anion binding in catalysis - princeton university · chiral anion mediated asymmetric chemistry!...

Anion binding in Catalysis

Asymmetric and Non-Asymmetric Examples

Andy McNally

MacMillan Group Meeting

2/04/09

Chiral Anion Mediated Chemistry

! The use of 'cationic' counter-ion chemsitry far outweighs anion-binding

Introduction

SubstrateCounter-ion

!+ !–

SubstrateCounter-ion

!– !+

vs

! Ion-pair catalysis has been known for a very long time - phase transfer catalysis

! Ion-pairing involving a catalytic anionic component has only recently emerged

! New strategy for catalysis:

! Unexplored reactivity

! Enhanced reactivity vs ligand based approaches

! New asymmetric variants and entirely new transformations

Chiral Anion Mediated Asymmetric Chemistry

! The chiral pool provides a convenient source of enantiomerically pure anions

From Humble Beginings to New Strategies for Catalysis

–O2CCO2

–

OH

OH

Ph CO2–

OH

–O2CCO2

–

OCOPh

OCOPh

Me Me

OSO3

–

O

O

O

O

O

O

Sb

SbO

O

O

O

O

O

2–

Me Me

O

O

F3C

Eu

4

–

Review: Lacour, J. Chem. Soc. Rev. 2003, 32, 373-382.

Cl O

O

B

ClO

O

O

O

B

O

O

Me Me

MeMe

O

O

B

O

O

Me Me

O

OB

O

O

R

R

O

OB

O

OBB

O

O

P

O

O

O

O

P

O

O

O

O

Cl

Cl

Cl

Cl

Cl

ClCl

Cl

O

P

O

O

O

O

Cl

Cl

Cl

Cl

Cl

ClCl

Cl

O

Cl

Cl

Cl

Cl


! Uses of chira anions: determination of enantiomeric purity


N

N

Me

Me

Me

Me

Me

Me

NMe3

Me P

MeO

CD3

CH3

Mn(CO3

OMe

Me

S

Pht-Bu

Me

O

O

P

OO

OO

Cl

Cl

Cl

Cl

Cl

ClCl

Cl



! Uses of chira anions: purification and enantiomeric separation of cations


O

P

OO

OO

Cl

Cl

Cl

Cl

Cl

ClCl

Cl

O

Cl

Cl

Cl

Cl

N N

Me

Me

Me

Me

X

(X = H or NMe2)

MeO OMe

O

Me

O

Me

MeO OMe N N

X

(X = H or Br)



! First transition metal-catalysed enantioselective transformation using chiral anions


PhPhINTs

TsN

Ph

O

OB

O

OCu(MeCN)4

Benzene

Arndstsen, B. A. Org. Lett. 2000, 2, 4165-4168.


! Aziridination under 'classical' conditions displays a pronounced counteranion effect


PhPhINTs

TsN

Ph

10 mol% CuX, 0 ºC N

O

N

O

Me Me

t-Bu t-Bu

(11 mol%)

X % ee (benzene) % ee (MeCN)

OTf 66 2

ClO4 57 2

Cl 26 2

PF6 33 2



! Synthesis of copper-boronate catalyst


O

OB

O

O

Cu(MeCN)4

OH

OH

1) H2BBrSMe2

2) Ag2CO3

Ag

O

OB

O

O

CuCl

MeCN



! Ion-pair crystal structure


Cu-O, 2.16 A


! Enantiocontrol from chiral boronate is low


PhPhINTs

TsN

Ph

O

OB

O

OCu(MeCN)4

(1-3 mol% Cu-B(OR*)4)

1-3 mol% L

N

O

N

O

Me Me

t-Bu t-Bu

(S)-Cu-B(OR*)4

13% ee (R)

N

O

N

O

Me Me

t-Bu t-Bu

(R)-Cu-B(OR*)4

12% ee (R)

no ligand

(S)-Cu-B(OR*)4

7% ee (S)

no ligand

(R)-Cu-B(OR*)4

7% ee (R)

(R)-Cu-B(OR*)4

NN

10% ee (R)


Cu-O, 2.55A


! Crystal structure of (bipy)Cu(H2C=CHPh)+(R)-B(OR*)4–



! Peptide derived chiral boranate cannot provide useful levels of enantioselectivity


Ph Ph

Cu(MeCN)

1 mol%, CH2Cl2N2

O

OEt

O

B

O

O

O

NH

O

CO2Me

Me

Me

NH

O

CO2Me

Me

Me

HN

O

HN

O

CO2Me

CO2Me

Me

Me

Me

Me

CO2Et

Ph

CO2Et

max ee's 19% 34%

1:1 dr 3% yield

Arndstsen, B. A. Tetrahedron: Asymmetry 2005, 16, 1789-1799.

Braun, M. Angew. Chem. Intl. Ed 2004, 43, 514-517.

Titanium (IV) Catalysed Allylation

! Braun allylation of ethers is an overlooked reaction within this class

Anion Binding With Useful Levels of Selectivity

Me OTMS TMS Ti-cat. 10 mol%

–TMSOTMS

Me

96% 98.9% ee

Me OTMS(±)

Me

Me3SiOTiL*F2

Me

Me3SiOTiL*F2

ON

OPh

Ph

Ph

TiF2

t-Bu

t-Bu

Me

(S)

Me

(R)

Substrate

Gold Mediated Counteranion Catalysis

! Gold Catalysed enantioselective transformations were predicted to be difficult

The Toste Story

Au+Ligand

Large Distance

Short Reviews: Krause. Angew. Chem. Intl. Ed. 2008, 47, 2178-2181; Widenhoefer. Chem. Eur. J. 2008, 14, 5382-5391.


! Solution one: Development of bis(gold)-phosphine complexes

The Toste Story

O

O

O

O P

P

Au

Cl

Au

Cl

t-Bu

OMe

t-Bu

t-Bu

OMe

t-Bu

2

2

P

P

Au

Cl

Au

Cl

t-Bu

OMe

t-Bu

t-Bu

OMe

t-Bu

2

2

MeO

MeO

(R)-DTBM-SEGPHOS-(AuCl)2

(S)-DTBM-MeOBIPHEP-(AuCl)2

OPiv

Me Me

Ar Ar

Me

Me

PivO

2.5 mol% cat.

5 mol % AgSbF6

2.5 mol% cat.

5 mol % AgSbF6

2.5 mol% cat.

5 mol % AgSbF6

OH

PhPh n

O

PhPh

*

n = 0, 67%, 93% een = 1, 96%, 88% ee

TsN

Me

Me

NHTs Me

Me

99%, 99% ee

60-85%

76-94% ee

Substrate


! Chiral anion strategy may also overcome inherent proximity problem

The Toste Story

Au+Ligand

Large Distance

Counter-ion ShortDistance

Toste, D. F. J. Am. Chem. Soc. 2007, 129, 2452-2453.


! Counter-ion effects had already been identified in ligand controlled reactions

The Toste Story

P

P

Au

Cl

Au

Cl

2

2

(R)-xylyl-BINAP-(AuCl)2

TsNNHTs

Me

Me

Me

Me

P Au Cl

P Au Cl

*

P Au Cl

P Au

*

+ BF4–

P Au

P Au

*

2+ 2BF4–

3 mol% cat, 3 mol% AgBF4

81% 51% ee

3 mol% cat, 6 mol% AgBF4

82% 1% ee

Toste, D. F. Science 2007, 317, 496-499


! Initial investigations: ligand vs anion control

The Toste Story

PR2

PR2

OOH H3 mol% L(AuCl)2, 3 mol% AgX

PR2

PR2

O

O

O

O

AgBF4

Ag-CO2-4-(NO2)-C6H3

0-8% ee

CH2Cl2

Toste, D. F. Science 2007, 317, 496-499



The Toste Story

OOH HLAuCl or L(AuCl)2, AgCat

L = PPh3 (5 mol%), 5 mol% (R)-Agcat

L = dppm (2.5 mol%), 5 mol% (R)-Agcat

CH2Cl2

O

OP

OAg

O

i-Pr i-Pr

i-Pr

i-Pr

i-Pri-Pr

L = dppm (2.5 mol%), 5 mol% (R)-Agcat

89% 48% ee

76% 65% ee

90% 98% ee

(benzene)

dppm = Ph2P PPh2

Toste, D. F. Science 2007, 317, 496-499



The Toste Story

O

R1

R1

R1

R1

OH H2.5 mol% dppm(AuCl)2

benzene, 23 ˚C

n

R2 R2

R3 R3

R3

R3

R2R2

n

79-96% 90-99% ee

5 mol% Agcat.

SO2MesN

R1

R1

R1

R1

NHSO2Mes H5 mol% Ph(CH3)2PAuCl

benzene, 23 ˚C

R2 R2

R2R2

73-97% 96-99% ee

5 mol% Agcat.

Toste, D. F. Science 2007, 317, 496-499

Substrate


! Chiral amplification via ligand-counter ion relay

The Toste Story

Au+Ligand

Large Distance

Counter-ion ShortDistance

Toste, D. F. Science 2007, 317, 496-499

Substrate


! Chiral amplification via ligand-counter ion relay

The Toste Story

Au+Ligand

Large Distance

Counter-ionInteraction

ChiralAmplification?

Toste, D. F. Science 2007, 317, 496-499


! Chiral amplification vis ligand-counterion relay

The Toste Story

benzene, 23 ˚C

5 mol% Agcat.OH OH

O

OP

OAg

O

i-Pr i-Pr

i-Pr

i-Pr

i-Pri-Pr

Ph2P PPh2

dppm

2.5 mol% dppm(AuCl)2

96% 80% ee



The Toste Story

benzene, 23 ˚C

5 mol% Agcat.OH OH

O

OP

OAg

O

i-Pr i-Pr

i-Pr

i-Pr

i-Pri-Pr

P

(S,S)-DIPAMP

2.5 mol% [(S,S)-DIPAMP](AuCl)2

96% 92% ee

P

Ph

PhMeO

OMe

Toste, D. F. Science 2007, 317, 496-499

Toste, D. F. Science 2007, 317, 496-499



The Toste Story

OH

benzene, 23 ˚C

5 mol% Agcat.

O

OP

OAg

O

i-Pr i-Pr

i-Pr

i-Pr

i-Pri-Pr BINAP

dppm (R)-AgCat.

Me

MeO

O OMe

Me

H5 mol% L(AuCl)2

(R)-BINAP (R)-AgCat.

(S)-BINAP (R)-AgCat.

PPh2

PPh2

89% 12% ee (S)

91% 3% ee (R)

88% 82% ee (S)

Norton, J. R. J. Am. Chem. Soc. 2005, 127, 7805-7814

Chiral Couneranion-Aided Asymmetric Hydrogenation

! Imine hydrogenation via an ionic mechanism

Asymmetric Imine Reduction

N

R'R

M–H N

R'RH

M

M+

N

R'R

M–H

N

R'RH

H2

MH

H

N

R'RH

N

R'RH

H

Norton, J. R. J. Am. Chem. Soc. 2005, 127, 7805-7814


! Imine hydrogenation via an ionic mechanism


N

R'R

M–H N

R'RH

M

M+

N

R'R

M–H

N

R'RH

H2

MH

H

N

R'RH

N

R'RH

H

N

Me

BF4–

N

MeH

2 mol %

CpRu(P-P)HPPh2

PPh2

(R,R)-Norphos50 psi H2

74% 54% ee

Xiao, J. J. Am. Chem. Soc. 2008, 130, 14450-14451


! Ir(III)-Phosphoric acid system leads to high enantioselectivities via ligand-anion control


NR1

R3R2L

M

L

X*–

H2*

L

M

L* H

NR1

R3R2

HX*–

HNR1

R3R2




NR1

R3R2L

M

L

X*–

H2*

L

M

L* H

NR1

R3R2

HX*–

HNR1

R3R2

N

Me

OMe

[Ir] (1mol%)

H2 (20 bar), toluene, 20 ºC

HN

Me

OMe

Ph

Ph

N

NH

Ir

ArO2S

0% 0% ee

Ph

Ph

N

NH

Ir

ArO2S

30% 81% ee

Ph

Ph

N

NH

Ir

ArO2S

27% –3% ee

O

OP

O

OH

R

R

(R = 2,4,6-(2-C3H7)3C6H2)

Pacid (6mol%)

(Ar = 4-CH3C6H4)






NR1

R3R2L

M

L

X*–

H2*

L

M

L* H

NR1

R3R2

HX*–

HNR1

R3R2

N

Me

OMe

[Ir] (1mol%)


HN

Me

OMe

Ph

Ph

N

NH2

Ir

ArO2S

76% 97% ee 92% 97% ee

O

OP

O

OH

R

R

(R = 2,4,6-(2-C3H7)3C6H2)

Pacid (x mol%)

(Ar = 2,3,4,5,6-(CH3)5C6)

O

PO

OR*

OR*

Ph

Ph

N

NH2

Ir

ArO2S

O

PO

OR*

OR*

+ 1 mol%Pacid





N

Me

R1


HN

Me

R1

92-95% 84-97% ee

O

OP

O

OH

R

R

(R = 2,4,6-(2-C3H7)3C6H2)

(Ar = 2,3,4,5,6-(CH3)5C6)

Ph

Ph

N

NH2

Ir

ArO2S

O

PO

OR*

OR*

+ 1 mol%Pacid

R2 R2

NHPMB

MeNHPMB

Me

NHPMB

MeMe

Me NHPMB

MeMe

93% 91% ee 88% 95% ee

90% 92% ee 91% 94% ee

List, B. J. Am. Chem. Soc. 2007, 129, 11336-11337.

Chiral Counteranions in Transition Metal Catalysis

! Pd/Brønsted acid-catalysed direct allylation of aldehydes

Chiral Co-Catalysts - List

O

OP

O

OH

i-Pr

i-Pr i-Pr

i-Pr

i-Pr i-Pr(1.5 mol%)

5A MS, MTBE, 40 ºC, 8-24 hr

O

R1 = Ar: 40-89% 83-97% ee

Me

R1

O

MeR1

R2

Ph

NH

Ph R2

(1.0 equiv)

Pd(PPh3)4 3 mol%

˚

R1 = Alkyl: 45-65% 80-90%ee

Iminium Catalysis - An Alternative Approach

! Proposed mechanism


O

MeH2O

NH

R

(R)-TRIP

R1

N

HR

R1Me

O

P

OR*O OR*

N

Me

R1

H R

P

O

OR**RO

O

Pd

Pd(0)

N

R1

Me

R

H

O

P

OR*O*RO

O

Me R1

(R)-TRIP


Chiral Anion Phase Transfer Catalysis

! Reverse of roles commonly associated in phase transfer systems

Chiral Borate Anions

R

R N

Cl

(±)

R

R

N

X–

R

R N

NucAnion cat. Nuc

O

O

B

O

O

Et3NH+

i-Pr i-Pr

i-Pr i-Pr

O

OP

O

OAg

i-Pr

i-Pr

2008 - Toste >90% ee2003 - Nelson <15% ee

ASYMMETRIC RING OPENING OF MESO-AZIRIDINIUM IONS




Ph

Ph N

Cl

(±)

Ph

Ph

N

*B(OR)4–

Ph

Ph N

HN

50 mol% cat.

O

O

B

O

O

A+


THF-Toluene100 ˚C

H2N PhPh

A+ Yield % ee %

Et3NH+

Et2NH2+

Ph NH3+

Me

(R)

Na+

25%

18%

12%

30%

15%

–6%

–7%

3% (R, R)

8% (S, S)

Nelson, A. Tetrahedron: Asymmetry 2003, 14, 1995-204.


! Ion-pairing NMR studies


O

O

B

O

O

Nelson, A. Tetrahedron: Asymmetry 2003, 14, 1995-204.

N

Ph NH3+

Me

OTf

! Borate salt was found to be soluabalised but the aziridinium triflate in CDCl3

! Proton and carbon shifts vary linearly with amount of borate salt present

! Lack of spliting of enatiotopic protons in the aziridium salt indicates poor discrimination from the chiral anion

HA

HA

HB

HB

HC

HC



Chiral Phosphonate Anions

R

R N

Cl

(±)

R

R

N

X–

R

R N

NucAnion cat. Nuc

O

O

B

O

O

Et3NH+

i-Pr i-Pr

i-Pr i-Pr

O

OP

O

OAg

i-Pr

i-Pr

2008 - Toste >90% ee2003 - Nelson <15% ee



! Halide abstraction method requires regeneration of chiral silver salt


Ph

Ph N

Cl

(±)

Ph

Ph

N

Cat.–

Ph

Ph N

NucCat.Ag Nuc


–AgCl –Cat.H

! Addition of an achiral Ag(I) source must not introduce an interfereing counteranion

R-Hal

AgHalAgB

BH

NucHR-Nuc

AgCat.

R+ Cat.–HCat.

Halide

Abstraction




Ph

Ph N

Cl

(±)

Ph

Ph

N

Cat.–

Ph

Ph N

NucCat.Ag Nuc


–AgCl –Cat.H


R-Hal

AgHalAgB

BH

NucHR-Nuc

AgCat.

R+ Cat.–HCat.

Nucleophilic Addition




Ph

Ph N

Cl

(±)

Ph

Ph

N

Cat.–

Ph

Ph N

NucCat.Ag Nuc


–AgCl –Cat.H


R-Hal

AgHalAgB

BH

NucHR-Nuc

AgCat.

R+ Cat.–HCat.

PhaseTransfer

Use solid phase Ag(I)

solid-liquid PTC

Toste, F. D. J. Am. Chem. Soc. 2008, 130, 14984-14986.


! Suitability of silver(I) sources is crucial for the catalyst control


Ph

Ph N

Cl

(±)

Ph

Ph

N

Cat.–

Ph

Ph N

O15 mol% cat.

i-Pr i-Pr

i-Pr i-Pr

O

OP

O

OAg

i-Pr

i-Pr


HO

Me

MeMe

Toluene, 50˚C

AgB

AgOTs

Ag2CO3

Ag2CO3

88% 56% ee

77% 94% ee

84% 94% ee(4A MS)

Me

MeMe

–

–

–



! Utility - alcohol and amine fucntionality


81% 92% ee

Ph

Ph N

O Me

Me OMe

Ph

Ph N

O

Me Me

OTBS

Ph

Ph N

O

OO

Ph

Ph N

O

MeMeMe

Ph

Ph N

O Me

Me OMe

Me

Me

Ph

Ph N

O Me

Me OMe

N

O

4-NO2-Ph

Ph

Ph N

OPh

Ph N

O Me

Me OMe

Me

67% 94% ee 85% 97% ee 50% 92% ee

86% 92% ee 70% 99% ee 76% 94% ee 80% 94% ee, 94% de


! Extention to meso-episulfonium ions uses a modified system


Ph

Ph SMe

O

(±)

Ph

Ph

SMe

Cat.–

Ph

Ph SMe

OR15 mol% cat.

i-Pr i-Pr

i-Pr i-Pr

O

OP

O

OH

i-Pr

i-Pr

ASYMMETRIC RING OPENING OF MESO-EPISULFONIUM IONS

ROH

Toluene, 23˚C

90-98% yield

CCl3HN

87-92%ee

! Mechanistically distinct from other phosphoric acid catalysed reactions enantioselectivity results from H-bonding to the electrohile

! Ring opening of the meso-episulfonium is the enantiodetermining step. Ion-pairing is responsible for the stereoselectivity


Hydrogen Bonding Mediated Counterion Catalysis

! Ureas and thioureas are proven motifs towards anion-binding using hydrogen bonding

Anion Recognition

Review: Schmidtchen, F. P. Chem. Rev. 1997, 97, 1609-1646.


! The stereoselectivity achieved by thiourea catalysts appears unusual

The Jacobsen Story

NH

NH2

RO

R'H

1) R'CHO, 3A MS˚

2) AcCl, 2,6-lutidine

Cat. (5-10 mol%)

Et2O, –30 to –60 ºC

NH

RNAc

R'

65-81%, 85-95%ee


! The stereoselectivity achieved by thiourea catalysts appears unusual

The Jacobsen Story

NH

NH2

RO

R'H

NH

RN

R'

1) R'CHO, 3A MS˚

2) AcCl, 2,6-lutidine

Cat. (5-10 mol%)

Et2O, –30 to –60 ºC

Me

O

Cl

N

N

S

t-Bu

N(i-Bu)2

O

N

Ph

Ph

H

H

NH

RNAc

R'

65-81%, 85-95%ee

! "The ability to activate a weakly Lewis basic N-acyliminium ion towards enantioselective transformations presents new opportunities for catalysis and raises intriguing questions as to the nature of this interaction."

Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126, 10558-10559.


! H-Bond donor - anion binding catalysis is proposed in 2007

The Jacobsen Story

Cat. (10 mol%)

–55 ºC or –78 ºC

52-94%, 81-99%ee

! Alkylated derivatives react significantly faster than reduced compounds. SN1 mechanism.

NH

N

O

R4

HO

R1

R2

R3 n=1, 2NH

R1

R2

R3

N O

R4n=1, 2

TMSCl, TBME

! SN2 Mechanism

NH

N

O

RCl N

H

N O

R

Jacobsen, E. N. J. Am. Chem. Soc. 2008, 127, 13404-13405..


! Two SN1-type mechanisms are likely

The Jacobsen Story

NH

N

O

RCl N

H

N O

RNH

N

O

R

Cl–

N

N

H

S

N

H

t-Bu

R

PhMe

N

N

O

Cl–N

H

S NH

R1

R2

R

spiro pathway

direct pathway



The Jacobsen Story

NH

N

O

RCl N

H

N O

RNH

N

O

R

Cl–

N

N

H

S

N

H

t-Bu

R

PhMe

N

N

O

Cl–N

H

S NH

R1

R2

R

spiro pathway

direct pathway

! DFT calculations of fully ionised N-acyliminium ions interacting with thiourea derivatives failed to converge on any ground state structure.



The Jacobsen Story

NH

N

O

RCl N

H

N O

RNH

N

O

R

Cl–

N

N

H

S

N

H

t-Bu

R

PhMe

N

N

O

Cl–N

H

S NH

R1

R2

R

spiro pathway

direct pathway

! Pronounced counter ion effect:

X– ee

Cl– 97%

Br– 68%

I– <5%



The Jacobsen Story

NH

N

O

RCl N

H

N O

RNH

N

O

R

Cl–

N

N

H

S

N

H

t-Bu

R

PhMe

N

N

O

Cl–N

H

S NH

R1

R2

R

spiro pathway

direct pathway

! Pronounced solvent effect

solv ee

TBDME 97%

THF 34%

DCM <5%

see also: Jacobsen, E. N. Org. Lett,2008, 10,1577-1578.


! A versatile method for other highly reactive cationic species?

The Jacobsen Story

Cl–

N

N

H

S

N

H

t-Bu

R

PhMe

R3N

O

R4

R1 R2

Cl–

N

N

H

S

N

H

t-Bu

R

PhMe

O

Nuc

Nuc

ACYL-IMINIUM ION STABILISATION OXOCARBENIUM ION STABILISATION?


! A versatile method for other highly reactive cationic species?

The Jacobsen Story

Cl–

N

N

H

S

N

H

t-Bu

R

PhMe

R3N

O

R4

R1 R2

Cl–

N

N

H

S

N

H

t-Bu

R

PhMe

O

Nuc

Nuc

ACYL-IMINIUM ION STABILISATION OXOCARBENIUM ION STABILISATION?

! Cyclic oxo-carbenium ions are extremely unstable species (lifetime ~ 10-12 s)

! Enantioselective addtions to oxo-carbenium ions are extememly rare with only two examples reported (Braun: Angew. Intl. Ed. 2004, 43, 514-517 and Evans: JACS, 2005, 127, 10506-10507).


! Importance of catalyst structure

The Jacobsen Story

10 mol% cat.

ENANTIOSELECTIVE ADDITIONS TO OXOCARBENIUM IONS

TBDME, –78 ˚CO

Cl

R

OSIR3

OR1

R2

R2

OR

R2 CO2R1R2

70-96% 74-97%ee

NH

NH

St-Bu

N

O

F

CF3

CF3

Reactivity at low temp

3º amide important forreactivity and selectivity

Aryl group crucial forselectivity - engagesoxocarbenium ion in TS?

Jacobsen, E. N. J. Am. Chem. Soc. 2008, 130 ,7198-7199.



The Jacobsen Story

10 mol% cat.


TBDME, –78 ˚CO

Cl

R

OSIR3

OR1

R2

R2

OR

R2 CO2R1R2

70-96% 74-97%ee

O

CO2Me

O

CO2Me

O

CO2Me

O

CO2Me

Me

F MeO

87% 87% ee 71% 90% ee 70% 90% ee 96% 74% ee




The Jacobsen Story

10 mol% cat.


TBDME, –78 ˚CO

Cl

R

OSIR3

OR1

R2

R2

OR

R2 CO2R1R2

70-96% 74-97%ee

O

CO2Me

O

CO2Me

O

CO2Me

O

CO2Me

92% 92% ee 84% 94% ee 85% 92% ee 87% 93% ee

MeMe O



! Explotation of ion-pair intermediate in iminium catalysis


O

R2R1

NH

R

HX

N

R2R1

X

R

N

R2R1

NH HX*

X*

NH

R

HX*N

R2R1

X*

R

Amine ControlledStereoselectivity

Anion ControlledStereoselectivity

'Matched' Ion-PairControl


! Reaction works across a range of aromatic aldehydes


O

MeAr

O

OP

O

O–

i-Pr

i-Pr i-Pr

i-Pr

i-Pr i-Pr

NH2

O

(20 mol%)

NH

CO2MeMeO2C

H H

(1.1 equiv) O

MeArDioxane, 50 ˚C, 24 hr

63-90% 96-99% ee

List, B. Angew. Chem. Intl. Ed. 2006, 45, 4193-4195.


! Achieving previously unatainable results - sterically unhindered aliphatic aldehydes


O

Me

O

OP

O

O–

i-Pr

i-Pr i-Pr

i-Pr

i-Pr i-Pr

NH2

O

(20 mol%)

NH

CO2MeMeO2C

H H

(1.1 equiv)

O

Me

THF, r.t., 24 hr

71% 90% ee

Me Me Me Me

(E)-Citral (R)-Citronellal

N

NH

O Me

PhMe

Me

Me

TFA

N

NH

O Me

Me

Me

Me

TFA

58% 40% ee 82% 40% ee



! Extention to enone hydrogenation - matched-mismatched effects


O

OP

O

O–

i-Pr

i-Pr i-Pr

i-Pr

i-Pr i-Pr

(20 mol%)

NH

CO2MeMeO2C

H H

(1.1 equiv)

Bu2O, 60 ºC, 24 hr

66% 54% ee 81% 94% ee

O

Me

O

Me

R

NH3+

CO2t-Bu

i-Pr

NH3+

CO2t-Bu

CF3COO–

NH3+

CO2t-Bu

(R)-TRIP

NH3+

CO2t-Bu

(R)-TRIP

i-Pr

NH3+

CO2t-Bu

(S)-TRIP

i-Pr

66% 48% ee 45% 16% ee



! Extention to enone hydrogenation - substrate tolerance


O

OP

O

O–

i-Pr

i-Pr i-Pr

i-Pr

i-Pr i-Pr

(5 mol%)

NH

CO2EtEtO2C

H H

(1.2 equiv)

Bu2O, 60 ºC, 48 hr

68-78% 96-98% ee 99% 96% ee

i-Pr

NH3+

CO2t-Bu

89-99% 90-98% ee R = CO2Et: 99% 90% ee

O

Rn

O

Rn

O

R

O

R

O

Me

Me

Me

O

R

R = Ph: 81% 70% ee



! Extention to enal epoxidation


O

OP

O

O–

i-Pr

i-Pr i-Pr

i-Pr

i-Pr i-Pr(10 mol%)

(1.1 equiv)

Dioxane, 35 ºC, 72 hr

R = Ar: 60-84%, 98:2->99:1 dr90-96% ee

O

R

O

R

t-BuOOH

NH2

F3C

CF3

CF3

F3C

O

R = n-hex: 67%, 94:6 dr70% ee (maj), 92% ee (min)



! Tri-substituted enals have proven to be elusive substrates


O

OP

O

O–

i-Pr

i-Pr i-Pr

i-Pr

i-Pr i-Pr(10 mol%)

(1.1 equiv)

TBDME, 0 ºC, 24 hr

O

R2

O

R2

t-BuOOH

NH2

F3C

CF3

CF3

F3C

O

R1 R1

O

Me

O

Me

O

Et

O

Et

O

O

O

O

Me Me

Me

83% 94%ee 85% 94%ee 75% 90% ee85% 72:28 dr

76% ee (trans), 92% ee (cis)



! Proposed mechanism - unusual enantiodetermining step


O

Me

t-BuOOH

Me

N

MeMe

Ar Ar

TRIP

N

Me

Ar Ar

TRIPMe

O Ot-Bu

H

N

MeMe

Ar Ar

TRIP

O

t-BuOH

H2O

Ar NH2

Ar

TRIP

Ar NH2

Ar

TRIP


Weakly Coordinating Anions in Chemistry

! Non-coordinating anions – Fact or fiction?

Background to Carboranes

ClO4 BF4 PF6B(C6H5)4

> > >

decreasing coordinating ability

! Weakly coordinating anions or 'superweak anions': considerations

PF6

F– abstraction

S

O O

O CF3

Accessible

O– coordination

Prone to hydrolysis,and oxidation

B(C6H5)4

Krossing, I. Angew. Chem. Intl. Ed. 2004, 43, 2066-2090.


! What should we look for in a weakly coordinating anion?


(Or, how to make a very strong Brønsted acid)

! Low nucleophilicity

! Chemical inertness (especially to protonation!)

! Low redox activity

! Charge delocalisation

! Large size

! Peripheral atoms non-basic

! Solubility in nonpolar solvents

Krossing, I. Angew. Chem. Intl. Ed. 2004, 43, 2066-2090.


! What should we look for in a weakly coordinating anion? Candidates:


B

CF3

F3C

F3C

CF3 CF3

CF3

CF3

F3C

[B(C6F5)4]

[CB11H12]

Reviews: Strauss, S. H. Chem. Rev. 1993, 93, 927-942; Seppelt, K. Angew. Chem. Intl. Ed. 1993, 33, 1025-1027.


! A brief introduction to carborane chemistry


! Constructed of 2c-2e- and 3c2e- bonds

! Delocalised !-bonding (!-aromaticity)

! 3D-analogue of benzene

! Aromatic properties: delocalised bonding unusual stablilty propensity for substitution reactions

! Other idications: resonance energies geometries (bond order indices etc.) magnetic properties

! Very strong B-H bonds (103 kcal/mol)

Michl, J. Chem. Rev. 2006, 106, 5208-5249.


! Carborane charge distribution


Michl, J. Chem. Rev. 2006, 106, 5208-5249.


! Carborane synthesis: B-H Insertion route


B10H14 - commerciallyavailable but expensive

Michl, J. Chem. Rev. 2006, 106, 5208-5249.

NaB11H14 - 50% yield


! Carborane synthesis: B-H Insertion route


NaBH4 BF3 (OEt)+

! Carbon insertion route

NaH CHCl3

NaOEt

Michl, J. Chem. Rev. 2006, 106, 5208-5249.


! Typical reactivity of carboranes


! Electrophilic substitution

n-BuLi MeI

ICl, DME

65 ºC

I2, AcOH

25 ºC

ICl, 200ºC

Michl, J. Chem. Rev. 2006, 106, 5208-5249.


! H(CHB11Cl11) - The strongest known Brønsted acid


! "Strong yet gentle": Can protonate C60 and benzene to form isolable salts.

! Acidity only measurable by indirect (NMR) methods. Outranks HFSO3,

! HFSO3/SbF6 decomposes such molecules

! Exceptional anion stability (c.f. HSbF6 & [B(C6F5)4]–

! Stability due to weakly basic anion - large size, s-delocalisation, Cl-shielding

Reed, C. A. Angew. Chem. Intl. Ed. 2004, 43, 5352-5355 J. Am. Chem. Soc. 2006, 128, 3160-3161.

Reed, C. A. Chem. Commun. 2006, 7, 767-769 Chem. Commun. 2005, 13, 1669-1677..


! Solution to an old problem: existence of a trialkylsilylium ion (R3Si+)


! Three coordinate silicon prone to coordination by anions, solvent and even argon!

! Si-Cl bond length 2.334 Å

! Ave. C-Si-C = 116.5º


! 29Si NMR (115 ppm) therefore 'ion like'.

! Highly Lewis acidic silicon group

Reed, C. A. Chem. Commun. 2006, 7, 767-769 Chem. Commun. 2005, 13, 1669-1677..


! Solution to an old problem: i-Pr3Si!+(CB11H6Cl6)!–


! Three coordinate silicon prone to coordination by anions, solvent and even argon!

! Si-Cl bond length 2.334 Å

! Ave. C-Si-C = 117.6º


! 29Si NMR (115 ppm) therefore 'ion like'.

! Highly Lewis acidic silicon group


! Uses of a R3Si+ cation: Hydrodefluorination reactions


R F H H R H H F

catalyst

R F SiR3 H R H SiR3 F

catalyst

! Challenges:

C-F bonds are amongst the most passive functonalities in chemistry (C-F is the strongest single bond to carbon)

C-F bond strengths increase as the degree of flourination increases

C-F bonds are poor ligands and poor substrates for nuc substitution and oxidative addition

Short Review: Braun, T. Angew. Chem. Intl. Ed. 2009, 48, 2-6.

Short Review: Braun, T. Angew. Chem. Intl. Ed. 2009, 48, 2-6.




R F H H R H H F

catalyst

R F SiR3 H R H SiR3 F

catalyst

! Why do we need a hydrodefluorination reaction?

Despite the utility of fluorinated compounds (refridgerants, anesthetics, polymers, solvents, ligands, catalysts),

the high persistence of fluorocarbons is responsible for their contribution to global warming




Si-H

C-F

Si-F

C-H

favourable by~ 190 kJ / mol




Si-H

C-F

Si-F

C-H


Oserov, O. V. J. Am. Chem. Soc. 2005, 127, 2852-2853.

Max TON ~ 100

perfluorinated alkanes 0% conv




Si-H

C-F

Si-F

C-H


Oserov, O. V. J. Am. Chem. Soc. 2005, 127, 2852-2853.

Max TON ~ 100


Max TON ~ 30


alkane solvents only

Krossing, I. Tetrahedron Lett. 2007, 48, 8900-8903.

[i-Bu2-Al]+ [Al(C6F5)4]

–

[i-Bu2-Al]+ [Al{OC(CF3)3}4]

–

ori-Bu2AlH + Ph3C+M–




Ph3C[HCB11H5Cl6] Et3SiH Et3Si[HCB11H5Cl6] Ph3CH

CF3

F

F

F

F

F

CH3

F

F

F

F

F

CF3

F3C

F2C

CF2

F2C

CH2

CH3

CH3

Et3SiH

–Et3SiF

86%, 0.08 mol%TON = 1250

0%, 5% indaneremainder higher MW

28% 13%

10% <3%

>97% convTON = 200

>97% convTON = 780

Oserov, O. V. Science 2008, 321, 1188-1190.




Ph3C[HCB11H5Cl6] Et3SiH Et3Si[HCB11H5Cl6] Ph3CH

CF3

F

F

F

F

F

CF3

F3C

F2C

CF2

F2C

CH2

CH3

Et3SiH

–Et3SiF

28% 13%

10% <3%

>97% conv

TON = 200

F

F

F

F

F

53%

Cl

Cl

+ 26%

in o-C6H4Cl2 (>97% conv. TON = 1250)

76%

in benzene (>97% conv. TON = 780)

Anion Binding in Chemistry

! Area has promise for a general catalytic manifold

Conclusions

! Much work is needed towards mechanistic understanding

! Many new reactions to be discovered

! 4-years is a very short amount of time since breakthrough reactions

! Lots of scope for the design of new catalysts

anion binding in catalysis - princeton university · chiral anion mediated asymmetric chemistry!...

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