PLATINUM AND

GOLD

CATALYZED

REACTIONS

Reviews:

A. Fürstner, P. W. Davies, Angew.

Chem. Int. Ed. 2007, 46, 3410

A. Fürstner, Chem. Soc. Rev.

2009, 38, 3208

A FORMAL “ENYNE METATHESIS”

MeOOC

MeOOC

MeOOC COOMe

97%

PtCl2 cat.

S. Murai et al., J. Am. Chem. Soc. 1994, 116, 6049; Organometallics 1996, 15, 901

„The reaction mechanism is not clear at present and must await further study“

THE PRODIGIOSIN ALKALOIDS

for a review on the chemistry and biology of the prodigiosins see:

A. Fürstner, Angew. Chem. Int. Ed. 2003, 42, 3582

immunosuppressive – synergistic action with cyclosporin and FK506 in vivo

NN

H

MeO

NH

Streptorubin B

N

NN

H

MeO

ON

R

H

R

NHH

A. F. with H. Szillat, B. Gabor, R. Mynott, J. Am. Chem. Soc. 1998, 120, 8305

OUR “INITIATION”

Mechanistic proposal:

A GENERIC THREE-STEP MECHANISM

for a detailed discussion, see:

Chem. Soc. Rev. 2009, 38, 3208

789 ppm

213 K

243 K

273 K

Z Z

E

3a

Ph3P

C25

C24

C26

C23

C21

C22

C35

C34

C36

C33

C31

C32

P1

C12

C11

C13

Au1

C14

C16

C8

C4

C15

N3

C5

C2

N6

C1

C7

Chem. Eur. J. 2009, 15, 8558

Angew. Chem. 2008, 120, 3254

Angew. Chem. 2009, 121, 2548

O2

N1

O3O1

P1

O4

Au1

Cl

asymmetric catalysis: Angew. Chem. 2010, 122, 1949

A. F. with S. Flügge, A. Anoop, R. Goddard, W. Thiel, Chem. Eur. J. 2009, 15, 8558

C38C12

C26

C1

C39

C2

C3

C37

C11

C6

C25C5

C27

C9

C32

C4

Au1

C20

C33C10

C21

C31

C8

C19

C7

C13

C28

C16

N2

N1

C30

C18

C29

C17

C15

C14

C23C22

C34C35

F2

F6

C36

C24

Sb1F1

F4

F3

F5

C11C12

C9

C8C1

C10

Au1

Cl1

C2

C5

C7

C6

C3C4

C25

C24

C26

C23

C21

C22

C35

C34

C36

C33

C31

C32

P1

C12

C11

C13

Au1

C14

C16

C8

C4

C15

N3

C5

C2

N6

C1

C7

A. Fürstner, M. Alcarazo, R. Goddard, C. W. Lehmann, Angew. Chem. Int. Ed. 2008, 47, 3210

SLIPPAGE

789 ppm

213 K

243 K

273 K

Z Z

E

3a

Ph3P

A. F. with G. Seidel, R. Mynott, Angew. Chem. Int. Ed. 2009, 48, 2510

For the development of Ph3PAuNTf2:

F. Gagosz et al., Org. Lett. 2005, 7, 4133

A. F. with G. Seidel, R. Mynott, Angew. Chem. Int. Ed. 2009, 48, 2510

for a general discussion of the „carbene/cation“ conundrum, see: A. Fürstner, Chem. Soc. Rev. 2009, 38, 3201

CATIONS OR CARBENES ?

the “Stork-Eschenmoser paradigm“ of cationic polyene cyclizations

applies to gold catalyzed cyclization cascades

A. Fürstner, L. Morency, Angew. Chem. Int. Ed. 2008, 47, 5030

gem-DIAURATION versus PROTODEMETALLATION

C14

C13

C54

C33

C55

C34

C32

C15

C12C53

C56

C11

C16

C35

C3

C31

C4

C52

F6AC36

C51

P1

C2

O1

O3A

Au1

F4A

C68A

C46

N1A

Au2

F5A

C26

C21

P2

C1

C45O5A

S1

S2A

O2A

C41

F2A

C61

C25

C22

C62

C67

C5

C66A

C44

F3A

O4AC42

C24

C23

C63

C65A

C43

F1A

C64A

gem-DIAURATION

A. F. with G. Seidel, C. W. Lehmann, Angew. Chem. Int. Ed. 2010, 49, 8466

C44

C43

C34

C45

C35

C42

C33

C46

C36

C41

C32

F3

C31

C13

C14

F1

C12

C52

C65

O2

C66

C64

C61

P2

C71

C53

C15

C62

C11

C63

C51

C16

P1

S1

F2Au2

N

Au1

C54

O1

C2

C56

C21

C4

C1

C55

C26

C5

F4A

C22

C3

S2 O4A

F5A

C72

C25

C23

O3A

C24

F6A

A. F. with G. Seidel, C. W. Lehmann, Angew. Chem. Int. Ed. 2010, 49, 8466

gem-DIAURATION

O4

O2

Cl1

Au1

P1

N1O3

O1

ASYMMETRIC GOLD CATALYSIS –

TADDOL LIGANDS WITH AN ACYCLIC BACKBONE

A. F. with H. Teller, S. Flügge, R. Goddard, Angew. Chem. Int. Ed. 2010, 49, 1949

STEERING THE COURSE OF GOLD CATALYZED REACTIONS

BY UPREGULATION OF THE ACCEPTOR PROPERTIES OF NHC„S

A. F. with M. Alcarazo, T,. Stork, A,. Anoop, W. Thiel, Angew. Chem. Int. Ed. 2010, 49, 2542;

HYPOTHESIS DRIVEN

DISCOVERY

“...[the reactive intermediate] .... is carbenoid in nature.”

A. Fürstner, H. Szillat, F. Stelzer, J. Am. Chem. Soc. 2000, 122, 6785

HYPOTHESIS DRIVEN DISCOVERY

PtCl2 cat.

toluene+

N

Ts

D

H

N

Ts

D

D

N

Ts

D

D

N

Ph

Ts

N

Ts

N

Ts

SiMe3

N

Ts

Bu

O

PhPh

78% 69% 73% 87% 83%

HYPOTHESIS DRIVEN DISCOVERY

A. Fürstner, P. W. Davies, T. Gress, J. Am. Chem. Soc. 2005, 127, 8244

E E

OiPr

HH

H

H

H

EE

O

84% 84%91%

H

H

H

EE

Ph

PtCl2 cat.

CO (1 atm)

Ar

E E

H

H

H

Ph

EE

76%

X-ray

OH

Ph

PtCl2 cat.

toluene, 80°C Ph

O

ee = 92% ee = 92%

REARRANGEMENT OF HYDROXYLATED ENYNES

O O

O

O

Ph

O

Ph

O

Ph

O

Ph

O

81% 60% 66% 52% 75% 68%

SYNTHESIS OF SABINOL

V. Mamane, T. Greß, H. Krause, A. Fürstner J. Am. Chem. Soc. 2004, 126, 8654

HO

O

PtCl2 (5 mol%)

toluene, 80°C, 2h

NaBH4, CeCl3

OH

trans-sabinol

65%

sabinone

78%

O

SiMe3

BF3

see also: M. Malacria et al., JACS 2004, 126, 8656; F. D. Toste et al., JACS 2004, 126, 10858

CONCOMITANT ACETATE WALK

V. Mamane, T. Greß, H. Krause, A. Fürstner J. Am. Chem. Soc. 2004, 126, 8654

see also: F. D. Toste et al., JACS 2005, 127, 5802

O

Ph

O

[Au]

Ph

AcO

Ph

O

AcO

Ph

K2CO3

MeOH

(Ph3P)AuCl (2%)

AgSbF6 (2%)

CH2Cl2, r.t.

74% overall

APPLICATION TO TOTAL SYNTHESIS

A. Fürstner, P. Hannen, Chem. Eur. J. 2006, 12, 3006

see also: A. Fürstner et al., Chem. Commun. 2004, 2546 (sesquicarene).

Review on Iron Catalyzed Cross Coupling:

A. Fürstner et al., Chem. Lett. 2005, 34, 624

HAcOH

HTfOH

HMeH

O

O

PtCl2 cat.

MeMgBr

Fe(acac)3 cat.

90%

-cubebene

O

toluene, 80°C

92%

A. Fürstner, A. Schlecker, Chem. Eur. J. 2008, 14, 9181

analogously:

CARBOALKOXYLATION

M

E

XM

X

E

M

Y

OO

M

Y OYO

Y

M

Y = COOR, CN

O

COOMe

PtCl2 (5 mol%)

toluene, 80°C

73%

OMeOOC

A NOVEL Pt(II)-CATALYZED CARBOALKOXYLATION

A. Fürstner, F. Stelzer, H. Szillat, J. Am. Chem. Soc. 2001, 123, 11863

OE

Ph

O

EO

CN

O

CN

O

CN

76% 56%86% 77% 80%

O Ph

R

O

OMe

N Ph

Ms

94% (R = H)

71% (R = Me)

98%

59%

HETEROARENES

A. Fürstner, P. W. Davies, J. Am. Chem. Soc. 2005, 127, 15024

MIGRATION OF OTHER “STABILIZED CATIONS”

O

OMe

Ph O

OBn

Ph O

O

Ph

SiMe3

84% 78% 81%

O

OMe

O

OMe

CF3

O

O SiMe3

Br84% 75% 74%

A. Fürstner, P. W. Davies, J. Am. Chem. Soc. 2005, 127, 15024

APPLICATION

A. F. with E. Heilmann, P. W. Davies, Angew. Chem. Int. Ed. 2007, 46, 4760

ELECTROPHILIC CYCLIZATIONS

CARBO- AND HETEROCYCLES BY C-C-BOND FORMATION

RX

M

M

R

X

R

X

X

R

6-endo

5-exo

A. Fürstner et al, J. Org. Chem. 2002, 67, 6264; Chem. Eur. J. 2004, 10, 4556

larger scale application: Org. Synth. 2006, 83, 103

catalyst (5 mol%) N Ncatalyst (5 mol%)

PtCl2 (76%)

AuCl3 (95%)

GaCl3 (53%)

InCl3 (44%)

PtCl2 (< 40%)

AuCl3 (< 40%)

GaCl3 (80%)

InCl3 (91%)

NPh

N

Me

Me

NH

S

Ph

76% 93%94% 88%

MeO

MeO

Me

Me

Me

O

O MeO

Cl

MeO

OMe

OMe

95% 56% 94% 81%

OMe

MeO

MeO

Br

X

X = H

X = I

OMe

MeO

MeO

Br

N

O

O

OMe

MeO

MeO

NR2

Br

R, R = phthalimido

R = H

OMe

MeO

MeONH

OMe

MeO

MeO

NR2

O

OMe

MeO

MeO

NR2

Br

N

O

O

1. Pd(0),

2. Crabtree's catalyst, H2

B(OH)2

O

57%

Pd(O)

94%

I2, Hg2O

81%

1. CBr4, PPh3, 88%

2. DBU, 79%

InCl3

87%

H2NNH2quant.

CuI, CsOAc

71%

from Gutteria ouregon

OMe

MeO

MeONH

HN

OMe

OMe

OMe

CuCl2.2 H2O

tBuNH2, MeOH

86%

isolated from Polyalthia bullata

A. Fürstner, V. Mamane,

Chem. Commun. 2003, 2112

HIGHLY CYTOTOXIC PHENANTHROQUINOLIZIDINE-

AND PHENATHROINDOLIZIDINE ALKALOIDS

OMe

MeO

B(OH)2

I

Br

MeO

NBoc N

Boc

MeO

OMe

MeO

PtCl2 cat.

MeO

OMe

MeO

NBoc

97%

MeO

OMe

MeO

N

Cryptopleurine

A. Fürstner, J. Kennedy,

Chem. Eur. J. 2006, 12, 7398AntofineMeO

OMe

MeO

N

H

TylophorineMeO

OMe

MeO

N

H

OMe

FicuseptineMeO

N

H

O

O

ACTIVATION OF ALKENES:

THE METHYLENECYCLOPROPANE CASE

R

PtCl2

RPtCl2

PtCl2

R

HPtCl2

R

HR

H PtCl2

PtCl2

R

R

Ph

PtCl2 (1 mol%)

CO (1 atm)

toluene, 40°C Ph

D

D

77%

> 98% D-incorporation

BnO

MeOOC MeO

MeO

Br

TBSO

Ph90% 80% 61%

93%

95%

A. Fürstner, C. Aissa, J. Am. Chem. Soc. 2006, 128, 6306

A. Masarawa, A. Fürstner, I. Marek, Chem. Commun. 2009, 5760

CYCLOBUTENES WITH CHIRALITY TRANSFER

and/or

B A'

A

SiCl

OSi

R

XMCl

SiClXM

SiClXM

+

+

-

-

MX

"halophilic

promoter"

R

OSi

Cl

RCHO

1

PLATINUM(II)-CATALYZED

SAKURAI ALLYLATIONS

A. Fürstner, D. Voigtländer,

Synthesis 2000, 959

PLATINUM(II)-CATALYZED SAKURAI ALLYLATIONS:

DIASTEREO-DIVERGENCE

A. Fürstner, D. Voigtländer, Synthesis 2000, 959

Z:E = 6:94 anti

RCHOSiMe2Cl R

OH

PtCl2 cat.

Z:E = 99:1 syn

SiMe2Cl RCHO

PtCl2 cat.R

OH

OH

Ph

OH

Ph

OH

90% (6:94) 93% (9:91) 91% (6:94)

OH

Ph

OH

Ph

OH

92% (99:1) 92% (98:2) 91% (97:3)

PLATINUM CATALYZED FRIEDEL-CRAFTS ACYLATION

ortho : para > 1 : 99

MeO

hexanoic acid anhydride

77%

AgSbF6 (5 mol%)

(PhCN)2PtCl2 (2.5 mol%)

MeO

O

O O

O

O

OOMe

O

O

S

Ph

O

76% 70% 61% 61% 92%

A. Fürstner, D. Voigtländer, W. Schrader, D. Giebel, M. T. Reetz, Org. Lett. 2001, 3, 417