Vincent GandonVincent Gandon

Institut de Chimie Moléculaire et des Matériaux d’Orsay, UMR 8182 Institut de Chimie Moléculaire et des Matériaux d’Orsay, UMR 8182 Université Paris-sudUniversité Paris-sud

Mécanismes réctionnels en catalyse homogène :

Assistance de la chimie théorique

Les simulations numériques en chimie à Paris-sud

24 octobre 2012

Asymmetric Carbocyclizations: Chiral Anion Strategy

p-TsN

Me

IrCl(CO)(PPh3)2 (10 mol%)

Toluene, 90 °C23 h, c 0.134M

Ph

silver phosphate (12 mol%) p-TsNPh

Me

83%, 47% ee

O

OP

O

OAg

tBu

tBu

74%, (85% ee)

O

OP

O

OAg

32%, 37% ee

O

OP

O

OAg

CF3

CF3

CF3

CF3

O

OP

O

OAg

iPriPr

iPriPr

iPr

iPr

80%, 81% ee

Asymmetric Carbocyclizations: Chiral Anion Strategy

OO

P

O

O

IrPPh3

Ph3P

OC

Asymmetric Carbocyclizations: Chiral Anion Strategy

TsN PhMe

Toluene, 92 °C,

ClIr

COPh3P

PPh3

(0.02 mmol)

(S)-P* (0.024 mmol)

(0.1 mmol)

(CO 1962 cm-1)

(CO 1966 cm-1)

reaction mixture

sealed tube

(CO 1966 cm-1)

O

OP

O

O

IrPPh3

Ph3P CO

25.6 ppm

14.8 ppm

25.5 ppm

3.4 ppm

25.5 ppm

3.4 ppm

31P NMR

Toluene, rt, 15 h

NTs

Ir

CO

H3P PH3

0.0

6-endo11.54

-17.22

NTs

IrOC

PH3

H3P

-6.12

-37.87NTs

Ir

CO

PH3H3P

1,2-H shif tPh

Ph

Me

Me

MePh

Asymmetric Carbocyclizations: Chiral Anion Strategy

DFT, DFT, GG298298 (kcal/mol) (kcal/mol)B3LYP/LANL2DZ/6-31G**

Asymmetric Carbocyclizations: Chiral Anion Strategy

NTsPhMe

+ [Ir(CO)(PH3)2]+OO

POO

NTs

Ph

MeNTs

Ph

Me

Chem. Eur. J. 2011, 17, 13789

Cyclization of Diynyl Esters

O

Ph

O

O Ph

OSiO2

PhO

O Ph3PAuClAgSbF6

OCOR

•

OR'

R'

OR

O

R'

R

O

Au+

Au+5-exo

Au

O

R'

R O

AuH

O

O

Au

H3P

•

Au

PH3

O

Au

PH3

O

O

H

OH3P

(0.0)

+1.0

(-28.2) (-29.5) (-57.8)

+5.4O

O

+7.8

ACIE 2011, 6868

DFT, DFT, HH298298 (kcal/mol) (kcal/mol)B3LYP/LANL2DZ/6-31G**

Cyclization of Diynyl Esters

Au+

+

Ph

O

CD3

O

+

O O

t-Bu

O O

O

Ph

O

D3C

O

t-Bu

O O

O

H3C

Cyclization of Diynyl Esters

92%

AuClPPh3 (2 mol%)AgSbF6 (2 mol%)

CH2Cl2, rt, 10 min

AcO

H

AcO

H

OR2

OR2

HHR1 = H, R2 = Ac, 98%R1 = Me, R2 = PNB, 96%

92%

R1

R1

R1

R1

OAc

OAc

OL 2007, 2207

1-Allene Gold Complexes

Linear Triquinanes: Synthesis of 9(12)-Capnellene

JACS 2009, 2993

TBSO OAc

TBSOH H

OAc

CH2Cl2, 0 °C2 h 85% (2 steps)

TBSOH H

OH

K2CO3(20 mol%)

MeOH

Au PtBu

tBu

SbF6

(2 mol%)

MeCN

-+

LiAlH4,THF, 0 °C

H H

H

BuLiPh3PMeBr

capnellene, 77%

TBSOH H

H

OH H

H81% (2 steps)

1- PtO2, H22- NaH, CS2, MeI3- Bu3SnH, AIBN

59% (3 steps)

1- TBAF2- Dess-Martin

TBSOH H

OHH

85%

•AcO

H

Au+

AcOH

Au

AcOO

HO

+Au

O O O

Au

O

Au+

Au+

1-Allene Gold Complexes

Au

+H

Me

H

MeAu

H

Me

H

Me

AuBr3

0.0 1.4

+

DFT, DFT, HH298298 (kcal/mol) (kcal/mol)B3LYP/LANL2DZ/6-31G**

1-Allene Gold Complexes

Au

+H

Me

Me

MeAu

H

Me

Me

Me

AuBr3

10.0 0.0

+

DFT, DFT, HH298298 (kcal/mol) (kcal/mol)B3LYP/LANL2DZ/6-31G**

1-Allene Gold Complexes

Chirality Transfers

ACIE 2008, 7534

AuCl(PPh3) (2 mol%)AgSbF6 (2 mol%)

CH2Cl2, 20 °C, 2 hOAc

OAc

92% ee 90% ee

• 1-5 mol% [(Ph3PAu)3O]BF4

CHCl3, 60 °C

exo-Cyclizations

•

AuL+

AuL+

•

LAu

•

AuL

LAuLAu

HAuL

H

H+

+ H+

AuLH

AuL+

- AuL+

LAu

LAu+

ACIE 2006, 7596

Toste, Houk JACS 2008, 4517• 1-5 mol% [(Ph3PAu)3O]BF4

CHCl3, 60 °C

exo-Cyclizations

•

AuL+

AuL+

•

LAu

•

AuL

LAuLAu

HAuL

H

H+

+ H+

AuLH

AuL+

- AuL+

LAu

LAu+

Polynuclear Gold Complexes

+Cat. (2 mol%)

CHCl3

Cat. Conditions % Yield (rat io)

ABC

RT, 1 hreflux, 7 hRT, 1 h

87 (20 : 1)35 (1 : 0)100 (5 : 1)

A: Ph3PAuNTf2 B: (Ph3PAu)3OBF4 C:P AuSbF6

t-But-Bu

MeO

MeO

MeO

MeO

MeO

MeO

1

[1 H + (Ph3PAu)2]+

m/ z 1099

[1 H + ((biph)(t-Bu)2PAu))2]+

m/z 1171

OMeOMe

B

C

(+)

ES

Iin

fus

ion

inC

DC

l 3

A

A: Ph3PAuNTf2B: (Ph3PAu)3OBF4

C:

P Au+ , SbF6-

t-But-Bu

Mass spectroscopy (CAR)Mass spectroscopy (CAR)

Polynuclear Gold Complexes

MeO

MeO

AuPR3

AuPR3

AuPPh31 equiv

Traces70

5 mol%

Ph3PAuNTf2 (mol%)

510

% Yield

RT

MeO MeO

MeOMeO

MeO

MeOPh3PAuNTf2

Intermediacy of Gold Acetylides?

Intermediacy of Gold Acetylides?

AuPPh3+

MeO

MeO

AuPPh3

AuPPh3

AuPPh31 equiv

Traces70

5 mol%

Ph3PAuNTf2 (mol%)

510

% Yield

RT

MeO MeO

MeOMeO

MeO

MeOPh3PAuNTf2

Intermediacy of Gold Acetylides?

Chem. Sci. 2011, 2, 2417

AuPH3 H3PAu

G = 0.0 G = 26.9 G = 20.2 G = 10.3

+ H3PAuOH + H3PAuOH2++ (H3PAu)2OH+ + H2O

H3PAu

AuPH3

AuPH3 H3PAu

G = 0.0 G = 33.0 G = 24.4 G = 35.1

+ H3PAu+

+ H2O+ H3PAu+

+ H3O+

+ 2 H3PAu+

+ H2O+ H3O+

H3PAu

AuPH3

DFT, DFT, GG298298 (kcal/mol) (kcal/mol)B3LYP/LANL2DZ/6-31G**

Facilities

Paris 6 CRIHAN

ICSN

IDA