Post on 18-Aug-2020
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