chiral gold-catalyzed asymmetric reactions

Chiral gold-catalyzed asymmetric reactions

报告人：刘槟 2012年 5月 26日

Chiral gold Catalyst

Chiral gold(I)

Diphosphine ligand

monophosphine ligand

Chiral Carbene

Chiral Anion

Chiral gold(III)

Type of Chiral gold Catalyst

Ross A. Widenhoefer. Chem.Eur.J. 2008,14, 5382-5391Xiaodong Shi. ChemCatChem. 2010, 2, 609-619Veronique Michelet. Synthesis. 2011, 10, 1501-1514

From 1986 to now, more than fifty papers including three reviews:

Some leading groups : F. Dean Toste Ross A. Widenhoefer Veronique Michelet etc.

Diphosphine ligands controled Chiral gold(I) Catalysts

Fe

RCHO +CN

[Au(CyNC)2]+BF4- (1 mol%)

L* (1 mol%)

DCM , 25oCO N

R COX

O N

R COX

+

trans cis

R = Ph, 98%, 89:11R = (E)-MeCH=CMe, 89%, 91:9R = t-Bu, 100%, 100:0

96% ee95% ee97% ee

49% ee31% ee

--

NMe

H

PPh2

PPh2

NO

Au+

O

R

NO-

OMe

L*

XO

NMe

OMeX =

X = OMe,X = OMe,X = OMe,

Yoshihiko Ito, Tamio Hayashi. J. Am. Chem. Soc. 1986, 108, 6405-6406

R = Ph , 97:3R = i-Pr, 98:2R =(E)-MeCH=CHCHO, 97:3,

86% yield , 96% ee90% yield , 97% ee94% yield , 99% ee

Yoshihiko Ito. J. Org. Chem. 1995,60, 1727-1732

1.

EtOOC

EtOOC RL*(AuCl)2

H2 (4 bar), EtOH20-45 oC

EtOOC

EtOOC R

Ph

MeN

R = HR = PhR = 2-Naphthyl

20% ee80% ee95% ee

Ph

or

Ph

MeNH

Ph

or

75% ee

P

PL*=

L* AuClH2

L* AuH

AuL*

H R1 R2

Au*L

R1R2

Au OEt*L

R1 R2

R2R1

H2

EtOH

Proposed Mechanism

Avelino Corma,Chem. Commun., 2005, 3451-3453

2.

MeOOC COOMe

R

L*(AuCl)2 (5 mol %) , AgOTf (15 mol %)

MeNO2 , r.t.

MeOOC COOMe

R

MeOOC COOMe

R

+

3.572% ee

1

PAr2

PAr2Ar =L* =

R = Me , R' = H

R = Ph , R' = H

R = R' = Me

1.545% ee

1

R' R' R'

559% ee

1

Michel R. Gagne. Angew. Chem. Int. Ed. 2007, 46, 6670-6673

3.

(1)

(2)

NHTs L*(AuCl)2 (3 mol %)AgX (6 mol %)

DCE , 23oC

TsN

X = BF4X = OBzX = OPNB

82% , 1% ee27% , 98% ee76% , 98% ee

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

PAr2

PAr2Ar =L* =

NHCbz

PhPh

L*(AuCl)2 (2.5 mol %)AgClO4 (5 mol %)

m-xylene , -40oC97% , 81% ee

CbzN

PhPh

MeOMeO

PAr2

PAr2Ar =

t-Bu

t-Bu

OMeL* =

Ross A. Widenhoefer. Org Lett. 2007, 9, 2887-2889

X

NHCbz

R2

R1

L*(AuCl)2 (2.5 mol%)AgClO4 (5 mol%)

m-xylene23oC , 24h

X

CbzN R1

R2 X

CbzN R1

R2

+

(Z) (E)

X = CPh2 , R1 = Me , R2 = EtX = CPh2 , R1 = Me , R2 = n-hexylX = CPh2 , R1 = Me , R2 = t-Bu

94% (3.1:1) 96%ee / 76%ee99% (10.1:1) 91%ee / 9%ee52% (<=1:2.5) 2%ee / --

X

NHCbz

Et

Me

X

NHCbz

Et

Me

L*(AuCl)2 / AgClO4

L*(AuCl)2 / AgClO4

X

NHCbz

Et

MeAuL

L*(AuCl)2 / AgClO4

X

NHCbz

Me

EtAuL

X

N

EtMe

H AuCbzH

X

N

MeEt

H AuCbzH

X

CbzN

EtMe

H

(R,Z)

X

CbzN

MeEt

H

(R,E)

Ross A. Widenhoefer. J. Am. Chem. Soc. 2007, 129, 14148-14149

NH

COOEtCOOEt

OHNH

COOEtCOOEt

L*(AuCl)2 / AgOTf =1:2

toluene95% , 90%ee

MeOMeO

PAr2

PAr2Ar =

t-Bu

t-Bu

OMeL* =Marco Bandini. Angew. Chem. Int. Ed. 2009, 48, 9533-9537

4.

NHR

PhPh OH

L*(AuCl)2 (2.5 mol%)AgClO4 (5 mol%)

dioxane , 25oC

RN

PhPh

H

NHR

PhPh OH

[L*Au2]2+ NHR

PhPh OH

[L*Au2]2+

N OHH

PhPh

R

H[L*Au2]2+

N OH2PhPh

R

H[L*Au2]2+

RN

PhPh

H

-H2O-[L*Au2]2+

R = Fmoc , 95% ,91%ee

Ross A. Widenhoefer. Angew. Chem. Int. Ed. 2012, 51, 1405-1407

O

Ph

R


toluene OR

PhH

R = 4-MeOC6H4R = Et

56% , 96%ee24% , 91%ee

TsNPh


toluene TsNPh

H

r.t.40oC60oC

11% , 78%ee47% , 98%ee74% , 98%ee

MeOMeO

PAr2PAr2

Ar =

t-Bu

t-Bu

OMeL* =

Veronique Michelet.Chem. Commun., 2009, 6988-6990

XR

[M] = Pt, Au, Ir

XR

H

[M]

XR

H

[M]-H

XR

H

-[M] H

XR

Proposed intermediates

5.

Antonio M. Echavarren. Angew. Chem. Int. Ed. 2004, 43, 2402 –2406

PhO2S

PhO2S

R L*(AuCl)2 (1.6 mol%)AgSbF6 (2 mol%)

MeOH , r.t.

PhO2S

PhO2S

R

OMe

R = HR = Ph

89% , 53%ee52% , 94%ee

L* = PTol2PTol2

Antonio M. Echavarren. Organometallics.2005, 24, 1293-1300

ROOC

ROOC

Ph

+NMe

L*(AuCl)2 (3 mol%)AgOTf (6 mol%)

Et2O , r.t.

ROOC

ROOCN Me

H HPh

R = MeR = i-Pr

99% , 83%ee94% , 99%ee

MeOOC

MeOOC

L*(AuCl)2 (3 mol%)AgOTf (6 mol%)

Et2O , r.t.

MeOOCMeOOC

99% , 93%

MeOMeO

PAr2PAr2

Ar =

t-Bu

t-Bu

OMeL* =

Veronique Michelet. Chem. Eur. J. 2009, 15, 1319-1323

6.OPiv

+ Ar

(R)-DTBM-SEGPHOS(AuCl)2 (2.5 mol%)AgSbF6 (5 mol%)

MeNO2 , r.t.Ar

PivO76-94% ee

Ph

H OAc+ Ph

PPh3AuCl (2 mol%)AgSbF6 (2 mol%)

65%

PhPhPivO

91% ee >95:5 cis:trans, 95:5 Z:E, 0%ee

Ph

OAc L-Au

AuOAc

Ph

L

Ph

Ph

PhOAc

Ph

PhOAc

Ph

Mechanistic Hypothesis


(1)

Me OAc(R)-xylyl-BINAP(AuCl)2 (2.5 mol%)

AgSbF6 (5 mol%)

MeNO2 , -25oC

Me OAc

92% ee


(2)

(3)O

Me OPiv

Ph

MeOMeO

PAr2PAr2

Ar =

t-Bu

t-Bu

OMeL* =

L*(AuCl)2 (5 mol%)AgSbF6 (10 mol%)

MeCN, r.t.O

OPiv

Ph

74% , 97% ee

O

Me OPiv

Ph

LAu+

O

Ph

AuL

OPiv

O

Ph

OPiv

AuL

O

OPiv

Ph

O

OPiv

AuL

Ph

T.M.

Proposed Mechanisms


NO

Ph

Me

O

L*(AuCl)2 (5 mol%)AgY (5 mol%)

MeCN , 25oCN

O

O

Me

Ph

MeOMeO

PAr2PAr2

Ar =

t-Bu

t-Bu

OMeL* =

NO

Ph

Me

O

H

NO

H

O

Me

Ph

AuLFirstCyclization

1,5-H shift

NO

OMe

Ph

AuL

H

Junliang Zhang. Chem. Eur. J. 2011, 17, 3101-3104

7.

N NHt-Bu

O

+ Me5

L*(AuCl)2 (2.5 mol%)AgOTf (5 mol%)

m-xylene , 100oC

MeOMeO

PAr2PAr2

Ar =

t-Bu

t-Bu

OMeL* =

N Nt-Bu

O Me

Me5

Ross A. Widenhoefer. J. Am. Chem. Soc. 2009, 131, 5372-5373

86% , 76% ee

Markovnikov product

OHPh

L*(AuCl)2 (2.5 mol%)MX (5 mol%)

DCE , -30oC

O

Ph

MX = AgNTf2MX = NaBRAF

86% ee91% ee

Na+

B-

FF

F

FFF

F FF

FFF

FF

F

FFF

FFF

F FF

NaBARF

MeOMeO

PAr2PAr2

Ar =

t-Bu

t-Bu

OMeL* =

Proposed Mechanism

OHPh

OPh

[AuL]+

X-

H

[LAu]+ X-O

Ph[AuL]+ X-

H+

O

Ph


8.

ON

O

R2

R1

ON

O

R2

R1 Au

ON

OAu

R2

R1

R3 NR1 COOHR2

R3

ON

O

R1

R3R2

NHSO2R

(S)-Cy-SEGPHOS(AuOBz)2

(R)-xylyl-SDP(AuOBz)2

RO2SN R3


PAr2

PAr2

Ar = 3,5-xylyl

xylyl-SDP

9.

R

L*(AuCl)2 (5 mol%)AgSbF6 (20 mol%)

1:9 DCM:DCE , -35oCR

R = Ph

R =

89% , 87%ee

94% , 93%ee

PAr2

PAr2

Ar = 3,5-xylylL*=

Dean J. Tantillo , Michel R. Gagne. Nature Chemistry. 2012, 4, 405-409

10.

Monophosphine ligands controled Chiral gold(I) Catalysts

TsN

[Au] AgSbF6

TsN

H

H

DCM

(R)-DTBM-SEGPHOS(AuCl)2 r.t.(S,S,S)-L1AuCl -15oC(R,R,R)-L2AuCl -15oC

+TsN

H

H

-- (1:1.7) 8%ee82% (14:1) 80%ee82% (16:1) 90%ee

OO P N

Ph

PhL1 = O

O P NPh

PhL2=

TsNR

R

[Au]TsN

R

R+[Au]

TsN[Au]

RRH

H

[4+3]

[4+2]

[2+2]

Jose L. Mascarenas. J. Am. Chem. Soc. 2009, 131, 13020-13030

1.

MeOOCMeOOC

R

R

OO

L1*AuCl (5 mol%)AgBF4 (5 mol%)

up to 92% eeMeOOCMeOOC

RRH

H

TsN

R

RL2*AuCl (5 mol%)AgBF4 (5 mol%)

up to 92% ee TsN

RR

H

H

O

3P

L1*

OO

PNPh

Ph

R'

R'

R' =

L2*

F. Dean Toste. Org Lett, 2010, 12, 200-203

MeOOC COOMe

Ph

L*AuCl (5.5 mol%)AgBF4 (5 mol%)

DCM , 0oC

MeOOC COOMe

H H

PhO

O

O

OP

Ar Ar

Ar Ar

N

Ph

Ph

L* =

91% , >99%ee Ar = 4-(tert-Butyl)phenyl

Veronique Michelet . Angew. Chem. Int. Ed. 2010, 49, 1949 ¨C1953

2.

Similar work by F. Dean Toste using Phosphoramidite Gold(I)

F. Dean Toste . J. Am. Chem. Soc. 2011, 133, 5500–5507

R1

N

H

R2

+ R3 + p-TsNCOL*AuCl (5 mol%)AgNTf2 (5 mol%)

CHCl3 , r.t.

N OR2

R1 R3

NTs

+ N OR2

NTs

R3R1

majormoderate to high regio andenantioselectivities

PPh3

NH

NHOS OO

i-Pri-Pr

i-Pr

L* =

Ph

ArHN O

NHTs

PhLAu

ArHN O

NH Ts

AuLPhPh

ThermodynamicArHN O

NTsH

Ph PhLAu

Kinetic

-AuL+

ArHN O

NTs

PhPh

-AuL+

ArHN O

NTs

Ph Ph

-Favored with small ligands-Increasing rate of protodeauration should futher favor trapping of the kinetic product

Appreciable formation with large ligands

F. Dean Toste .Chem. Sci., 2011, 2, 1369-1378

3.

Chiral Carbene controled gold(I) Catalysts

TsN

Ph

NHC-Au(I) cat.1 (5 mol%)AgSbF6 (5 mol%)

AcOH (20 eq. dry) , DCE0oC

TsN

OAc

HH Ph

>99% , -59% ee

X

Ar

NHC-Au(I) cat.2 (5 mol%)AgSbF6 (5 mol%)

Ph2SO (1.5 eq.) , PhCl4A MS , 10oC

X

86-99% yield, 3-70% ee

CHO

H

Ar N

NHAc

N

AuI

N

N

N

AuIcat.1

cat.2

TsN

Ph

AuL*

TsN

Ph

*LAu

TsN

*LAu

H

Ph

TsN

*LAu

H

Ph

TsN

Ph

HAuL*

H

TsN

Ph

O=SR2TsN

H

Ph

*LAuO

SR2-SR2

TsN

H

Ph

O

TsN

*LAu

H

Ph

NuH

OAcTsN

OAc

*LAu

HPhH

H+

TsN

OAcH

PhH

intramolecular rearrangements of 1,6-enyneShi Min .Organometallics .2011, 30, 3859-3869

NCR

Au(THT)Cl NCR

AuClHNR'2

NR

NR'

R'H

AuCl

R' = i-Pr , R = H (a) R = Ph (b) R = 3,5-(CF3)2C6H3 (c)R' = (S)-MePhCH , R = 3,5-(CF3)2C6H3 (d)

O

Ph

+ i-PrOH(2 eq.)

catalyst (5 mol%)LiNTf2 (4.5 mol%)

DCE

O

Ph

Oi-Pr

cat. = (a)cat. = (b)cat. = (c)cat. = (d)

12% , 8%ee28% , 61%ee68% , 84%ee70% , >99%ee

LeGrande M. Slaughter. Angew. Chem. Int. Ed. 2012, 51, 2912-2915

Chiral Anions controled gold(I) Catalysts

OH

L* = Chiral Diphosphine ligands

L*(AuCl)2 / AgX = 1:1

DCM

OH

52~89% , <10%ee

OH L(AuCl)2 or LAuCl , AgX

Solvent

OH

OO

POO-X =

L = PPh3 (5 mol%) , X (5 mol%) , in DCM

L = dppm (2.5 mol%) , X (5 mol%) , in benzene

R

RR = 2,4,6-i-Pr3-C6H2

89% , 48% ee

90% , 97% ee

A

B

CO

OH(S)-BINAP(AuCl)2 (2.5 mol%)

(R)-AgX(5 mol%)

benzene , 23oC

OH

O

88% , 82% ee

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

Other Chiral Au(I)/Au(III) Catalysts

NO

N N

O

OHHAu

ClCl

Avelino Corma. Journal of Catalysis, 2009, 265,238-244

N N

Ph Ph

R1R1

R2

R2 R2

R1R1

R2

AuCl

Kiyoshi Tomioka. Tetrahedron Letters. 2010,51,404-406

H

H

AuCl

Constantin Czekelius. Chem. Eur. J. 2009, 15, 13323-13326

PN

ClAu

R'

R'

R

R

P

R

R

P

R

R

NR'

ClAu

ClAu

P

R

R

PR

R

P

R

R

N

AuCl

ClAu

AuCl

Lutz H. Gade. Chem. Eur. J. 2012, 18, 3721-3728

Conclusion

•手性 Au(I)催化的不对称反应最早可追溯到 86年 Ito与 Hayashi的 Adol反应，使用手性二茂铁膦配体。由于 Au(I)配合物为线性配位模型，手性配体与催化剂活性位点距离较远，很难创造合适的手性环境。之后直至2005年手性金催化的反应才开始逐渐发展起来，目前主要的例子多集中于手性双膦配体的双金属催化剂。另外以手性 Phosphoramidite 为代表的单膦配体，手性卡宾配体以及由 Toste提出的手性磷酸阴离子控制的手性Au(I)催化剂也有少数例子。•目前，手性金催化剂的发展还存在很多问题没有解决。例如，同其他金属相比金催化的反应多存在底物较窄的问题。手性双膦配体的双金属催化剂中第二个金属中心所起的作用并不明确。而手性单膦配体及手性卡宾金催化的例子较少且有一部分例子只能得到中等 ee值。其他类型的手性配体也有待开发，如大位阻的手性硫脲类配体等等。

N N

S

t-Bu

t-But-Bu

t-Bu

AuCl

Dan Yang. Synthesis, 2007,16, 2539-2544

chiral gold-catalyzed asymmetric reactions

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