S)-2,2′-Methylenebis(4-phenyl-2-oxazoline)[132098‑59‑0]C19H18N2O2

FW 306.36

N

O

N

O

LR: 36/37/38 S: 26-36 Fp: 110 °C (230 °F)

416428-250MG 250 mg

416428-1G 1 g

2,2′-Bis[(4S)-4‑benzyl-2‑oxazoline], 98%

(S,S)-2,2'-Bis(4-benzyl-2-oxazoline); (S,S)-4,4′-Dibenzyl-2,2′-bi(2-oxazoline)[133463‑88‑4]C20H20N2O2

FW 320.39

N

OO

N

LR: 36/37/38 S: 26-36

405973-250MG 250 mg

405973-1G 1 g

2,2′-Methylenebis[(4R,5S)-4,5‑diphenyl-2‑oxazoline], 99%

(4R,5S,4′R,5′S)-2,2′-Methylenebis(4,5-diphenyl-2-oxazoline)[139021‑82‑2]C31H26N2O2

FW 458.55

N

O

N

O

LR: 36/37/38 S: 26-36

405981-250MG 250 mg

405981-1G 1 g

(4S)-(+)-4-[4-(tert-butyl)phenyl]-α-[(4S)-4-[4-(tert-bu-tyl)phenyl]-2-oxazolidinylidene]-2-oxazolineaceto-nitrile, 97%

8

N

O

HN

OCN

CH3

H3CH3C

CH3

CH3

CH3

Bis[(4S)-4-(4-tert-butylphenyl)-4,5‑dihydro-2‑oxazolyl]acetonitrileC28H33N3O2

FW 443.58

LR: 36/37/38 S: 26

682772-250MG 250 mg

(4S,4'S)-(−)-2,2'-(3‑Pentylidene)bis(4‑isopropyloxazoline),97%

(4S,4'S)-(−)-2,2'-(1-Ethylpropylidene)bis(4,5-dihydro-4-isopropyloxazole); [S-(R*,R*)]-(−)-2,2'-(1-Ethylpropylidene)bis(4,5-dihydro-4-isopropyl-oxazole)[160191‑65‑1]C17H30N2O2

FW 294.43

N

O

HN

OCN

LR: 36/37/38 S: 26-36 Fp: 82 °C (180 °F)

650897-500MG 500 mg

650897-1G 1 g


BOX





















(4S)-(+)-Phenyl-α-[(4S)-phenyloxazolidin-2‑ylidene]-2‑oxazol-ine-2‑acetonitrile, 97%

(S,S)-4-Phenyl-α-(4-phenyloxazolidin-2-ylidene)-2-oxazoline-2-acetonitrile[150639‑33‑1]C20H17N3O2

FW 331.37O

NH

O

N

CN

LR: 36/37/38 S: 26-36

417068-250MG 250 mg

417068-1G 1 g

[3aS-[2(3′aR*,8′aS*),3′aα,8′aα]]-(−)-2,2′-Methylenebis[3a,8a-dihydro-8H-indeno[1,2-d]oxazole], 98%

[175166‑49‑1]C21H18N2O2

FW 330.38 N

O

N

O

LR: 36/37/38 S: 26-36

467073-100MG 100 mg

467073-500MG 500 mg

[3aR-[2(3′aR*,8′aS*),3′aβ,8′aβ]]-(+)-2,2′-Methylenebis[3a,8a-dihydro-8H-indeno[1,2-]oxazole], 98%

[180186‑94‑1]C21H18N2O2

FW 330.38 N

O

N

O

LR: 36/37/38 S: 26-36

464155-500MG 500 mg

(1S,9S)-1,9‑Bis[(tert-butyldimethylsiloxy)methyl]-5‑cyanose-micorrin, ≥97.0% (HPLC)

Semicorrin chiral ligand 2[105251‑52‑3]C24H45N3O2Si2FW 463.80

CN

HNN

O OSi

CH3

CH3H3C

H3CH3C Si

H3CH3C

CH3

CH3

CH3

LR: 36/37/38 S: 26-36

14556-10MG 10 mg

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Z273694Chiral Auxiliaries and Ligands in

Asymmetric Synthesis

Z282626Advanced


Z370029Asymmetric Synthetic

Methodology

Z511811Principles and

Applications of Asymmetric synthesis

Z557544Asymmetric Catalysis on Industrial Scale:

Challenges, Approaches and Solutions



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PYBOX

The PYBOX ligand,1 consisting of a pyridine ring flanked by twooxazoline groups, was introduced in 1989 by Nishiyama.2 PYBOX evolveddirectly from the BOX ligands. In comparing them, two points merit to bementioned: (1) the binding site of PYBOXes is big enough to complexeven lanthanide cations and (2) the rigidity of the tridentate PYBOXscaffold is increased.

In his very first application, Nishiyama showed that isopropyl-PYBOX407151 rhodium(III) catalyst effectively promotes the asymmetrichydrosilylation of ketones giving extremely high enantioselectivities(Scheme 1).3

Li and Wei reported in 2002 the copper(I)-catalyzed enantioselectivedirect-addition of terminal alkynes to imines. The most successful ligandtested was PYBOX 496073 bearing phenyl groups (Scheme 2).4

Recently, Shibasaki's group reported on lanthanum aryl oxide/PYBOX-catalyzed direct asymmetric Mannich-type reactions using atrichloromethyl ketone as a propionate equivalent donor.5 TheLa(OAr)3-i-Pr-PYBOX 407151 + LiOAr system gave products in72 to >99% yield, 8:1 to >30:1 dr, and 92‑98% ee (Table 1).

The chiral indium(III)-PYBOX complex prepared from indium triflate andC2-symmetric chiral PYBOX 673986 was found to be an effective chiralligand for the enantioselective allylation reaction of aldehydes withallyltributylstannane, giving high enantioselectivities.6 Using thismethodology, the chiral steroidal aldehyde could be allylated withexcellent enantioselectivity ((22S):(22R)= >99:1) and in good yield (78%).Furthermore, the reaction was highly chemoselective, reacting only withthe aldehyde functionality. No reaction was observed with the enonefunctionality in the A ring (Scheme 3).

References: (1) Review: Desimoni, G.; Faita, G.; Quadrelli, P. Chem. Rev. 2003, 103,3119‑3154. (2) Nishiyama, H.; Sakaguchi, H.; Nakamura, T.; Horihata, M.; Kondo, M.; Itoh,K. Organometallics 1989, 8, 846‑848. (3) Nishiyama, H.; Park, S.-B.; Itoh, K. Tetrahedron:Asymmetry 1992, 3, 1029‑1034. (4) Wei, C.; Li, C.-J. J. Am. Chem. Soc. 2002, 124,5638‑5639. (5) Morimoto, H.; Lu, G.; Aoyama, N.; Matsunaga, S.; Shibasaki, M. J. Am.Chem. Soc. 2007, 129, 9588‑9589. (6) Lu, J.; Hong, M.-L.; Ji, S.-J.; Loh, T.-P. Chem.Commun. 2005, 1010‑1012.

NO

N N

O

i-Pr i-PrOPh

OHPh

OHPh

+

RhCl ClCl

1 mol%AgBF4, Ph2SiH2

0 °C, 24 h

51%99% ee

49%96% ee

:

NO

N N

O

i-Pr i-Pr

RhCl ClCl

1 mol%AgBF4, Ph2SiH2

0 °C, 2-7 hR CH3

O

R CH3

OH

H3C CO2Et

OHCH3

OH

CH3

OH

91%, 95% ee87%, 94% ee 93%, 92% ee

CH3

OH

91%, 94% ee

Scheme 1

Ar1 H

NAr2

Ph HAr1

**HN

Ar2

Ph

+10 mol%

H2O or toluene

NO

N N

O

Ph Ph

CuOTf

78-96% ee

Scheme 2

S

SN

R H

O

O

CCl3

OH3C

S

SNH

RCH3

CCl3

OOO

+

NO

N N

O

i-Pr i-Pr

LaArO

OArOAr

10 mol%LiOAr (0.5 mol%)

THF/toluene (1:1, 1M)MS 3Å, -40°

(Ar = 4-CH3O-C6H4-)

Entry R % Yield dr (syn:anti) % ee (syn)

1 Ph 96 21:1 96

2 4-Cl-C6H4 97 20:1 96

3 2-thienyl 98 20:1 95

4 cyclohexyl 85 >30:1 96

5 i-Pr 74 >30:1 97

Table 1

NO

N N

O

InTfO

OTfOTf

20 mol%Allyltributylstannane (1.2 eq.)

TMSCl (1.2 eq.)

MS 4Å, CH2Cl2-60 °C, 30 hO

H3C

H3CH3C

O

HH

O

H3C

H3CH3C

OH

H

78%, >99% ee

Scheme 3


PYBOX


2,6‑Bis[(4R)-(+)-isopropyl-2‑oxazolin-2‑yl]pyridine, 99%

[131864‑67‑0]C17H23N3O2

FW 301.38 NN

O O

N

CH3

H3C CH3H3C

LR: 36/37/38 S: 26-36

477494-250MG 250 mg

477494-1G 1 g

2,6‑Bis[(4S)-(−)-isopropyl-2‑oxazolin-2‑yl]pyridine, 99%

(S,S)-2,6-Bis(4-isopropyl-2-oxazolin-2-yl)pyridine; (S,S)-2,2'-(2,6-Pyridinediyl)bis(4-isopropyl-2-oxazoline)[118949‑61‑4]C17H23N3O2

FW 301.38

NN

O O

N

CH3

H3C CH3H3C

LR: 36/37/38 S: 26-36

407151-250MG 250 mg

407151-1G 1 g

2,6‑Bis[(4R)-4‑phenyl-2‑oxazolinyl]pyridine, 98%

(R,R)-2,6-Bis(4-phenyl-2-oxazolinyl)pyridine; (R,R)-2,6-Bis(4,5-dihydro-4-phenyl-2-oxazolyl)pyridine[128249‑70‑7]C23H19N3O2

FW 369.42

NN

OO

N

LR: 36/37/38 S: 26-36/37/39

496065-500MG 500 mg

496065-2G 2 g

2,6‑Bis[(4S)-4‑phenyl-2‑oxazolinyl]pyridine, 98%

(S,S)-2,6-Bis(4-phenyl-2-oxazolinyl)pyridine; (S,S)-2,6-Bis(4,5-dihydro-4-phenyl-2-oxazolyl)pyridine[174500‑20‑0]C23H19N3O2

FW 369.42

NN

OO

N

LR: 36/37/38 S: 26-36/37/39

496073-500MG 500 mg

496073-2G 2 g

2,6‑Bis[(4R,5R)-4‑methyl-5‑phenyl-2‑oxazolinyl]pyridine,97%

NN

OO

N

CH3H3C

2,6‑Bis[(4R,5R)-4,5‑dihydro-4‑methyl-5‑phenyl-2‑oxazolyl]pyridine[312624‑05‑8]C25H23N3O2

FW 397.47

LR: 36/37/38 S: 26-36

496081-500MG 500 mg

2,6‑Bis[(4S,5S)-4‑methyl-5‑phenyl-2‑oxazolinyl]pyridine,98%

NN

OO

N

CH3H3C

2,6‑Bis[(4S,5S)-4,5‑dihydro-4‑methyl-5‑phenyl-2‑oxazolyl]pyridine[185346‑20‑7]C25H23N3O2

FW 397.47

LR: 36/37/38 S: 26-36

496103-500MG 500 mg

2,6‑Bis[(3aS,8aR)-3a,8a-dihydro-8H-indeno[1,2-d]oxazolin-2‑yl]pyridine

(3aS,8aR)-in-pybox; (3aS,3′aS,8aR,8′aR)-2,2′-(2,6-Pyridinediyl)bis[3a,8a-dihydro-8H-indeno[1,2-d]oxazole[185346‑09‑2]C25H19N3O2

FW 393.44

NN

O

N

O

673978-250MG 250 mg

673978-1G 1 g

2,6‑Bis[(3aR,8aS)-(+)-8H-indeno[1,2-d]oxazolin-2‑yl)pyridine

(3aR,8aS)-in-pybox; (3aR,3′aR,8aS,8′aS)-2,2′-(2,6-Pyridinediyl)bis[3a,8a-dihydro-8H-indeno[1,2-d]oxazole[357209‑32‑6]C25H19N3O2

FW 393.44

NN

O

N

O

673986-250MG 250 mg

673986-1G 1 g


PYBOX
















PHOX

Of the thousands of chiral ligands used in asymmetric synthesis arelatively large number exhibit C2-symmetry. More recently,non-symmetrical modular P,N-ligands have been introducedindependently by Pfaltz, Helmchen, and Williams and appliedsuccessfully in various metal-catalyzed reactions.1 Thesephosphinooxazolines (PHOX) are a highly versatile class of ligands.2

PHOX ligand 43158 was successfully used in Pd-catalyzed asymmetricallylic alkylation reactions. Racemic allyl acetates were transformed intotheir Pd allyl complex, which is subsequently attacked by a nucleophile togive the corresponding addition adduct (Scheme 1).1

Phosphinooxazoline 688495 can induce very high enantioselectivities inthe Heck reaction.3 In contrast to analogous reactions withdiphosphine-Pd catalysts, virtually no C=C double bond migration isobserved in the primary product. Hence, particularly in cases wheredouble bond migration leads to undesired products or mixtures ofisomers, phosphinooxazolines are the ligands of choice (Scheme 2).

Cationic iridium-phosphinooxazoline complexes have proved to beeffective catalysts for the enantioselective hydrogenation of imines andtrisubstituted olefins (Scheme 3).4 In a systematic study, PHOX ligandwith a bis(o-tolyl)phosphanyl moiety gave highest enantioselectivities(up to 97% ee).

The cationic iridium complex with PHOX ligand 91716 is an efficientcatalyst for the enantioselective intramolecular Pauson-Khand reaction.5

Under optimized conditions, enantioselectivities of >90% ee wereobtained with 9 mol% of catalyst (Table 1). The anion proved to beimportant, as it had a significant influence on the enantioselectivityand yield. Best results obtained with relatively small, weaklycoordinating anions such as tetrafluoroborate and hexafluorophosphate,but also triflate.

Recently, Rovis et al. used PHOX ligand 688495 in a rhodium(I)-catalyzedenantioselective desymmetrization reaction of meso-3,5‑dimethylglutaric anhydride, providing rapid access to substituted syn-deoxypoly-propionate fragments in a single transformation (Scheme 4).6

References: (1)(a) Von Matt, P.; Pfaltz, A. Angew. Chem., Int. Ed. Engl. 1993, 32, 566.(b) Sprinz, J.; Helmchen, G. Tetrahedron Lett. 1993, 34, 1769. (c) Dawson, G. J.; Frost, C.G.; Williams, J. M. J; Coote, S. J. Tetrahedron Lett. 1993, 34, 3149. (2) Review: Helmchen,G.; Pfaltz, A. Acc. Chem. Res. 2000, 33, 336‑345. (3) (a) Loiseleur, O.; Meier, P.; Pfaltz, A.Angew. Chem., Int. Ed. 1996, 35, 200. (b) Loiseleur, O.; Hayashi, M.; Schmees, N.; Pfaltz, A.Synthesis 1997, 1338. (4) Lightfoot, A.; Schnider, P.; Pfaltz, A. Angew. Chem., Int. Ed. 1998,37, 2897‑2899. For enantioselective reductions of imines using PHOX ligands, see:Schnider, P.; Koch, G.; Prétôt, R.; Wang, G.; Bohnen, F. M.; Krüger, C.; Pfaltz, A. Chem. —Eur. J. 1997, 3, 887‑892. (5) Lu, Z.-L.; Neumann, E.; Pfaltz, A. Eur. J. Org. Chem. 2007,4189‑4192. (6) Cook, M. J.; Rovis, T. J. Am. Chem. Soc. 2007, 129, 9302‑9303.

R R

O

O

CH3

R R

PdNP

O

PhPh

Ph

R R

CO2CH3H3CO2C

99% ee (R = Ph)69-79% ee (R = Alkyl)96% ee (R = i-Pr)

CO2CH3H3CO2C

[Pd(C3H5)]Cl (1-2 mol%)

NP

O

PhPh

Ph

Scheme 1

NP

O

t-BuPh

Ph

O O

6 mol%3 mol% [Pd(dba)2]

Hünig's base, benzene, 2.5 d, r.t.

OTf

+

92%, 99% ee

Scheme 2

CH3

H3CO

CH3

H3CO

50 bar H2

CH2Cl2, r.t.

NP

O

RPh

PhIr

PF6

75% ee (R = i-Pr)90% ee (R = t-Bu)

Scheme 3

PhZ Z

Ph

O

R

9 mol%

CO, 120 °C

NP

O

i-PrPh

PhIr

X

R

Entry Z R X solvent % yield %ee

1 O H OTf DME 85 91

2 O H BF4 DME 89 91

3 O H PF6 DME 93 91

4 NTs H OTf DME 93 81

5 NTs H PF6 DME 95 77

6 C(CO2CH3)2 H BF4 THF 76 91

7 C(CO2CH3)2 H PF6 THF 71 91

8 O CH3 OTf THF 10 71

9 O CH3 BF4 THF 6 64

Table 1

OO O

H3C CH3R

O

CH3

O

OCH3

CH3

10 mol%5 mol% [Rh(nbd)Cl]2

TMSCHN2RZnX or R2Zn (1.7 eq.)

THF, 25-50°C

NP

O

t-BuPh

Ph

H3C

O

CH3

O

OCH3CH3

O

CH3

O

OCH3CH3

FO

CH3

O

OCH3CH3

Ph

O

CH3

O

OCH3CH3

AcO

85%, 95% ee 78%, 91% ee62%, 92% ee 66%, 89% ee

Scheme 4


PHOX


(S)-4-tert-Butyl-2-[2-(diphenylphosphino)phenyl]-2-oxazoline, 97%

8

(4S)-tert-Butyl-2-[2-(diphenylphosphino)phenyl]-4,5-dihydrooxazole[148461‑16‑9]C25H26NOPFW 387.45

N

O

CH3

H3C

H3CP

688495-100MG 100 mg

688495-500MG 500 mg

(R)-(+)-2-[2-(Diphenylphosphino)phenyl]-4‑isopropyl-2‑oxazoline, ≥97.0% (CHN)

(R)-(+)-2-[2-(Diphenylphosphino)phenyl]-4,5-dihydro-4-isopropyl-oxazole[164858‑78‑0]C24H24NOPFW 373.43

N

O

CH3

H3C P

72575-100MG-F 100 mg

72575-500MG-F 500 mg

(S)-(−)-2-[2-(Diphenylphosphino)phenyl]-4‑isopropyl-2‑oxazoline, ≥97.0% (CHN)

(S)-(−)-2-[2-(Diphenylphosphino)phenyl]-4,5-dihydro-4-isopropyloxazole[148461‑14‑7]C24H24NOPFW 373.43

N

O

CH3

H3C P

91716-100MG-F 100 mg

91716-500MG-F 500 mg

(R)-(−)-2-[2-(Diphenylphosphino)phenyl]-4‑phenyl-2‑oxazol-ine, ≥97.0% (31P-NMR)

[167171‑03‑1]C27H22NOPFW 407.44 N

O

P

43158-100MG 100 mg

43158-500MG 500 mg

(S)-(+)-2-[2-(Diphenylphosphino)phenyl]-4‑phenyl-2‑oxazol-ine, ≥97.0% (31P-NMR)

[148461‑15‑8]C27H22NOPFW 407.44 N

O

P

43160-100MG 100 mg

43160-500MG 500 mg

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Dynamic Kinetic Resolution Catalysts

Dynamic Kinetic Resolution (DKR) catalysis is an essential methodology for the conversion of racemic substrates into single enantiomeric products. Kim et al. reported the (S)-selective DKR of a variety of alcohols by utilizing the combination of substilisin and an aminocyclopentadienylruthenium complex. High yields and selectivities were obtained for a variety of secondary alcohols.

R

OH

Ph Ph

NHPhPh

RuOC Cl

CO

686190substilisin, TFEB

THFR

O2CPr

O2CPr

92%, 98% ee

O2CPr

Cl

92%, 99% ee

O2CPr

Ph

90%, 95% ee

Ph Ph

NHPhPh

RuOC Cl

CO

686190

Ph Ph

PhPhPh

RuOC Cl

CO

686441

RuH

RuCO

OCCOCO

Ph

Ph

Ph

Ph

Ph

Ph

Ph

PhPh

Ph

Shvo’s Catalyst 668281

Reference: Kim et al. J. Am. Chem. Soc. 2006, 125, 11494.


PHOX











http://www.sigma-aldrich.com/gochem





Salen Ligands

Salen molecules have been studied for more than six decades. However,in 1990 Jacobsen and Katsuki independently published the first reportsof salen used as ligands with manganese for asymmetric epoxidationreactions.1 Since these first reports, the area of metal-salen catalysis hasexpanded greatly. A plethora of metal-salen complexes have beensynthesized and used in a variety of catalyzed asymmetrictransformations.2 For example, chromium and cobalt salen complexescatalyze the epoxidation of unfunctionalized olefins with high levels ofenantioselectivities.3 Aluminum salen complexes catalyze the conjugateaddition of azide to unsaturated imides.4 The easy synthesis andmodifications of the salen ligand framework made it the platform ofchoice for the discovery of new catalysts and reactions.

Examples of the versatility of the salen complexes are illustrated inScheme 1.

References: (1)(a) Zhang, W. et al. J. Am. Chem. Soc. 1990, 112, 2801. (b) Jacobsen, E. N.et al. J. Am. Chem. Soc. 1991, 113, 6703. (c) Irie, R. et al. Tetrahedron Lett. 1990, 31, 7345.(2)(a) Jacobsen, E. N. In Comprehensive Organometallic Chemistry II; Abel, E. W.; Stone, F.G. A.; Wilkinson, G., Eds.; Elsevier Science: Oxford, 1995; Vol. 12, p 1097. (b) Canali, L.;Sherrington, D. C. Chem. Soc. Rev. 1999, 28, 85. (c) McGarrigle, E. M.; Gilheany, D. G.Chem. Rev. 2005, 105, 1563. (3)(a) Jacobsen, E. N. et al. J. Am. Chem. Soc. 1991, 113,7063. (b) Jacobsen, E. N. Acc. Chem. Res. 2000, 33, 421. (4) Meyers, J.K.; Jacobsen, E. N. J.Am. Chem. Soc. 1999, 121, 8959.

N N

O OM

O

ClO

PhO

Ph

OH

H3C N3

NH

Ph

O O

OH3C

CH3 SiMe3

O OEt

CH3H3C

N3

OH

H3C

OH OSiMe3

Scheme 1

(R,R)-(−)-N,N′-Bis(3,5‑di-tert-butylsalicylidene)-1,2‑cyclo-hexanediamine, 98%

N N

OH HOH3C

H3CH3C

H3CCH3

H3C

CH3H3C

CH3

CH3

CH3H3C

(R,R)-Jacobsen’s ligand[135616‑40‑9]C36H54N2O2

FW 546.83

LR: 36/37/38 S: 26

404411-1G 1 g

404411-5G 5 g

(S,S)-(+)-N,N′-Bis(3,5‑di-tert-butylsalicylidene)-1,2‑cyclo-hexanediamine, 98%

N N

OH HOH3C

H3CH3C

H3CCH3

H3C

CH3H3C

CH3

CH3

CH3H3C

(S,S)-Jacobsen’s ligand[135616‑36‑3]C36H54N2O2

FW 546.83

LR: 36/37/38 S: 26-36

404438-1G 1 g

404438-5G 5 g

(R,R)-N,N'-Bis(3,5‑di-tert-butylsalicylidene)-1,2‑cyclohexane-diaminoaluminum chloride

N

Al

N

O OClH3C

H3CH3C

H3CCH3

H3C

CH3H3C

CH3

CH3

CH3H3C

(R,R)-N,N′-Bis(3,5‑di-tert-butylsalicylidene)-1,2‑cyclohexanediamino-aluminium(III) chloride[250611‑13‑3]C36H52AlClN2O2

FW 607.24

LR: 20/21/22 S: 26-36

531960-1G 1 g

531960-5G 5 g

(S,S)-N,N'-Bis(3,5‑di-tert-butylsalicylidene)-1,2‑cyclohexane-diaminoaluminum chloride

N

Al

N

O OClH3C

H3CH3C

H3CCH3

H3C

CH3H3C

CH3

CH3

CH3H3C

(S,S)-N,N′-Bis(3,5‑di-tert-butylsalicylidene)-1,2‑cyclohexanediaminoalumi-num(III) chloride[307926‑51‑8]C36H52AlClN2O2

FW 607.24

LR: 20/21/22 S: 26-36

531979-1G 1 g


SalenLig

ands









(R,R)-N,N′-Bis(3,5‑di-tert-butylsalicylidene)-1,2‑cyclohexane-diaminochromium(III) chloride

N

Cr

N

O OClH3C

H3CH3C

H3CCH3

H3C

CH3H3C

CH3

CH3

CH3H3C

[164931‑83‑3]C36H52ClCrN2O2

FW 632.26

LR: 20/21/22 S: 26-36

531944-1G 1 g

531944-5G 5 g

(S,S)-N,N′-Bis(3,5‑di-tert-butylsalicylidene)-1,2‑cyclohexane-diaminochromium(III) chloride

N

Cr

N

O OClH3C

H3CH3C

H3CCH3

H3C

CH3H3C

CH3

CH3

CH3H3C

[219143‑92‑7]C36H52ClCrN2O2

FW 632.26

LR: 20/21/22 S: 26-36

531952-1G 1 g

531952-5G 5 g

(R,R)-(−)-N,N′-Bis(3,5‑di-tert-butylsalicylidene)-1,2‑cyclo-hexanediaminocobalt(II)

NCo

N

O OH3C

H3CH3C

H3CCH3

H3C

CH3H3C

CH3

CH3

CH3H3C

[176763‑62‑5]C36H52CoN2O2

FW 603.74

LR: 20/21/22 S: 36/37/39

474592-1G 1 g

474592-5G 5 g

474592-25G 25 g

(S,S)-(+)-N,N′-Bis(3,5‑di-tert-butylsalicylidene)-1,2‑cyclo-hexanediaminocobalt(II)

NCo

N

O OH3C

H3CH3C

H3CCH3

H3C

CH3H3C

CH3

CH3

CH3H3C

[188264‑84‑8]C36H52CoN2O2

FW 603.74

LR: 20/21/22 S: 36/37/39

474606-1G 1 g

474606-5G 5 g

474606-25G 25 g

(R,R)-(−)-N,N′-Bis(3,5‑di-tert-butylsalicylidene)-1,2‑cyclo-hexanediaminomanganese(III) chloride

N

Mn

N

O OClH3C

H3CH3C

H3CCH3

H3C

CH3H3C

CH3

CH3

CH3H3C

Jacobsen’s catalyst; (R,R)-Jacobsen’s catalyst[138124‑32‑0]C36H52ClMnN2O2

FW 635.20

LR: 36/37/38 S: 26-36

404446-1G 1 g

404446-5G 5 g

404446-25G 25 g

(S,S)-(+)-N,N′-Bis(3,5‑di-tert-butylsalicylidene)-1,2‑cyclo-hexanediaminomanganese(III) chloride

N

Mn

N

O OClH3C

H3CH3C

H3CCH3

H3C

CH3H3C

CH3

CH3

CH3H3C

(S,S)-Jacobsen’s catalyst[135620‑04‑1]C36H52ClMnN2O2

FW 635.20

LR: 36/37/38 S: 26-36

404454-1G 1 g

404454-5G 5 g

404454-25G 25 g


SalenLigands


















2,2′-[(1S,2S)-(+)-1,2‑Cyclohexanediylbis[(E)(nitrilomethyl-idyne)]]bis[4-(tert-butyl)-6-(4‑morpholinylmethyl)morpho-linylmethyl)phenol], 97%

N,N′-Bis[(E)-5-(tert-butyl)-2-hydroxy-3,4-morpho-linylmethyl)benzylidene]-[(1S,2S)-1,2-cyclohexane-diamine][252735‑72‑1]C38H56N4O4

FW 632.88 N

N

OH

OH

N

N

O

O

CH3H3CCH3

CH3H3CCH3

LR: 36/37/38 S: 26

673358-250MG 250 mg

2,2′-[(1R,2R)-(–)-1,2‑Cyclohexanediylbis((E)-(nitrilomethyl-idyne))]bis[4-(tert-butyl)-6-(4‑morpholinylmethyl)phenol],97%

N,N′-Bis[(E)-5-(tert-butyl)-2-hydroxy-3-(4-morpho-linylmethyl)benzylidene]-[(1R,2R)-1,2-cyclohexane-diamine][323193‑85‑7]C38H56N4O4

FW 632.88OH

CH3H3CCH3

OH

CH3H3C

CH3

N

N

N

N

O

O

LR: 36/37/38 S: 26

673331-250MG 250 mg

2,2′-[(1S,2S)-1,2‑Cyclohexanediylbis[(E)-(nitrilomethyl-idyne)]]bis[4-(tert-butyl)-6-(4‑piperidinylmethyl)phenol],97%

N,N′-Bis[(E)-5-(tert-butyl)-2-hydroxy-3-4-piperidinylmethyl)benzylidene]-[(1S,2S)-1,2-cyclo-hexanediamine][478282‑27‑8]C40H60N4O2

FW 628.93N

N

OH

OH

N

N

CH3H3C

CH3

H3C CH3CH3

LR: 36/37/38 S: 26

673366-250MG 250 mg

2,2′-[(1R,2R)-1,2‑Cyclohexanediylbis[(E)(nitrilomethylidyne)]bis[4-(tert-butyl)-6-(4‑piperidinylmethyl)phenol], 97%

N,N′-Bis[(E)-5-(tert-butyl)-2-hydroxy-3-4-piperidinylmethyl)benzylidene]-[(1R,2R)-1,2-cyclo-hexanediamine][478282‑28‑9]C40H60N4O2

FW 628.93N

N

OH

OH

N

N

CH3H3C

CH3

H3C CH3CH3

LR: 36/37/38 S: 26

673374-250MG 250 mg

ArCHO Ar' B(OH)2+

(3.3 mol%)[(Rh(C2H4)Cl]2 (3 mol%)KOH

MeOH/H2O50 °C

H3C

Ph

OCH3H3C

CH3

CH3

H

672254

ArCHO

Ar'

CHO

OCH3

80%, 92% ee

CHO

H3CO

H3C O

78%, 93% ee

CHO

CF3

85%, 90% ee

sigma-aldrich.com

Chiral Diene Ligands

The use of chiral diene as ligands for asymmetric synthesis has been growing for the past 5 years. Paquin et al. reported the asymmetric synthesis of 3,3-diarylpropanals using a chiral bicyclo[2.2.2]octadiene as a ligand with a rhodium complex. This new synthesis provides access to building blocks that are otherwise not readily available. Good yields and selectivity were reported with a variety of boronic acids and cinnamaldehydes.

Reference: Carreira, E. M. et al J. Am. Chem. Soc. 2005, 127, 10850.

CH3

Ph

OCH3H3C

CH3

CH3

H

672254

CH3

OCH3H3CH

PhCH3

H3C

669490

Ph

Ph

H

H

698733

H

H

Ph

Ph

698725


SalenLig

ands











Cinchona Alkaloids

Cinchona alkaloids and their derivatives have proven to catalyze anastonishing array of enantioselective transformations, providing access tochiral products of high enantiopurity.1 The presence of the tertiaryquinuclidine nitrogen renders them effective ligands for a variety ofmetal-catalyzed processes. Of these reactions, the osmium-catalyzedasymmetric dihydroxylation of olefins (Scheme 1), developed bySharpless in 1988, has had the greatest impact in synthetic chemistry.2

Bis-(cinchona alkaloid) ligands (which are generally the better catalysts)catalyze the formation of diols of high enantiopurity from a very broadrange of olefins. A recent example stems from O'Doherty et al. where(E,E)- and (E,Z)-1,3‑dienoates were dihydroxylated regioselectively ingood yields and excellent enantioselectivities using (DHQD)2PHAL392731 (Scheme 2).3

Subsequently, these cinchona alkaloids were used for theosmium-catalyzed asymmetric aminohydroxylation of olefins.4 Thesignificance of this reaction is immediately apparent as the asymmetricaminohydroxylation provides straightforward access to theaminoalcohols present in a wide variety of biologically active agentsand natural products.

Kim et al. have published recently a practical new synthetic route to(–)-cassine, which shows antimicrobial activity against Staphylococcusaureus, via asymmetric aminohydroxylation followed by reductiveamination (Scheme 3).5

The nucleophilic quinuclidine nitrogen can also be used directly as areactive center for enantioselective catalysis. Cinchona alkaloidstherefore can be used as bases to deprotonate substrates with relativelyacidic protons forming a contact ion pair between the resulting anionand protonated amine. This interaction leads to a chiral environmentaround the anion and permits enantioselective reactions withelectrophiles.

Important in many of these processes is the ability to control theformation of quaternary asymmetric centers with high enantiomericexcesses. Using the (DHQD)2AQN (456713) catalyst it is possible to affectthe α-functionalization of ketones by the addition of TMSCN to thecorresponding cyanohydrin in excellent yield and enantiomeric excess(Scheme 4).6

The metal-free, allylic amination reaction provides a useful extension tothe conventional palladium catalyzed π-allylic methodology. Aminationwith diimides at the remote γ-position can be carried out using(DHQ)2PYR (418978) to form a diverse range of highly functionalizedamine compounds (Scheme 5).7

Jørgensen et al. have developed the first catalytic enantioselectiveconjugate addition to alkynones using (DHQ)2PHAL (392723).8 For botharomatic and aliphatic alkynones the addition of β-diketones proceeds inhigh yields and enantioselectivity giving a mixture of (E)- and (Z)-enones(Scheme 6).

Dimeric (DHAD)2AQN catalyzes the enantioselective desymmetrization ofmeso anhydrides with methanol by a nucleophilic mechanism(Scheme 7). The scope of the reaction was found to be very general,with excellent enantioselectivity obtained in the desymmetrization ofmonocyclic, bicyclic, and tricyclic prochiral and meso anhydrides.9

References: (1) Kacprzak, K.; Gawronski, J. Synthesis 2001, 961‑998. (2) Kolb, H. C.;VanNieuwenhze, M. S.; Sharpless, K. B. Chem.Rev. 1994, 94, 2483. (3) Ahmed, Md. M.;Mortensen, M. S.; O'Doherty, G. A. J. Org. Chem. 2006, 71, 7741‑7746. (4) Bodkin, J. A.;McLeod, M. D. J. Chem. Soc., Perkin Trans. 1, 2002, 2733‑2746. (5) Kim, G.; Kim, N.Tetrahedron Lett. 2007, 48, 4481‑4483. (6) Tian, S.-K.; Hong, R.; Deng, L. J. Am. Chem.Soc. 2003, 125, 9900‑9901. (7) Poulsen, T.B.; Alemparte, C.; Jørgensen, K. A. J. Am. Chem.Soc. 2005, 127, 11614‑11615. (8)(a) Bella, M.; Jørgensen, K. A. J. Am. Chem. Soc. 2004,126, 5672‑5673. (b) Chen, Y.; Tian, S.-K.; Deng, L. J. Am. Chem. Soc. 2000, 122,9542‑9543.

RL

RS RM

H

AD-mix α RL HRS RM

HO OH

HRLRMRS

OHHO

AD-mix β

Scheme 1

R OEt

O

CH3

R OEt

OOH

HO CH3

1% OsO4, 5% (DHQD)2PHAL3 eq. K3Fe(CN)6, 3 eq. K2CO3, 3 eq. MeSO2NH2

0.2 M t-BuOH/H2O (1:1), 0° to r.t.

68%, 99% ee (R = CH3)70%, 98% ee (R = (CH2)2OTBS)73%, 99% ee (R = (CH2)2OBn)

CH3

CH3

OEt

O

H3CCH3

OEt

OOH

HO

1% OsO4, 5% ligand3 eq. K3Fe(CN)6, 3 eq. K2CO3, 3 eq. MeSO2NH2

0.2 M t-BuOH/H2O (1:1), 0° to r.t.

35%, 70% ee (ligand (DHQD)2PHAL)64%, 73% ee (ligand (DHQD)2PYR)

Scheme 2

H3C

O O

CH310H3C

O O

CH310

NHZ

OH

NH

HO

H3C

O

CH310

Z-NH2, NaOH, t-BuOClK2OsO4•2H2O/(DHQD)2PHAL (cat.)

BuOH/H2O, r.t.

43%, 86% ee

H2, Pd/C (cat.)MeOH, r.t.

(−)-cassine, 85%

Scheme 3


Cinch

onaAlkaloids


Ph

O

OEt

OEtPh

OEt

OEtNC OTMS N

H

N

O

O O

ON

H

N

OCH3H3CO

H3CCH3

H H

2-20 mol% cat.

TMSCN, CHCl3, -50°

(DHQD)2AQN

>80%90-98% ee

Scheme 4

R1

CN

RO2C R2 N NBoc

Boc N N

OO

N

OCH3H3CO

NH3C

H H

N

CH3

(DHQ)2PYR

CN

RO2CR1

N

R2

NHBocBoc

+10 mol%

CH2Cl2, -24°

65-80%86-99% ee

Scheme 5

NNNO O

N N

H3CO OCH3

N

H3CH

H

CH3H

H

(DHQ)2PHAL

O O

R1

O

R2

O O

R1

R2

O+

5 mol%

toluene, r.t.

>95%77-95% ee

Scheme 6

O

O

O

H3C

H3C

H3C CO2H

CO2CH3H3C

(DHQD)2AQN (5-30 mol%)

MeOH, toluene, -40 to -20°C

CO2H

CO2CH3

H

H

99%, 95% ee

CO2H

CO2CH3

H3C CO2H

CO2CH3H3C

93%, 98% ee97%, 97% ee

H

H

OCO2H

CO2CH3

88%, 96% ee

CO2H

CO2CH3H3C

H3C

72%, 90% ee

Scheme 7

Cinchonidine, 96%

(−)-Cinchonidine[485‑71‑2]C19H22N2OFW 294.39

N

N

H2C

OH

S: 22-24/25 EC No. 207-622-3 RTECS # GD2975000

C80407-10G 10 g

C80407-100G 100 g

(+)-Cinchonine, 85%

Cinchonine monohydrochloride dihydrate[118‑10‑5]C19H22N2OFW 294.39

N

N

H2C

OH

LR: 20/22 S: 26-36 EC No. 204-234-6 RTECS # GD3500000

857270-25G 25 g

857270-100G 100 g

857270-250G 250 g

Cinchonine monohydrochloride hydrate, 99%

Cinchonan-9(S)-ol monohydrochloride[312695‑48‑0]C19H22N2O · HCl · xH2OFW 330.85 (Anh)

N

N

H2C

OH • xH2O

• HCl

LR: 20/21/22 S: 36

420328-50MG 50 mg

420328-250MG 250 mg


Cinch

onaAlkaloids

http://www.sigmaaldrich.com/catalog/search/ProductDetail/ALDRICH/C80407

http://www.sigmaaldrich.com/catalog/search/ProductDetail/ALDRICH/C80407







Quinidine, ≥98.0% (NT, dried material)

[56‑54‑2]C20H24N2O2

FW 324.42 N

N

H2C

OHH3CO

LR: 22 S: 36 EC No. 200-279-0 RTECS # VA4725000

22600-10G-F 10 g

22600-50G-F 50 g

Quinine, 90%

[130‑95‑0]C20H24N2O2

FW 324.42 N

N

H2C

OHH3CO

LR: 36/37/38-42/43 S: 22-26-36/37-45 EC No. 205-003-2RTECS # VA6020000

145904-10G 10 g

145904-50G 50 g

Quinine hemisulfate salt monohydrate, 90%

• 1/2

• H2O

H2SO4N

N

H2C

OHH3CO

[6119‑70‑6]C20H24N2O2 · 0.5H2O4S · H2OFW 391.47

LR: 36/37/38 S: 26

145912-5G 5 g

145912-10G 10 g

145912-50G 50 g

Hydrocinchonine, ≥97.0% (GC, sum of enantiomers)

Dihydrocinchonine[485‑65‑4]C19H24N2OFW 296.41

N

N

H3C

OH

≥99.0% (NT)

LR: 20/21/22 S: 36/37 EC No. 207-621-8

54060-500MG 500 mg

Hydroquinidine, 95%

Dihydroquinidine[1435‑55‑8]C20H26N2O2

FW 326.43N

N

H3C

OHH3CO

LR: 20/21/22 S: 36/37 EC No. 215-862-5 RTECS # MX3016000

359343-1G 1 g

359343-5G 5 g

Hydroquinine, 98%

Dihydroquinine[522‑66‑7]C20H26N2O2

FW 326.43N

N

H3C

OHH3CO

LR: 36/37/38 S: 26-36 EC No. 208-334-0

337714-1G 1 g

337714-5G 5 g

Hydroquinidine hydrochloride, 98%

Dihydroquinidine hydrochloride[1476‑98‑8]C20H26N2O2 · HClFW 362.89

N

N

H3C

OHH3CO• HCl

LR: 22 EC No. 216-024-1 RTECS # MX3018000

254819-5G 5 g

254819-25G 25 g

Hydroquinine hydrobromide hydrate, 98%

[207386‑86‑5]C20H26N2O2 · HBr · xH2OFW 407.34 (Anh) N

N

H3C

OHH3CO • xH2O

• HBr

LR: 36/37/38 S: 26-37/39

341320-1G 1 g

O-(4‑Chlorobenzoyl)hydroquinine, 98%

Dihydroquinine 4-chlorobenzoate; Hydroquin-ine 4-chlorobenzoate[113216‑88‑9]C27H29ClN2O3

FW 464.98

N

N

H3C

OH3CO

Cl

O

S: 22-24/25

336491-1G 1 g


Cinch

onaAlkaloids


















Hydroquinidine 4‑chlorobenzoate, 98%

Dihydroquinidine 4-chlorobenzoate; O-(4-Chlorobenzoyl)hydroquinidine[113162‑02‑0]C27H29ClN2O3

FW 464.98

N

N

H3C

OH3CO

Cl

O

LR: 36/37/38 S: 26-36

336483-1G 1 g

336483-5G 5 g

Hydroquinine 4‑methyl-2‑quinolyl ether, 98%

[135096‑79‑6]C30H33N3O2

FW 467.60 N

N

H3C

OH3CO N

CH3

LR: 36/37/38 S: 26-36

381969-1G 1 g

Hydroquinidine 4‑methyl-2‑quinolyl ether, 97%

[135042‑89‑6]C30H33N3O2

FW 467.60 N

N

H3C

OH3CO N

CH3

LR: 36/37/38 S: 26-36

381942-1G 1 g

Hydroquinidine 9‑phenanthryl ether, 96%

O-(9-Phenanthryl)hydroquinidine[135042‑88‑5]C34H34N2O2

FW 502.65N

N

H3C

OH3CO

S: 22-24/25

381950-250MG 250 mg

381950-1G 1 g

Hydroquinine-9‑phenanthryl ether, 97%

O-(9-Phenanthryl)hydroquinine[135096‑78‑5]C34H34N2O2

FW 502.65N

N

H3C

OH3CO

LR: 36/37/38 S: 26-36

381977-100MG 100 mg

381977-500MG 500 mg

(2R,4S,5R)-2‑Aminomethyl-5‑ethylquinuclidine, ≥95.0% (GC)

(2R,4S,5R)-5-Ethyl-2-quinuclidinylmethylamine[475160‑61‑3]C10H20N2

FW 168.28NH2N

H3C

LR: 22-37/38-41 S: 26-39

39867-100MG-F 100 mg

39867-500MG-F 500 mg

(2S,4S,5R)-2‑Aminomethyl-5‑ethylquinuclidine, ≥95.0% (GC)

(2S,4S,5R)-5-Ethyl-2-quinuclidinyl-methylamine[475160‑59‑9]C10H20N2

FW 168.28N

H2N

H3C

LR: 22-38-41 S: 26-39

07317-100MG-F 100 mg

07317-500MG-F 500 mg

(2R,4S,5R)-2‑Hydroxymethyl-5‑ethylquinuclidine, ≥99.0%(GC)

(2R,4S,5R)-5-Ethyl-2-quinuclidinylmethanol[219794‑81‑7]C10H19NOFW 169.26

N

H3C

HO

LR: 37/38-41 S: 26-39

49463-100MG-F 100 mg

49463-500MG-F 500 mg

(2S,4S,5R)-2‑Hydroxymethyl-5‑ethylquinuclidine, ≥99.0%(GC)

(2S,4S,5R)-5-Ethyl-2-quinuclidinylmethanol[219794‑79‑3]C10H19NOFW 169.26

N

H3C

HO

LR: 37/38-41 S: 26-39

51957-100MG-F 100 mg

51957-500MG-F 500 mg

(2R,5R)-(+)-5‑Vinyl-2‑quinuclidinemethanol, 96%

C10H17NOFW 167.25

N

OH

H2C

Fp: 113 °C (235 °F)

472549-250MG 250 mg


Cinch

onaAlkaloids



















(DHQ)2AQN, 95%

N

H3CO

O

N

N

OCH3

O

N

OO

H3C CH3

Hydroquinine anthraquinone-1,4‑diyl diether[176097‑24‑8]C54H56N4O6

FW 857.05

LR: 36/37/38 S: 26-36/37

456705-500MG 500 mg

(DHQD)2AQN, 95%

N

H3CO

O

N

N

OCH3

O

N

OO

CH3 H3C

Hydroquinidine (anthraquinone-1,4‑diyl) diether[176298‑44‑5]C54H56N4O6

FW 857.05

LR: 36/37/38 S: 26-36

456713-500MG 500 mg

(DHQD)2PHAL, ≥95%

N

H3CO

O

N

N

OCH3

O

NNN

H3CCH3

Hydroquinidine 1,4‑phthalazinediyl diether[140853‑10‑7]C48H54N6O4

FW 778.98S: 22-24/25

392731-1G 1 g

(DHQD)2Pyr, 97%

N

H3CO

O

N

N

OCH3

O

N

NN

CH3 H3C

Hydroquinidine-2,5‑diphenyl-4,6‑pyrimidinediyl diether[149725‑81‑5]C56H60N6O4

FW 881.11

LR: 36/37/38 S: 26-36

418951-1G 1 g

(DHQ)2PHAL, ≥95%

N

H3CO

O

N

N

OCH3

O

NNN

H3C CH3

Hydroquinine 1,4‑phthalazinediyl diether[140924‑50‑1]C48H54N6O4

FW 778.98S: 22-24/25

392723-500MG 500 mg

(DHQ)2Pyr, 97%

N

H3CO

O

N

N

OCH3

O

N

NN

H3C CH3

Hydroquinine 2,5‑diphenyl-4,6‑pyrimidinediyl diether[149820‑65‑5]C56H60N6O4

FW 881.11

LR: 36/37/38 S: 26-36

418978-250MG 250 mg

418978-1G 1 g

AD-mix-α

N

N

NN

N

OCH3H3COH

N

H3C

H

CH3

392758-10G 10 g

392758-50G 50 g

AD-mix-β

N

N

NN

N

OCH3H3COH

N

H3C

H

CH3

392766-10G 10 g

392766-50G 50 g


Cinch

onaAlkaloids













QuinoxP* Ligands

Various optically active phosphine ligands incorporating a chiral center atthe phosphorus display exceptional enantiosectivities in metal-catalyzedasymmetric synthesis.1 For instance, known classes of P-chiral phosphineligands offer good to excellent enantiocontrol in Ru- and Rh-catalyzedhydrogenation reactions.2 The one limitation associated with theseligands is their sensitivity to air, which has impeded widespreadapplicability in bench-top chemistry. Imamoto and co-workers haveaddressed this deficiency through the invention of QuinoxP*, whichcontains an electron-withdrawing quinoxaline architecture.3

The reactivity profile of these innovative, chiral ligands is presented andhighlights the impressive breadth of valuable transformations mediatedby QuinoxP*. These powerful efficient ligands exhibit high levels ofenantiocontrol in synthetic transformations ranging from metal-catalyzedasymmetric 1,4‑additions of arylboronic acids, to enantioselectivealkylative ring opening, to asymmetric hydrogenations.3 It is worthnoting that QuinoxP* is not oxidized at the stereogenic phosphoruscenter on standing at ambient temperature in air for more than9 months.

Highly AsymmetricRhodium-Catalyzed HydrogenationImamoto has gone to great lengths to develop enantiomerically pureP-chiral ligands for industrially useful transformations such as asymmetrichydrogenation. Impressively, a diverse array of prochiral amino acid andamine substrates were hydrogenated with great efficiency to yield highlyenantiopure amine derivatives (Scheme 1). The authors carried out theseexperiments at room temperature in methanol under low hydrogenpressures (3 atm). Note that all hydrogenation reactions were completein 6 hours and with enantiomeric excesses ranging from 96 to 99.9%.Dramatic stereochemical reversal, consistent with the results observedwith the related (S,S)-tert-Bu-BisP* ligands,4,5 was obtained when1‑acetylamino-1‑adamantylethene was hydrogenated to afford theS configuration amine with >96% enantioselectivity (Table 1).

Asymmetric 1,4‑additions of Arylboronic AcidsImamoto and co-workers exploited the high activity of the QuinoxP*ligand in rhodium-catalyzed enantioselective 1,4‑additions of arylboronicacids to α,β-unsaturated carbonyl substrates.3 High yields of the additionproducts were obtained via running the reactions between 40 and50 ºC (Scheme 2). The exceptional enantiocontrol exerted by thisRh(I)-catalyzed system is evident when compared to the use of BINAP asthe chiral ligand.6

Asymmetric Pd-catalyzed Ring OpeningImamoto and co-workers have also succeeded in developing aPd-catalyzed C–C bond-forming reaction, which displays highenantioselectivities with both dimethyl- and diethylzinc (Scheme 3,Table 2). This alkylative ring-opening methodology entails simplypremixing PdCl2(cod) and QuinoxP* for 2 hours at room temperature—leading to a highly active catalyst. This catalyst system affords excellentyields of the ring-opened products and selectivities that rival the highestreported for this transformation. These results, when combined with theoutstanding methodologies presented, indicate that QuinoxP* is usefulfor a broad variety of asymmetric metal-catalyzed transformations.

References: (1)(a) Weinkauff, D. J. et al. J. Am. Chem. Soc. 1977, 99, 5946. (b) Spagnol,M. et al. Chem. -Eur. J. 1997, 3, 1365; (c) Hamada, Y. et al. Tetrahedron Lett. 1997, 38,8961; (d) Kurth, V. et al. Eur. J. Inorg. Chem. 1998, 597. (e) Mezzetti, A. et al.Organometallics 1998, 17, 668. (f) Imamoto, T. et al. J. Am. Chem. Soc. 1998, 120, 1635.(g) Mezzetti, A. et al. Organometallics 1999, 18, 1041. (h) Imamoto, T. J. Org. Chem. 1999,64, 2988. (i) Imamoto, T. et al. Tetrahedron: Asymmetry 1999, 10, 877. (j) van Leeuwen, P.W. N. M. et al. J. Org. Chem. 1999, 64, 3996. (2) (a) Zhang, Z. et al. J. Org. Chem. 2000, 65,6223. (b) Tang, W. et al. J. Am. Chem. Soc. 2003, 125, 9570. (c) Lei, A. et al. J. Am. Chem.Soc. 2004, 126, 1626. (d) Tang, W.; Zhang, X. Angew. Chem., Int. Ed. Engl. 2002, 41, 1612.(e) Tang, W.; Zhang, X. Org. Lett. 2002, 4, 4159. (f) Tang, W. et al. Org. Lett. 2003, 5, 205.(g) Tang, W. et al. Angew. Chem., Int. Ed. 2003, 42, 3509 (h) Xiao, D. et al. Org. Lett. 1999,1, 1679. (i) Liu, D.; Zhang, X. Eur. J. Org. Chem. 2005, 646. (3) Imamoto, T.; Sugita, K.;Yoshida, K. J. Am. Chem. Soc. 2005,127, 11934. (4) Imamoto, T. et al. J. Am. Chem. Soc.2000, 122, 10486. (5) Imamoto, T. et al. J. Am. Chem. Soc. 2001, 123, 5268.(6)(a) Miyaura, N. et al. J. Am. Chem. Soc. 1998, 120, 5579. (b) Hayashi, T. et al.Tetrahedron Lett. 1999, 40, 6957.

N

N

P

P

CH3t-Bu

t-BuH3CNHAc

R1 R2

R3 1 mol% [Rh(nbd)2]BF4

H2, MeOH, 6 h

NHAc

R1 R2

R3

*

96 - 99% ee

Scheme 1

Entry R1 R2 R3 ee (%) (confi g)

1 CO2CH3 Ph H 99.9 (R)

2 CO2CH3 4-AcO-3-MeOC6H3 H 99.6 (R)

3 CH3 H CO2CH3 99.7 (R)

4 CH3 CO2CH3 H 99.2 (R)

5 Ph H H 99.9 (R)

6 1-adamantyl H H 99.3 (S)

Table 1

N

N

P

P

CH3t-Bu

t-BuH3C

(3 mol%)

[RhCl(C2H4)2]2 (3 mol%)PhB(OH)2, KOH , dioxane/H2O, 1 h

97%, 99% ee

O OPh

Scheme 2

N

N

P

P

CH3t-Bu

t-BuH3C

(5 mol%)

PdCl2(cod) (5 mol%)R2

2Zn, Ch2Cl2, rt

OR1

R1

OHR2

Scheme 3

Entry R1 R2 Time (h) Yield (%) ee (%) (confi g)

1 H CH3 2 90 95.6

2 H CH2CH3 15 88 97.6

3 F CH3 2 90 93.8

Table 2


QuinoxP*Lig

ands


(S,S)-2,3-Bis(tert-butylmethylphosphino) quinoxaline 8

(S) QuinoxP®

C18H28N2P2FW 334.38

N

N

P

P

H3CH3C

CH3

CH3

CH3H3CH3C

CH3

LR: 22-36/37/38 S: 26

694215-100MG 100 mg

(R,R)-(–)-2,3‑Bis(tert-butylmethylphosphino)quinoxaline,97%

(R) QuinoxP®

C18H28N2P2FW 334.38

N

N

P

P

H3CH3C

CH3

CH3

CH3H3CH3C

CH3

LR: 22-36/37/38

676403-100MG 100 mg

676403-500MG 500 mg

sigma-aldrich.com

L-Proline, the archetype

of modern asymmetric

organocatalysts

Organocatalysis

Features include:

• Proline Analogs

• MacMillan

Imidazolidinone

OrganoCatalysts™

• Chiral Phosphoric Acids

• Jacobsen Thioureas

• Cinchona Alkaloids

Vol. 7, No. 9

Organocatalysis provides convenient new methods to construct complex chiral compounds with operational simplicity and without the need for metals. Excellent selectivities are observed in various asymmetric organocatalyzedtransformations.

Sigma-Aldrich® is pleased to offer an expanding portfolio of innovative organocatalysts to accelerate your research success.

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To see a comprehensive listing of organocatalysts, please visit sigma-aldrich.com/organocat

684341

NH HN N

NN

677183

NH O Si

CH3

CH3

CH3

681520

OP

O O

OH

CF3

CF3

CF3

CF3

671428

NH O

CH3

CH3

CH3H3C

Si

CH3

CH3CH3

• HCl

677019

NH O

CF3

CF3

CF3F3C

Si

CH3

CH3CH3

P0380

NH

O

OH


QuinoxP*Ligands





http://www.sigma-aldrich.com/organocat

http://www.sigmaaldrich.com/catalog/search/ProductDetail?ProdNo=P0380&Brand=SIAL







DIPAMP

Rewarded by a Nobel Prize in 2001 for his pioneering work in asymmetricsynthesis, Knowles was the first to develop a transition-metal chiralcatalyst based on a chiral diphosphine ligand, DIPAMP, that could transferchirality to a prochiral substrate with high enantiomeric excesses. Hedemonstrated that a chiral diphosphine chelated to rhodium could giveaccess to catalysis mimicking enzyme selectivity. To demonstrate theactivity and selectivity of this new ligand, Knowles synthesized L-DOPA, atreatment for Parkinson's disease, requiring the selective hydrogenationof an alkene. The synthesis of L-DOPA starts with the asymmetrichydrogenation of (Z)-2‑acetamido-3-(3,4‑dihydroxyphenyl)acrylic acidusing the Rh-DIPAMP complex followed by deprotection of the amine.This process has been scaled up at Monsanto (Scheme 1).1

Reference: (1) Knowles, W. S. Acc. Chem. Res. 1983, 16, 106.

HO

HOOH

O

NH2

HO

HOOH

O

HN O HO

HOOH

O

HN OH2

L-DOPA

95% ee

P

P

Rh

H3CO

H3CO

Scheme 1

(R,R)-DIPAMP, ≥95%

[(1R,2R)-(−)-Bis[(2-methoxyphenyl)phenylphos-phino]ethane]; (R,R)-Ethylenebis[(2-methoxy-phenyl)phenylphosphine][55739‑58‑7]C28H28O2P2FW 458.47

PP

OCH3

H3CO

LR: 36/37/38 S: 26-36/37

461865-500MG 500 mg

461865-1G 1 g

(S,S)-DIPAMP

(1S,2S)-(+)-Bis[(2-methoxyphenyl)phenylphos-phino]ethane[97858‑62‑3]C28H28O2P2FW 458.47

PP

OCH3

H3CO

≥95%

461873-250MG 250 mg

461873-1G 1 g

DIOP

DIOP is one of the first chiral ligands used for asymmetric hydrogenationcatalysis. DIOP can be synthesized in four simple steps from tartaric acid.Chelation with a rhodium complex generates an optically active catalystactive in hydrogenation. To demonstrate the activity of DIOP, Kagan andDang conducted the asymmetric hydrogenation of a variety of alkenes.1

Optical yields of up to 72% were obtained with substrate to catalyst ratioof up to 200:1 (Scheme 1).

References: (1)(a) Dang, T. P.; Kagan, H. B. Chem. Commun. 1971, 481. (b) Kagan, H. B.;Dang, T. P. J. Am. Chem. Soc. 1972, 94, 6429.

O O

Ph2P PPh2

CH3H3CH COOH

HNCH3

O

∗

95%, 72% ee

H COOH

HNPh

O

∗

96%, 64% ee

H COOCH3

HNCH3

O

∗

90%, 55% ee

H CONH2

HNCH3

O

72%, 71% ee

Scheme 1

(+)-2,3-O-Isopropylidene-2,3‑dihydroxy-1,4‑bis(diphenyl-phosphino)butane, 98%

(+)-1,4-Bis(diphenylphosphino)-1,4-dideoxy-2,3-O-isopropylidene-D-threitol; (4S,5S)-4,5-Bis(diphenyl-phosphinomethyl)-2,2-dimethyl-1,3-dioxolane; (S,S)-DIOP; (4S-trans)-[(2,2-Dimethyl-1,3-dioxolane-4,5-diyl)bis(methylene)]bis(diphenylphosphine); (+)-DIOP[37002‑48‑5]C31H32O2P2FW 498.53

O O

CH3H3C

P P

LR: 36/37/38 S: 26 EC No. 253-307-9

237663-50MG 50 mg

237663-1G 1 g

(−)-2,3-O-Isopropylidene-2,3‑dihydroxy-1,4‑bis(diphenyl-phosphino)butane, 98%

(4R,5R)-4,5-Bis(diphenylphosphino-methyl)-2,2-dimethyl-1,3-dioxolane; (4R-trans)-[(2,2-Dimethyl-1,3-dioxolane-4,5-diyl)bis(methylene)]bis(diphenyl-phosphine); (R,R)-DIOP; (−)-1,4-Bis(diphenylphos-phino)-1,4-dideoxy-2,3-O-isopropylidene-L-threitol[32305‑98‑9]C31H32O2P2FW 498.53

OO

CH3H3C

P P

LR: 36/37/38 S: 26-36/37 EC No. 250-984-2

237655-250MG 250 mg

237655-1G 1 g


DIPA

MP/D

IOP










Trost Ligands

Palladium-catalyzed asymmetric allylic alkylation (AAA) has proven to bean exceptionally powerful method for the efficient construction ofstereogenic centers. In sharp contrast to many other catalytic methods,AAA has the ability to form multiple types of bonds (C–C, C–O, C–S,C–N) with a single catalyst system.

PdLn* R X

R'

R X

R'

LnPd*

complexation

–XPdLn*

R R'

PdLn*

R

R'

ionizationNu

R R'LnPd*

Nu

* R'RPdLn

*

Nu

*or

R R'

Nu

*

R'R

Nu

*

or

nucleophilic addition

The Trost group at Stanford University has pioneered the use of C-2symmetric diaminocyclohexyl (DACH) ligands in AAA, allowing for therapid synthesis of a diverse range of chiral products with a limitednumber of chemical transformations. Reactions are typicallyhigh-yielding, and excellent levels of enantioselectivity are observed.1

NH HNOO

PPh2 Ph2P

NH HNOO

PPh2 Ph2P

NH HNOO

PPh2 Ph2P

NH HNOO

PPh2 Ph2P

NH HNOO

NN

NH HNOO

NN

DACH-Phenyl DACH-Naphthyl DACH-Pyridyl

S,S

R,R

Carbon NucleophilesIn early examples of this methodology, Trost and co-workers demon-strated diesters are competent nucleophiles for the deracemization ofcyclic allylic acetates, to afford chiral malonate derivatives. Since thattime, soft carbon nucleophiles such as barbituric acid derivatives, β-ketoesters, nitro compounds, and many others have been employed in AAAfor assembly of tertiary and quaternary asymmetric centers.

OAc

( )n

n = 1, 2, 3

( )n

E

EAPC

DACH-phenyl ligandTHAB, CH2Cl2

E E

Na

81–86%, 93–98% ee

* for n = 1, intermediate to isoiridomyrmecin, α-skyanthine, and 12-oxophytodienoic acid

E = CO2CH3

Malonate Nucleophiles2

APC (0.5 mol %) (S,S)-DACH-phenyl (1.5

mol %)TMG, toluene, 0 ºC

81%, 86% ee

OCO2Et

OAc

OCO2Et steps

HN

OHH

(–)-nitramine

β-Keto Ester Nucleophiles3

Oxygen NucleophilesCarbon-oxygen bond-forming reactions using palladium-catalyzedasymmetric allylic alkylation have been well-demonstrated innumerous natural product syntheses. Alcohols, carboxylates, andhydrogencarbonates have all been employed as O-nucleophiles.

Pd2(dba)3•CHCl3 (R,R)-DACH-ligand

TBAC, CH2Cl2

ArOH

OO

BocOO

O

H

ArO high yields and enantioselectivities

intermediates to brefeldin A and aflatoxin B1

Alcohol Nucleophiles4

Pd2(dba)3•CHCl3 (2.5 mol %)(R,R)-DACH-phenyl (7.5 mol %)

THAB, CH2Cl2

t-BuCO2Na

98%, 93% ee

CO2CH3

OCO2CH3

racemic

CO2CH3

O t-Bu

O

(+)-phyllanthocin intermediate

Carboxylate Nucleophiles5

Nitrogen NucleophilesA formidable challenge in asymmetric synthesis is the stereocontrolledconstruction of carbon-nitrogen bonds. Nitrogen nucleophiles such asalkylamines, azides, amides, imides, and N-heterocycles have all beenemployed in asymmetric allylic alkylation reactions.

APC

(S,S)-DACH-phenylTHF, NEt3

NHPMB OAc

NPMB

H

97%, 91% ee

Alkylamines Nucleophiles6

APC (0.25 mol%)(R,R)-DACH-phenyl (0.75 mol %)

CH2Cl2, rt82%, 95% ee

O

O

OCO2CH3

OCO2CH3

O

O

OCO2CH3

N3

TMSN3

(+)-pancratistatin intermediate

Azide Nucleophiles7

Pd2(dba)3•CHCl3 (2.5 mol%)

DACH-phenyl ligand (7.5 mol %)

Et3N, CH2Cl2 95%, 97% ee

intermediates to mannostatin A and (–)-swainsonine

TsHN(O)CO

TsHN(O)CO

NTs

OO

NTs

OO or

Imide Nucleophiles8


Trost

Ligands


Molybdenum-Catalyzed ReactionsThe mechanism of the molybdenum-catalyzed AAA reaction is presumedto be distinctly different from the analogous Pd-catalyzed reaction, andin some cases, the levels of regio-, enantio-, and diastereoselectivity areenhanced relative to the palladium-catalyzed reaction. Trost and Dograreport the total synthesis of (–)-Δ9-trans-tetrahydrocannabinol, apsychomimetic of marijuana, utilizing a molybdenum catalyst.9 Anoverall yield of 30% of enantiomerically pure (–)-Δ9-trans-tetrahydro-cannabinol (Scheme 1).

References: (1)(a) Trost, B. M.; Fandrick, D. R. Aldrichimica Acta 2007, 40, 59. (b) Trost, B.M. et al. Acc. Chem. Res. 2006, 39, 747. (c) Trost, B. M. J. Org. Chem. 2004, 69, 5813.(d) Trost, B. M.; Crawley, M. L. Chem. Rev. 2003, 103, 2921. (e) Trost, B. M.; Van Vranken,D. L. Chem. Rev. 1996, 96, 395. (f) Trost, B. M. Acc. Chem. Res. 1996, 29, 355. (2)(a) Trost,B. M.; Bunt, R. C. J. Am. Chem. Soc. 1994, 116, 4089. (b) Ernst, M.; Helmchen, G. Synthesis2002, 1953. (c) Ernst, M.; Helmchen, G. Angew. Chem., Int. Ed. 2002, 41, 4054. (3) Trost,B. M. et al. J. Am. Chem. Soc. 1997, 119, 7879. (4)(a) Trost, B. M.; Toste, F. D. J. Am. Chem.Soc. 1999, 121, 3543. (b) Trost, B. M.; Toste, F. D. J. Am. Chem. Soc. 2003, 125, 3090.(c) Trost, B. M.; Crawley, M. L. J. Am. Chem. Soc. 2002, 124, 9328. (d) Trost, B. M.; Crawley,M. L. Chem.-Eur. J. 2004, 10, 2237. (5) Trost, B. M.; Kondo, Y. Tetrahedron Lett. 1991, 32,1613. (6) Trost, B. M. et al. J. Am. Chem. Soc. 1996, 118, 6297. (7)(a) Trost, B. M.; Pulley, S.R. J. Am. Chem. Soc. 1995, 117, 10143. (b) Trost, B. M. et al. Chem.-Eur. J. 2001, 7, 1619.(8)(a) Trost, B. M.; Van Vranken, D. L. J. Am. Chem. Soc. 1993, 115, 444. (b) Trost, B. M. etal. J. Am. Chem. Soc. 1992, 114, 9327. (c) Trost, B. M.; Patterson, D. E. J. Org. Chem. 1998,63, 1339. (9) Trost, B. M.; Dogra, K. Org. Lett. 2007, 9, 861.

Mo(C7H8)(CO)3 (5 mol%)(S,S)-DACH-pyridyl (7.5 mol %)

THF 95%, 94% ee

OCH3

OCH3

OCO2CH3

C5H11E

ENa

H3CO

OCH3C5H11

EE

E = CO2CH3

O

OHC5H11

Scheme 1

(R,R)-DACH-naphthyl Trost ligand, 95% 8

HNNHOO

P P

(1R,2R)-(+)-1,2‑Diaminocyclohexane-N,N′-bis(2‑diphenylphosphino-1‑naphthoyl)[174810‑09‑4]C52H44N2O2P2FW 790.87

692778-250MG 250 mg

692778-1G 1 g

(S,S)-DACH-Naphthyl Trost Ligand, 95% 8

HNNHOO

P P

(1S,2S)-(–)-1,2‑Diaminocyclohexane-N,N′-bis(2‑diphenylphosphino-1‑naphthoyl)[205495‑66‑5]C52H44N2O2P2FW 790.87

692786-250MG 250 mg

692786-1G 1 g

(R,R)-DACH-phenyl Trost ligand, 95% 8

HNNHOO

P P

(1R,2R)-(+)-1,2‑Diaminocyclohexane-N,N′-bis(2‑diphenylphosphino-benzoyl)[138517‑61‑0]C44H40N2O2P2FW 690.75

692808-250MG 250 mg

692808-1G 1 g

(S,S)-DACH-phenyl Trost ligand, 95% 8

HNNHOO

P P

(1S,2S)-(–)-1,2‑Diaminocyclohexane-N,N′-bis(2‑diphenylphosphino-benzoyl)[169689‑05‑8]C44H40N2O2P2FW 690.75S: 36/37/39

692794-250MG 250 mg

692794-1G 1 g

(R,R)-DACH-pyridyl Trost ligand, 95% 8

(–)-N,N′-(1R,2R)-1,2-Diaminocyclohexanediylbis(2-pyridinecarboxamide)[218290‑24‑5]C18H20N4O2

FW 324.38

HNNHOO

N N

692751-500MG 500 mg

692751-1G 1 g

(S,S)-DACH-pyridyl Trost ligand, 95% 8

(1S,2S)-(+)-1,2-Bis[(2-pyridinylcarbonyl)amino]cyclo-hexane; (1S,2S)-N,N′-1,2-Cyclohexanediylbis(2-pyri-dinecarboxamide); (1S,2S)-1,2-Bis(2-pyridinecarboxamido)cyclohexane; (+)-N,N′-(1S,2S)-1,2-Diaminocyclohexanediylbis(2-pyridinecarbox-amide)[172138‑95‑3]C18H20N4O2

FW 324.38

HNNHOO

N N

LR: 22-36/37/38 S: 26

692743-500MG 500 mg

692743-1G 1 g


Trost

Ligands














Landis Ligands

The interest in asymmetric reactions has been growing for the past40 years. To address the challenges of synthesizing chiral building blockswith high yields and high selectivities, researchers developed a broadrange of catalysts. Two of the essential components for highly active andselective catalysts are the ligand and the metal. Professor Landis andco-workers developed a series of new ligands based on chiral3,4‑diazaphospholane structures (Figure 1). These ligands are highlyactive for enantioselective hydroformylation and enantioselective allylicalkylation reactions. These two transformations are essential to access avariety of chiral blocks for the synthesis of more complex molecules.

Synthesis of Isoxazolines and ImidazolesThe asymmetric hydroformylation reaction is a highly chemoselectivetransformation allowing the conversion of terminal olefins into opticallyactive aldehydes. Despite the recognized powerful methodology of thistransformation, it has been sporadically utilized on a commercial scaledue to the low reaction rates, the challenges to control the region- andenantioselectivities simultaneously and the limited substrate scope.Professor Landis and coworkers developed a new family of ligands basedon 2,5‑disubstituted phospholane addressing these issues.Utilizing this newly developed ligand, Thomas and coworkers synthesizeda series of oxazolines and imidazoles.1 Reacting vinyl acetate withRh(CO)2(acac) and (R,R,R) or (S,S,S)-Diazaphos-SPE in a reactor withCO and H2 at 400 psi yielded the corresponding chiral aldehydes with94% conversion and 96% ee (Scheme 1). It is important to note that acatalyst loading of only 0.001 mol% is necessary to complete thistransformation. Following this reaction Thomas and coworkers ensuredthe conservation of the enantioselectivity by synthesizing the isoxazolinesand imidazoles with overall good yields.

Asymmetric Allylic AlkylationThe asymmetric allylic alkylation reaction is an attractive reaction to forma new C–C bond with a desired nucleophile enantioselectively.Professor Landis and co-workers utilized this reaction to test newlysynthesized chiral 3,4‑diazaphospholanes (Diazaphos-PPE).2 With thepresence of a palladium catalyst, these new ligands yielded outstandingconversions and enantioselectivities with a variety of substrates. Using1,3‑diphenylallyl acetate and 2‑penten-4‑yl acetate as reactants, withdimethyl malonate as the nucleophile, Clark and Landis demonstratedthat Diazaphos-PPE is surpassing other ligands with high yields andselectivities for both substrates (Scheme 2).

References: (1) Thomas et al. Org. Lett. 2007, 9, 2665. (2) Clark, T. P. ; Landis, C. R. J. Am.Chem. Soc. 2003, 125, 11792.

N

O

N

O

P Ph

R

R

NN

P

O

O

NN

P

O

O

Diazaphos-PPE Diazaphos-SPE

R R

R R

R: NH

O

Figure 1

OAc

Diazaphos-SPE (0.0012 mol %)Rh(CO)2acac (0.001 mol %)

CO/H2 (400 psi), THF

∗∗

OAc

CHO∗∗

OAc

NOH

NH2OH•HCl

pyridine

OAc

NO

OAc

NOH

Cl

OAc

NOH

NPh

OAc

NOCOC6F5

NPh C6F5COCl

NEt3

N N

OAc

CH3

Ph

H3C

H3CH3CH3C H3C

ON

OAcH3C

XX

X = Ph, 64% p-MeOPh, 65% 4-pyridyl, 80%

allylbenzyl-amine

Pd(PPh3)4

NEt3

63%

(R) or (S)94% yield96% ee

(R) or (S)

NaOClcat. NEt3

NCS

H3C H3C

Scheme 1

R R

OAc (η3-C3H5PdCl)2 (2 mol %)Diazaphos-PPE (4 mol %)

CH2(CO2Me)2, AgPF6,CH2Cl2, NaOAc

R∗∗

R

O

MeO

O

OMe

R= Me, Ph >95% yield91% ee

Scheme 2


Landis

Ligands


(S,S,S)-DiazaPhos-PPE 8

2,2′-[(1S,3S)-2,3,5,10-Tetrahydro-5,10-dioxo-2-phenyl-1H-[1,2,4]diazaphospholo[1,2-b]phthal-azine-1,3-diyl]bis[N-(1S)-1-phenylethyl]benzamide[615538‑63‑1]C46H39N4O4PFW 742.80

NN

P

O

O O

NH

HN

CH3

O CH3

685240-100MG 100 mg

685240-500MG 500 mg

(R,R,S)-DiazaPhos-PPE 8

2,2′-[(1R,3R)-2,3,5,10-Tetrahydro-5,10-dioxo-2-phenyl-1H-[1,2,4]diazaphospholo[1,2-b]phthalazine-1,3-diyl]bis[N-[(1S)-1-phenylethyl]benzamide][615257‑74‑4]C46H39N4O4PFW 742.80

NN

P

O

O O

NH

HN

CH3

O CH3

685089-100MG 100 mg

685089-500MG 500 mg

Bis[(S,S,S)-DiazaPhos-SPE] 8

NN

O

O

P

O

HNCH3

NN

O

O

P

O

NHH3C

O

HNCH3

O

NHH3C

2,2′,2″,2′′′-(1,2‑Phenylenebis[(1S,3S)-tetrahydro-5,8‑dioxo-1H-[1,2,4]diazaphospholo[1,2-a]pyridazine-2,1,3(3H)-triyl])tetrakis(N-[(1S)-1‑phenylethyl])benzamide[851770‑14‑4]C78H72N8O8P2FW 1311.40

685259-100MG 100 mg

685259-500MG 500 mg

Bis[(R,R,S)-DiazaPhos-SPE] 8

NN

O

O

P

O

HNCH3

NN

O

O

P

O

NHH3C

O

HNCH3

O

NHH3C

2,2′,2″,2′′′-(1,2‑Phenylenebis[(1R,3R)-tetrahydro-5,8‑dioxo-1H-[1,2,4]diazaphospholo[1,2-a]pyridazine-2,1,3(3H)-triyl])tetrakis(N-[(1S)-1‑phenylethyl])benzamide[851609‑33‑1]C78H72N8O8P2FW 1311.40

685232-100MG 100 mg

685232-500MG 500 mg

sigma-aldrich.com

New Metal Precursors for Asymmetric Catalysis

Sigma-Aldrich® is pleased to offer a comprehensive portfolio of rhodium and iridium BARF complexes for asymmetric transformations.

B

F3C

F3C

F3C CF3

CF3

CF3

CF3F3C

Na

Sodium tetrakis[3,5-bis(trifl uoromethyl)phenyl]borate

692360

B

F3C

F3C

F3C CF3

CF3

CF3

CF3F3C

Rh

Bis(1,5-cyclooctadiene)rhodium(I)tetrakis[3,5-bis(trifl uoromethyl)-

phenyl]borate692573

B

F3C

F3C

F3C CF3

CF3

CF3

CF3F3C

Ir

Bis(cyclooctadiene)iridium(I) tetrakis(3,5-bis(trifl uoromethyl)-

phenyl)borate693774


Landis

Ligands













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Sigma-Aldrich® introduces Chem Product Central™, featuring the industry-leading range of 40,000+ products including cutting-edge catalysts and ligands, novel and classical synthetic reagents, and diverse libraries of building blocks. Chem Product Central™ uniquely categorized all chemical products by compound classes and application areas—making it easy to quickly fi nd what you need. Regular updates ensure that you have the most innovative products for your research.

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Aminophosphine Ligands

An increased interest in aminophosphine type ligands used forasymmetric synthesis has been witnessed. This growth in popularity ofaminophosphine ligands in asymmetric synthesis is in part due to thegrowing number of convenient synthetic pathways leading to usefulligand sets.1 Several groups have been using amino acids as precursors tosynthesize these ligands. Researchers at Kanata have synthesized severalsets of aminophosphine ligands showing great reactivity and selectivity ina wide array of enantioselective reactions.

Ruthenium Hydrogenation CatalystsA growing area of application for aminophosphine ligands inasymmetric synthesis is in ruthenium-catalyzed hydrogenations.2 Thisprocess is integral in the preparation of alcohols and amines, which areessential in the pharmaceutical, agrochemical, material, and finechemicals industries.

Chen et al. have described the use of ferrocenylaminophosphines in theruthenium-catalyzed asymmetric hydrogenation of acetonaphthone.2

Using precatalysts [RuCl2(benzene)]2 and the ferrocenyl basedaminophosphine ligand, they found that the hydrogenation proceededquickly with reasonable enantioselectivity (Scheme 1).Abdur-Rashid et al. reported the synthesis of cis-2-tert-butylcyclohexylalcohol using bis-2-(diphenylphosphino)ethylamine ruthenium dichlorideas a catalyst.3 Excellent selectivities were reported yielding only thecis-product (Scheme 2).

References: (1)(a) Abdur-Rashid, K. et al. J. Am. Chem. Soc. 2002, 124, 15104. (b) Abdur-Rashid, K. et al. J. Am. Chem. Soc. 2001, 123, 7473. (c) Guo, R. et al. J. Am. Chem. Soc.2005, 127, 516. (2) Chen, W.; Mbafor, W.; Roberts, S. M.; Whittall, J. Tetrahedron:Asymmetry 2006, 17,1161. (3) Abdur-Rashid, K. et al. Adv. Synth. Catal. 2005, 347, 571.

O HOFe PPh2

NH2

Ph

[Ru(benzene)Cl2]2

H2, t-BuOK, i-PrOH

100%, 66.7% ee

Scheme 1

ONH2

Ru

Ph2P

NH2

Ph2P

H2 / baseOH

100% cis

Cl

Cl

Scheme 2

2-(Di-tert-butylphosphino)ethylamine 8

C10H24NPFW 189.28

H3C

CH3

P

H3C CH3

NH2

CH3

H3C

JMR: 17-34 S: 26-36/37/39-45

697419-250MG 250 mg

2-(Diisopropylphosphino)ethylamine 8

C8H20NPFW 161.22

H3C

CH3

P

H3C CH3

NH2

LR: 36/37/38 S: 26

697427-250MG 250 mg

2-(Diphenylphosphino)ethylamine, ≥95.0% (GC)

(2-Aminoethyl)diphenylphosphine[4848‑43‑5]C14H16NPFW 229.26

PNH2

MR: 34 S: 26-36/37/39-45

43162-1G 1 g

2-(2-(Diphenylphosphino)ethyl)pyridine

[10150‑27‑3]C19H18NPFW 291.33 N P

695599-100MG 100 mg

(1S,2S)-(2-Amino-1-phenylpropyl)diphenylphosphine 8

(1S,2S)-(2-Diphenylphosphino)-1-methyl-2-phenylethyl-amineC21H22NPFW 319.38 P

CH3

NH2

LR: 36/37/38 S: 26

697583-100MG 100 mg

(1S,2S)-2-(Diphenylphosphino)-1,2-diphenylethyl-amine

8

C26H24NPFW 381.45

PNH2

LR: 36/37/38 S: 26

697389-100MG 100 mg


Aminophosp

hineLig

ands








(1S,2S)-(2-N-Methylamino-1-phenylpropyl)diphenyl-phosphine

8

(1S,2S)-N,1-Dimethyl-2-(diphenylphosphino)-2-phenyl-ethylamineC22H24NPFW 333.41 P

NH

CH3

CH3

697397-100MG 100 mg

2-[(11bS)-3H-Binaphtho[2,1-c:1′,2′-e]phosphepin-4(5H)-yl]ethanamine

8

C24H22NPFW 355.41

PNH2

697370-100MG 100 mg

(1S,2S)-1-((4R,11bS)-3H-Binaphtho[2,-c:1′,2′-e]phos-phepin-4(5H)-yl)-1-phenyl-2-propanamine

8

C31H28NPFW 445.53

P

H2NCH3

697362-100MG 100 mg

(1S,2S)-2-[(4R,11bS)-3H-dinaphtho[2,1-c:1′,2′-e]phos-phepin-4(5H)-yl]-1,2-diphenylethylamine

8

C36H30NPFW 507.60

P

H2N

JLR: 11-36/37/38 S: 26

696943-100MG 100 mg

(Rp)-1-[(1S)-(1-Aminoethyl)]-2-(diphenylphosphino)ferrocene

8

(Rp)-1-(1S)-[(2-Diphenylphosphino)-ferrocenyl]ethan-amine[607389‑84‑4]C24H24FeNPFW 413.27 Fe

CH3

NH2P

697354-100MG 100 mg

Dichlorobis[2-(di-tert-butylphosphino)ethylamine]ruthe-nium(II), 97%

C20H48Cl2N2P2RuFW 550.53

P

H2NP

NH2

RuCl

Cl

t-But-Bu

t-But-Bu

LR: 36/37/38 S: 26

664987-250MG 250 mg

664987-1G 1 g

Dichlorobis(2-(diphenylphosphino)ethylamine)ruthenium(II),95%

[506417‑41‑0]C28H32Cl2N2P2RuFW 630.49

P

H2NP

NH2

RuCl

Cl

PhPh

PhPh

LR: 36/37/38 S: 26

664979-250MG 250 mg

664979-1G 1 g

Chlorodihydrido[bis(2‑diisopropylphosphino)ethylamine]iri-dium(III), mixture of isomers, 97%

C16H39ClIrNP2FW 535.11

NH

P

P

IrCl

H

CH3H3CCH3

CH3

CH3

CH3

CH3

H3C

H

LR: 36/37/38 S: 26

664995-250MG 250 mg

664995-1G 1 g


Aminophosp

hineLigands

TrademarksThe following trademarks and registered trademarks are accurate to the best of our knowledge at the time of printing. Please consult individualmanufacturers and other sources for specific information.

AD-mix-α and AD-mix-β are sold under license from Rhodia Pharma Solutions.Air Products & Chemicals, Inc. — Selectfluor®

DSM — MonoPhos™MonoPhos™ family ligands are sold under license from DSM for research purposes only.Patent WO 0204466 applies.

Eppendorf-Netheler-Hinz GmbH — Eppendorf®

Evonik Degussa GmbH — catASium®

catASium® is sold in collaboration with Evonik Degussa GmbH for research purposes.GE Healthcare — Sepharose®

Imperial Chemical Industries Ltd. — Coomassie®

Johnson Matthey — BoPhoz™Kanata Chemical Technologies, Inc. — Ferrocelane™, RajPhos™Ferrocelane is sold in collaboration with Kanata Chemical Technologies, Inc.for research purposes only.

Nippon Chemical Industry Co., Ltd. — QuinoxP®

Sigma-Aldrich Biotechnology LP and Sigma-Aldrich Co. — ProteoSilver™,Sigma-Aldrich®

Solvias AG — Solvias®

Takasago Intl. Corp. — SEGPHOS®

SEGPHOS® is sold in collaboration with Takasago for research purposes only.












HPLC Chiral Column ScreeningHPLC chiral column screening protocol includes 3 mobile phase conditions run using 6 different chiral stationary phases. Positive separation is verifi ed on a separate system. Enantiomers are identifi ed as (+) and (-) using the Chiralyser optical rotation detection system.

GC Chiral Column ScreeningGC column screening involves exploration of 4 GC chiral phases. Samples that require derivatization are verifi ed by GC-MS.

HPLC and GC Chiral Method Optimization and Development ServicesTo establish the most effi cient method, an optimization study can be conducted as an outcome of the initial column screening. Method optimization may vary, depending on the intended use of the method. Some typical uses include:

• Isolation/purifi cation of enantiomers

• Resolution of metabolites

• Establishment of minimum detection limits

• LC-MS compatible methods for clinical, stability, or dissolution studies

Typical experiments in the optimization study include modifying buffer and pH, organic modifi er type and strength, and column temperature.

Small-Scale Enantiomeric Purifi cationIsolation of enantiomers is often required. The output of a small-scale purifi cation project can be milligram to gram quantities, depending on the needs of the client. Typical enantiomeric purity is 98% and verifi cation is determined by analytical methods established in the screening study.

Contact Technical Service to discuss your chiral project needs.Email: [email protected]: 800-359-3041

Chiral column screening, method optimization and small-scale enantiomeric purifi cation services

Chiral Analytical Services

Pricing, Turnaround Time and DeliverablesHPLC and GC chiral column screening is typically completed within 3 working days. A full report is supplied and a column is recommended upon completion of the project. A charge for the service is incurred whether or not a separation is identifi ed. At that time, optimization, method development, and purifi cation studies can be initiated if desired by the client.

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Supelcoadsized_ed.indd 1Supelcoadsized_ed.indd 1 5/7/2008 8:47:23 AM5/7/2008 8:47:23 AM


TO ORDER: Contact your local Sigma-Aldrich office (see back cover), or visit sigma-aldrich.com/chemicalsynthesis.90 sigma-aldrich.com

Risk PhrasesINDICATION OF PARTICULAR RISKS: R1: Explosive when dry 2: Risk of explosion by shock, friction, fire or other sources of

ignition 3: Extreme risk of explosion by shock, friction, fire or other

sources of ignition 4: Forms very sensitive explosive metallic compounds 5: Heating may cause an explosion 6: Explosive with or without contact with air 7: May cause fire 8: Contact with combustible material may cause fire 9: Explosive when mixed with combustible material 10: Flammable 11: Highly flammable 12: Extremely flammable 14: Reacts violently with water 15: Contact with water liberates extremely flammable gases 16: Explosive when mixed with oxidizing substances 17: Spontaneously flammable in air 18: In use may form flammable/explosive vapor-air mixture 19: May form explosive peroxides 20: Harmful by inhalation 21: Harmful in contact with skin 22: Harmful if swallowed 23: Toxic by inhalation 24: Toxic in contact with skin 25: Toxic if swallowed 26: Very toxic by inhalation 27: Very toxic in contact with skin 28: Very toxic if swallowed 29: Contact with water liberates toxic gas 30: Can become highly flammable in use 31: Contact with acids liberates toxic gas 32: Contact with acids liberates very toxic gas 33: Danger of cumulative effects 34: Causes burns 35: Causes severe burns 36: Irritating to the eyes 37: Irritating to the respiratory system 38: Irritating to the skin 39: Danger of very serious irreversible effects 40: Limited evidence of a carcinogenic effect 41: Risk of serious damage to eyes 42: May cause sensitization by inhalation 43: May cause sensitization by skin contact 44: Risk of explosion if heated under confinement 45: May cause cancer 46: May cause heritable genetic damage 48: Danger of serious damage to health by prolonged exposure 49: May cause cancer by inhalation 50: Very toxic to aquatic organisms 51: Toxic to aquatic organisms 52: Harmful to aquatic organisms 53: May cause long-term adverse effects in the aquatic environ-

ment 54: Toxic to flora 55: Toxic to fauna 56: Toxic to soil organisms 57: Toxic to bees 58: May cause long-term adverse effects in the environment 59: Dangerous for the ozone layer 60: May impair fertility 61: May cause harm to the unborn child 62: Possible risk of impaired fertility 63: Possible risk of harm to the unborn child 64: May cause harm to breast-fed babies 65: Harmful: may cause lung damage if swallowed 66: Repeated exposure may cause skin dryness or cracking 67: Vapors may cause drowsiness and dizziness 68: Possible risk of irreversible effects

COMBINATION OF PARTICULAR RISKS: 14/15: Reacts violently with water, liberating extremely flammable

gases 15/29: Contact with water liberates toxic, extremely flammable gas 20/21: Harmful by inhalation and in contact with skin 20/21/22: Harmful by inhalation, in contact with skin and if swallowed 20/22: Harmful by inhalation and if swallowed 21/22: Harmful in contact with skin and if swallowed 23/24: Toxic by inhalation and in contact with skin 23/24/25: Toxic by inhalation, in contact with skin and if swallowed 23/25: Toxic by inhalation and if swallowed 24/25: Toxic in contact with skin and if swallowed 26/27: Very toxic by inhalation and in contact with skin 26/27/28: Very toxic by inhalation, in contact with skin and if swal-

lowed 26/28: Very toxic by inhalation and if swallowed 27/28: Very toxic in contact with skin and if swallowed 36/37: Irritating to eyes and respiratory system 36/37/38: Irritating to eyes, respiratory system and skin 36/38: Irritating to eyes and skin 37/38: Irritating to respiratory system and skin 39/23: Toxic: danger of very serious irreversible effects through inha-

lation 39/23/24: Toxic: danger of very serious irreversible effects through inha-

lation and in contact with skin 39/23/24/25: Toxic: danger of very serious irreversible effects through inha-

lation, in contact with skin and if swallowed 39/23/25: Toxic: danger of very serious irreversible effects through inha-

lation and if swallowed 39/24: Toxic: danger of very serious irreversible effects in contact

with skin 39/24/25: Toxic: danger of very serious irreversible effects in contact

with skin and if swallowed 39/25: Toxic: danger of very serious irreversible effects if swallowed 39/26: Very toxic: danger of very serious irreversible effects through

inhalation 39/26/27: Very toxic: danger of very serious irreversible effects through

inhalation and in contact with skin 39/26/27/28: Very toxic: danger of very serious irreversible effects through

inhalation, in contact with skin and if swallowed 39/26/28: Very toxic: danger of very serious irreversible effects through

inhalation and if swallowed 39/27: Very toxic: danger of very serious irreversible effects in contact

with skin 39/27/28: Very toxic: danger of very serious irreversible effects in con-

tact with skin and if swallowed 39/28: Very toxic: danger of very serious irreversible effects if swal-

lowed 42/43: May cause sensitization by inhalation and skin contact 48/20: Harmful: danger of serious damage to health by prolonged

exposure through inhalation 48/20/21: Harmful: danger of serious damage to health by prolonged

exposure through inhalation and in contact with skin 48/20/21/22: Harmful: danger of serious damage to health by prolonged

exposure through inhalation, in contact with skin and if swallowed

48/20/22: Harmful: danger of serious damage to health by prolonged exposure through inhalation and if swallowed

48/21: Harmful: danger of serious damage to health by prolonged exposure in contact with skin

48/21/22: Harmful: danger of serious damage to health by prolonged exposure in contact with skin and if swallowed

48/22: Harmful: danger of serious damage to health by prolonged exposure if swallowed

48/23: Toxic: danger of serious damage to health by prolonged exposure through inhalation

48/23/24: Toxic: danger of serious damage to health by prolonged exposure through inhalation and in contact with skin

48/23/24/25: Toxic: danger of serious damage to health by prolonged exposure through inhalation, in contact with skin and if swallowed

48/23/25: Toxic: danger of serious damage to health by prolonged exposure through inhalation and if swallowed

48/24: Toxic: danger of serious damage to health by prolonged exposure in contact with skin

48/24/25: Toxic: danger of serious damage to health by prolonged exposure in contact with skin and if swallowed

48/25: Toxic: danger of serious damage to health by prolonged exposure if swallowed

Ris

k &

Saf

ety

CFVol8No2FINAL.indd Sec1:90CFVol8No2FINAL.indd Sec1:90 5/15/2008 10:45:12 AM5/15/2008 10:45:12 AM


50/53: Very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment

51/53: Toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment

52/53: Harmful to aquatic organisms, may cause long-term adverse effects in the aquatic environment

68/20: Harmful: possible risk of irreversible effects through inhala-tion

68/20/21: Harmful: possible risk of irreversible effects through inhala-tion and in contact with skin

68/20/21/22: Harmful: possible risk of irreversible effects through inhala-tion, in contact with skin and if swallowed

68/20/22: Harmful: possible risk of irreversible effects through inhala-tion and if swallowed

68/22: Harmful: possible risk of irreversible effects if swallowed 68/21: Harmful: possible risk of irreversible effects in contact with

skin 68/21/22: Harmful: possible risk of irreversible effects in contact with

skin and if swallowed

Safety PhrasesINDICATION OF SAFETY PRECAUTIONS: S1: Keep locked up 2: Keep out of the reach of children 3: Keep in a cool place 4: Keep away from living quarters 5: Keep contents under ... (appropriate liquid to be specified

by the manufacturer) 6: Keep under ... (inert gas to be specified by the manufac-

turer) 7: Keep container tightly closed 8: Keep container dry 9: Keep container in a well-ventilated place 12: Do not keep the container sealed 13: Keep away from food, drink and animal feeding stuffs 14: Keep away from ... (incompatible materials to be indicated

by the manufacturer) 15: Keep away from heat 16: Keep away from sources of ignition - No smoking 17: Keep away from combustible material 18: Handle and open container with care 20: When using, do not eat or drink 21: When using, do not smoke 22: Do not breathe dust 23: Do not breathe gas/fumes/vapor/spray (appropriate wording

to be specified by the manufacturer) 24: Avoid contact with skin 25: Avoid contact with eyes 26: In case of contact with eyes, rinse immediately with plenty

of water and seek medical advice 27: Take off immediately all contaminated clothing 28: After contact with skin, wash immediately with plenty of ...

(to be specified by the manufacturer) 29: Do not empty into drains 30: Never add water to this product 33: Take precautionary measures against static discharges 35: This material and its container must be disposed of in a safe

way 36: Wear suitable protective clothing 37: Wear suitable gloves 38: In case of insufficient ventilation, wear suitable respiratory

equipment 39: Wear eye/face protection 40: To clean the floor and all objects contaminated by this mate-

rial use ... (to be specified by the manufacturer) 41: I n case of fire and/or explosion do not breathe fumes

42: During fumigation/spraying wear suitable respiratory equip-ment (appropriate wording to be specified by the manufac-turer)

43: In case of fire, use ... (indicate in the space the precise type of fire-fighting equipment. If water increases the risk add - Never use water)

45: In case of accident or if you feel unwell, seek medical advice immediately (show label where possible)

46: If swallowed, seek medical advice immediately and show this container or label

47: Keep at temperature not exceeding ... ºC (to be specified by the manufacturer)

48: Keep wet with ... (appropriate material to be specified by the manufacturer)

49: Keep only in the original container 50: Do not mix with ... (to be specified by the manufacturer) 51: Use only in well-ventilated areas 52: Not recommended for interior use on large surface areas 53: Avoid exposure - obtain special instruction before use 56: Dispose of this material and its container to hazardous or

special waste collection point 57: Use appropriate container to avoid environ mental contami-

nation 59: Refer to manufacturer/supplier for information on recovery/

recycling 60: This material and/or its container must be disposed of as

hazardous waste 61: Avoid release to the environment. Refer to special instruc-

tions/safety data sheet 62: If swallowed, do not induce vomiting: seek medical advice

immediately and show this container or label 63: In case of accident by inhalation, remove casualty to fresh air

and keep at rest 64: If swallowed, rinse mouth with water (only if the person is

conscious)

COMBINATION OF SAFETY PRECAUTIONS: 1/2: Keep locked up and out of the reach of children 3/7: Keep container tightly closed in a cool place 3/9/14: Keep in a cool well-ventilated place away from ... (incompat-

ible materials to be indicated by manufacturer) 3/9/14/49: Keep only in the original container in a cool well-ventilated

place away from ... (incompatible materials to be indicated by manufacturer)

3/9/49: Keep only in the original container in a cool well-ventilated place

3/14: Keep in a cool place away from ... (incompatible materials to be indicated by the manufacturer)

7/8: Keep container tightly closed and dry 7/9: Keep container tightly closed and in a well-ventilated place 7/47: Keep container tightly closed and at a temperature not

exceeding ... ºC (to be specified by manufacturer) 20/21: When using, do not eat, drink or smoke 24/25: Avoid contact with skin and eyes 27/28: After contact with skin, take off immediately all contami-

nated clothing and wash immediately with plenty of ... (to be specified by the manufacturer)

29/35: Do not empty into drains, dispose of this material and its container in a safe way

29/56: Do not empty into drains, dispose of this material and its container at hazardous or special waste-collection point

36/37: Wear suitable protective clothing and gloves 36/37/39: Wear suitable protective clothing, gloves and eye/face pro-

tection 36/39: Wear suitable protective clothing and eye/face protection 37/39: Wear suitable gloves and eye/face protection 47/49: Keep only in the original container at temperature not

exceeding ... ºC (to be specified by manufacturer)

GExplosive

E HOxidizing

O JHighly Flammable

or Extremely Flammable

FF+ L

Harmful or Irritant

XnXi M

Corrosive

C IBiohazard

B QDangerous for the

Environment

NKToxic or

Very Toxic

TT+ R

Radioactive

R

PictogramsPictograms are based on widely accepted standards.

Risk &

Safety


KKZ03867-5047400058

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asymmetric catalysis, privileged ligands and complexes · asymmetric catalysis privileged ligands...

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