Transcript lj - University of Ottawa

Gold-Catalyzed Reactions:
A Treasure Trove of Reactivity
By: Nathalie Goulet
March 9, 2006
Overview
- Introduction
- Reactivity of gold with alkynes
- Activation of allenes
- C-H bond activation
- Enantioselectivity
- Synthesis
- Carene terpenoids
- Jungianol
- Conclusions
2
Gold
- Preconceived notion that gold is expensive
Complex
Price for 1 g
$/mol
Complex
Price for 1 g
$/mol
AuCl
197$
45 786
AuCl3
170$
51 566
PtCl2
260$
69 160
RhCl3
260$
54 368
PdCl2
95$
11 144
RuCl3
97$
20 108
- Gold used to be thought of as chemically inert
- Oxidation states of gold
• -1 : auride compounds; e.g. CsAu, RbAu
• 1 : aurous compounds; e.g. AuCl
• 3 : auric compounds; e.g. AuCl3
• 5 : e.g. AuF5
3
Prices from Aldrich catalogue
Gold
79
Au
196.97
4
http://www.molres.org/cgi-bin/pt-request
Properties of Au: A Late Transition Metal
Pauling electronegativities of the transition elements
Sc
1.3
Ti
1.5
V
1.6
Cr
1.6
Mn
1.6
Fe
1.8
Co
1.9
Ni
1.9
Cu
1.9
Y
1.2
Zr
1.3
Nb
1.6
Mo
2.1
Tc
1.9
Ru
2.2
Rh
2.3
Pd
2.2
Ag
1.9
La
1.1
Hf
1.3
Ta
1.5
W
2.3
Re
1.9
Os
2.2
Ir
2.2
Pt
2.3
Au
2.5
- More electronegative metals tend to retain their valence electrons
- Low oxidation states for late transition metals are more stable than
higher ones
- Back donation in late transition metals is not so marked compared
to early transition metals
- Gold is a soft transition metal and thus will prefer soft transition
partners
Crabtree, R. H., The 0rganometallic Chemistry of the Transition Metals, John Wiley & Sons, Inc, New York, 2001, p.46
5
Crystal Field Theory
- d orbitals of a metal are affected by the presence of ligands where
the ligands act as a negative charge
Mn+
ML6n+
dx2-y2
dz2

dyz
dxz
dxy
Octahedral geometry
Crabtree, R. H., The 0rganometallic Chemistry of the Transition Metals, John Wiley & Sons, Inc, New York, 2001, p.46
http://science.kennesaw.edu/~mhermes/cisplat/cisplat06.htm
6
Why Are d8 Metals Square Planar?
dx2-y2
dx2-y2 dz2

dxy dyz dxz

dxy

dz2
dxy dyz dxz
dxz dxz
Square Planar
Octahedral
dx2-y2 dz2
Tetrahedral
- The square planar geometry offers the electrons never to be placed
in the highest energy orbital
- d10 metals fill all the d orbitals
- Conformation that offers less steric hinderance for the ligands
Au(III): X
L
L Au X
Au
X
Au(I):
X
Crabtree, R. H., The 0rganometallic Chemistry of the Transition Metals, John Wiley & Sons, Inc, New York, 2001, p.46
7
Lewis Acid Activation
Hard Lewis acids:
- small
- high charge states
- weakly polarizable
- often activate reactions by coordination to the oxygen atom.
- e.g. Ti4+ and Fe3+
Soft Lewis acids:
- big
- low charge states
- strongly polarizable
- often activate the reaction through coordination with the π bond
- Cu+ and Pd2+
Au(III) is more oxophilic than Au(I) and so is a harder
Lewis acid
Au(I) will have a higher affinity for alkynes
8
Reactivity of Alkynes
- The LUMO of alkynes are low in energy and so will eagerly react with
strong nucleophiles
- Unless activated, alkynes will not react with weak nucleophiles
- Using its d orbitals, gold can activate alkynes by interacting with both
π orbitals of the alkyne
σ-type donation:
Π-type donation:
dxz
dx2-y2
Π-type
back-donation:
δ-type
back-donation:
dxy
Toreki, R. http://www.ilpi.com/organomet/alkyne.html, 20/11/2003
Hashmi, A. S. K. Gold Bulletin, 2003, 36, 3-9
dyz
9
Reactivity of Alkynes
- Terminal alkynes can interact through a second mode of action
especially with AuI
LAuX
R
H
R
AuL
base
- Forms a gold(I)-alkynyl complex
- stable
- will not readily react with nucleophiles
η1-Au-η1:
tBu
η2-Au-η1:
tBu
Au
tBu
Au
Hashmi, A. S. K., Gold Bulletin, 2003, 36, 3
tBu
Mingos, D. M. P.; Yau, J.; Menzer, S.; Williams, D. J. Angew Chem. Int. Ed. 1995, 34, 1894
10
Reactivity of Alkynes
Nu
[Au]
Nu
Nu
[Au]
[Au]
- A broad range of nucleophiles may be used
-Carbon-carbon bond forming reactions:
- Propargyl-Claisen rearrangement
- Carbon-oxygen bond forming reactions:
- Ketone or acetal formation
- Carbon-nitrogen bond forming reactions:
- Acetylenic Schmidt Reaction
11
Propargyl Claisen Rearrangement
- Claisen rearrangement:
O
O
- Can be catalyzed by:
- Hard Lewis acids by coordination to the oxygen atom
- Soft Lewis acids by coordination to the π bond
- e.g. Hg(II) and Pd(II)
- Propargyl Claisen rearrangement
- Typical soft Lewis acids cannot be used
LA
O
O
Sherry, B. D.; Toste, F. D. J. Am. Chem. Soc. 2004, 126, 15978-15979
X
O
12
Propargyl Claisen Rearrangement
- Gold is so alkynophilic that it will prefer binding to the alkyne than to the
vinyl ether
O
[(Ph3PAu)3O] BF4 (1.0 mol%)
CH2Cl2, rt
R1
R2
R2
OH
R1
NaBH4, MeOH, rt
R3
R3
O
Entry
R1
R2
R3
Yield
1
p-MeO-C6H4
H
n-C4H9
89%
2
p-CF3-C6H4
H
Me
86%
3
PhCH2CH2
Me
Me
91%
Hard LA or
Ph

[(Ph3PAu)3O] BF4 (1.0 mol%)
CH2Cl2, 15 min, rt
O
OH
Ph
Sherry, B. D.; Toste, F. D. J. Am. Chem. Soc. 2004, 126, 15978-15979
NaBH4, MeOH, rt
80%
Ph
13
Interaction of Gold with Alkynes
O
[(Ph3PAu)3O] BF4 (1.0 mol%)
CH2Cl2, rt
R1
R2
R
OH
H
R3
OH
R1
NaBH4, MeOH, rt
R
NaBH4
R2
R3
R1
O
O
H
R
R1
R1
H
R
[Au]
Sherry, B. D.; Toste, F. D. J. Am. Chem. Soc. 2004, 126, 15978-15979
H
Au
O
O
H
R1
H
R1
R
Au
14
Active Catalyst: AuI or AuIII
- Many reactions can use either AuI or AuIII. Sometimes one is faster
than the other, however the active catalyst remains unknown
- Reduction of high oxidation state pre-catalyst to catalyst is
mandatory in several late transition state metal catalyzed
reactions
- AuCl3-catalyzed benzannulation by Yamamoto was studied using
B3LYP, a DFT calculation method
O
Me
H
AuCl3
+
R
Me
Straub, B. F. Chem. Commun. 2004, 1726-1728
Asao, N.; Tokahashi, K.; Lee, L.; Kasahara, T.; Yamamoto, Y. J. Am. Chem. Soc. 2002, 124, 12650-12651
O
R
15
Active Catalyst: AuI or AuIII
Yamamoto’s Proposal:
CHO
R2
R1
O
R
R
AuCl3
O
R2
O
Cl3Au
R
R1
AuCl3
O
R2
R
O
AuCl3
R
Computational results:
AuCl3
R1
R2
R1
- DFT reveals same predicted Gibbs activation energy of 115 kJ/mol
for both AuI and AuIII
- Catalytic activities of AuCl3 and AuCl were indistinguishable within
the reliability of the chosen level of theory
Straub, B. F. Chem. Commun. 2004, 1726-1728
Asao, N.; Tokahashi, K.; Lee, L.; Kasahara, T.; Yamamoto, Y. J. Am. Chem. Soc. 2002, 124, 12650-12651
16
Hydration of Alkynes
- Hydration of alkynes is well-known however only electron-rich
acetylenes react satisfactorily
- Simple alkynes need toxic Hg(II) salts to enhance reactivity
R1
R2
+
(Ph3P)AuCH3 + acid
H2O
MeOH
O
R2
R1
1
R2
+ R1
O
2
Entry
R1
R2
Adduct
Yield
1
n-C4H9
H
1
99%
2
NC(CH2)3
H
1
83%
3
n-C3H7
CH3
1/2 = 1.2:1
76%
- Au has turnover frequencies of at least two orders of magnitude more
than other catalysts
- The major product is Markovnikov adduct
Mizushima, E.; Sata, K.; Hayashi, T., Tanaka,M.; Angew. Chem. Int. Ed. 2002,41, 4563
Fukuda, Y., Utimoto, K.; J. Org. Chem. 1991, 56, 3729
17
Acetylenic Schmidt Reaction
n-Bu
N3
(dppm)Au2Cl2 (2.5 mol %), AgSbF6 (5 mol %)
n-Bu
H
N
n-Bu
CH2Cl2
n-Bu
93%
N3
LAu
N
NH
H
R
R
R
N
N
N
AuL R
LAu
LAu
R
N2
R
N2
N N2
LAu
Gorin, D. J.; Davis, N. R.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 11260
R
18
Allene Activation
Br
catalyst
O
C8H17
Br
C8H17
O
toluene, rt
C8H17
+
Br
1
O
2
Entry
Catalyst
(1-2 mol%)
Solvent
(1M)
Temperature
(ºC)
Ratio
1:2
1
AuCl3
Toluene
0
88:12
2
AuCl3
Toluene
rt
95:5
3
AuCl3
Toluene
70
98:2
4
AuCl3
THF
rt
5:95
5
Au(PEt3)Cl
Toluene
rt
<1:99
Sromek, A. W.; Rubina, M.; Gevorgyan, V. J. Am. Chem. Soc. 2005, 127, 10500-10501
19
Proposed Mechanism
Br
Br
AuCl3
O
R
Au
Br
III
H
R
O
AuCl3
in toluene
Br
R
O
O
Cl3Au
R
Au(PEt3)Cl
AuI
Au
Au
Au
Br
R
O
Br
H
O
R
Sromek, A. W.; Rubina, M.; Gevorgyan, V. J. Am. Chem. Soc. 2005, 127, 10500-10501
H
Br
R
O
Br
O
20
Carbene-Like Intermediates
R3
OR
R1
+
Ph3PAuCl (5mol%), AgSbF6 (5mol %)
R4
MeNO2, rt
R2
R1 R2
R3
R4
RO
- Gold(I)-catalyzed cyclopropanation reaction tolerated a wide range of
olefin substitution
- The cis-cyclopropane is favored
- Concerted carbene transfer from a gold(I) –carbenoid intermediate
Entry
R
R1
R2
R3
R4
Yield
(cis:trans)
1
Pivaloate
Me
Me
Me
Me
67%
2
Acetate
H
TMSCH2
H
H
62%(1.3:1)
3
Benzoate
H
H
73%
Cyclohexyl
21
Johansson, M. J.; Gorin, D. J.; Staben, S. T.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 18002-18003
Carbene-Like Intermediates
- Identified DTBM-SEGPHOS-gold(I) ligand as the ligand of choice for
enantioselective olefin cyclopropanation reaction
O
(R)-DTBM-SEGPHOS
O
O
PAr'2
PAr'2
Ar'=
OMe
O
(R)-DTBM-SEGPHOS(AuCl)2 (2.5 mol%)
AgSbF6 (5 mol%)
OPiv
Ar
+
MeNO2, rt
Ar
= Ph
70 %, 81% ee
=
71%, 94% ee
Johansson, M. J.; Gorin, D. J.; Staben, S. T.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 18002-18003
Ar
OPiv
>20:1 cis:trans
22
Insight Into Mechanism
Ph
Ph
Path A
Ph
+
Ph
H
H
H
OAc
Ph
OAc
+ Au
L
Ph
O
Ph
L-Au
OAc
O
Au
L
Ph
Ph
Path B
- Large phosphine ligand
H
Ph

+
Ph
H
H
Au
L
OAc
Ph
OAc
+
increased selectivity for the cis cyclopropane
23
Johansson, M. J.; Gorin, D. J.; Staben, S. T.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 18002-18003
C-H Bond Activation
- Not as common as alkyne activation though more examples have been
emerging in the last few years
- Activates C-H bonds to create a nucleophile which can interact with
electrophiles
- Often there is a dual role of Au in these transformations
- Activates arenes
O
O
O
O
O
O
AuCl3 (5 mol%), AgOTf (15 mol%)
H
ClCH2CH2Cl
R
Au
R
R
- Spectroscopic and isotope labelling experiments indicate the
presence of the arene gold intermediate
Hoffmann-Roder, A.; Krause, N.; Org. Biomol. Chem. 2005, 3, 387-391
Shi, Z.; He, C.; J. Org. Chem. 2004, 69, 3669
24
Activation of β-Dicarbonyl Compounds
O
O
O
O
+
R
R
AuCl3 (5mol%), AgOTf (15mol%)
R2
R1
R
MeNO2, reflux
O
R
O
R
R1
O
R1
O
R
O
O
R
[AuI]
R
R2
R
[AuIII]
H
R
R2
R1
O
O
R
R
O
[AuIII]
R1
Yao, X.; Li, C. -J. J. Am. Chem. Soc. 2004, 126, 6884
R2
R2
R
R1
O
R
[AuIII] H
R2
25
2,3-Indoline-Fused Cyclobutanes
O
R2
O
AuCl(PPh3)/AgSbF6
O
R2
O
R1
N
R
CH2Cl2, rt
N H
R
R1
- Tandem cationic Au(I)-catalyzed activations of both propargylic
esters and the in situ generated allenylic esters
R2
OH
O
O
N
R
O
R1
O
R2
N
R
O
R1
R2
N AuL
R
R1
Product of first
catalytic cycle
26
Zhang, L. J Am. Chem. Soc. 2005, 127, 16804
2,3-Indoline-Fused Cyclobutanes
O
R2
O
O
AuCl(PPh3)/AgSbF6
R2
O
N
R
R1
CH2Cl2, rt
N H
R
R1
- Tandem cationic Au(I)-catalyzed activations of both propargylic
esters and the in situ generated allenylic esters
Entry
R
R1
R2
Yield
1
Me
(CH2)4CH3
Me
81%
2
H
Ph
Bu
98%
3
H
Ph
(CH2)3Br
95%
4
H
Ph
Ph
86%
27
Zhang, L. J Am. Chem. Soc. 2005, 127, 16804
Tandem Sequence
O
R2
O
R1
N
R
O
R2
Au(PPh3)
O
R1
N
R
Au(PPh3)
N
R
O
R2
O
Au(PPh3)
R1
R2
O
O
N
R
Zhang, L. J Am. Chem. Soc. 2005, 127, 16804
R1
28
O
Tandem Sequence
O
O
O
R1
O
N
R
R2 Au(PPh )
3
O
Au(PPh3)
O
Au(PPh3)
N R1
R
R2
O
R2
R2
R1
N
R
R1
O
N
R
O
Au(PPh3)
N
R
O
R2
O
Au(PPh3)
LAu
R2
R1
O
N
R
R1
O
R2
OH
O
O
N
R
Zhang, L. J Am. Chem. Soc. 2005, 127, 16804
N
R
O
R1
N H
R
R2
AuL
R1
R2
R1
29
First Enantioselective Example
RCHO
+
C
N
Au(s-HexNC)2+BF4-, L
CO2Me
CH2Cl2, rt
CO2Me
R
O
N
CO2Me
R
O
N
H Me
NMeCH2CH2NR2
L=
Fe PPh2
R = Me, Et
PPh2
Aldehyde
Ligand
R=
Yield
%
Ratio
trans/cis
% ee
of trans
PhCHO
Et
98
89/11
96
Me
91
90/10
94
Et
83
81/19
84
Me
97
80/20
87
Et
100
100/0
97
(E)-n-PrCH=CHCHO
t-BuCHO
Ito, Y.; Sawamura, M.; Hayashi, T. J. Am. Chem. Soc. 1986, 108, 6405-6406
Hayashi, T.; Sawamura, M.; Ito, Y. Tetrahedron 1992, 48, 1999
30
Control of Chirality
- When they created a catalyst with a longer side chain there was a loss
of stereoselectivity
- Without the terminal amino group there was a loss of stereoselectivity
- Other chiral phosphines gave racemic products
H
Ph Ph
P
O
R
Au
O
Fe
P
Ph
N
OMe
Ph
H
Me N
NHR2
Me
- Cu and Ag were much less selective than Au
- Medium size substituent on amino group gave higher trans/cis ratio
Hayashi, T.; Sawamura, M.; Ito, Y. Tetrahedron 1992, 48, 1999
Ito, Y.; Sawamura, M.; Hayashi, T.; J. Am. Chem. Soc. 1986, 108, 6405-6406
31
Enantioselective Hydrogenation
P
Au
(R,R) Me-Duphos
P
EtO2C
EtO2C
H
M-Duphos catalyst (0.1 mol%)
R
EtOH, rt, 4 atm of H2
Au
Pt
H
EtO2C
EtO2C
Cl
Au Cl
H
H
R
Ir
Substrate
TOF
ee (%)
TOF
ee (%)
TOF
ee (%)
R=H
3942
20
10188
3
8088
1
R=Ph
906
80
926
90
1110
26
R=2-Nf
214
95
250
93
325
68
1005
75
1365
15
1118
15
Ph
N
Ph
Gonzelez-Arrellano C.; Corma, A.; Iglesias, M.; Sanchez, F. Chem. Comm. 2005, 3451
32
Enantioselective hydrogenation
- Hydrogen activation by hydrogen splitting promoted by the electron-rich
Au-complex bearing heteroatoms (Cl).
R1
Ph
P Au Cl
Ph
H R1
Au
Ph P Ph
R2
R2
Ph
P Au
Ph
Ph
P Au H
Ph
R2
R1
HOEt
+
H H
*
HOEt
H2
Ph
P Au OEt
Ph
Gonzelez-Arrellano C.; Corma, A.; Iglesias, M.; Sanchez, F. Chem. Comm. 2005, 3451
R1
R2
*
33
Carene Terpenoids Synthesis
- Plant essential oil
- Is a pheromone
- Component of terebentine
- Is a [4.1.0] bicyclo compound that differs at the cyclopropane unit
H
H
H
H
H
H
2-carene
Sesquicarene
Isosesquicarene
34
Furstner, A.; Hannen, P. Chem. Commun. 2004, 2546-2547
Envisioned Strategy
H
R1
H
OAc
R1
R1
N2
O
O
-This specific type of rearrangement was discovered as a side reaction
mediated by ZnCl2
[M]
OAc
[M]
[M]
O
O
O
[M]
OAc
O
- Although PtCl2 is normally the catalyst of choice it resulted in a
significant amount of allenyl acetate
O
O
35
Furstner, A.; Hannen, P. Chem. Commun. 2004, 2546-2547
Sesquicarene Synthesis
O
OAc
1) HC CMgBr , THF, 0oC rt; 96%
AuCl3 (5 mol%)
1,2-dichloroethane
2) Ac2O, DMAP, Et3N 98%
Commercially available
geranyl acetone
Au
Au
O
O
O
O
H
H
Au
OAc
OAc
36
Furstner, A.; Hannen, P. Chem. Commun. 2004, 2546-2547
Sesquicarene Synthesis
H
H
LiAlH4
Et2O, 0°C rt
H
OAc
41% (over 2 steps)
H
L-Selectride
THF, -78°C rt
H
O
H
H
OH
93%
PPh3, DEAD, THF
70%
H
H
Sesquicarene
37
Furstner, A.; Hannen, P. Chem. Commun. 2004, 2546-2547
Can Be Applied to the Other Carenes
OAc
AuCl3 (5mol%)
1,2-dichloroethane
H
H
H
98%
AuCl3 (5mol%)
O
O
H
OAc
2-carene
H
H
1,2-dichloroethane
87%
H
OAc
H
Isosesquicarene
38
Furstner, A.; Hannen, P. Chem. Commun. 2004, 2546-2547
Jungianol
- Sesquiterpene isolated from Jungia Malvaefolia
- Isolated and characterized by Bohlmann et al. in 1977
- Possesses a trisubstituted phenol substructure and has two side
chains on the five membered, benzoannelated ring
OH
Proposed structure of Jungianol
Hashmi, A. S. K.; Ding, L.; Bats, J. W.; Fischer, P.; Frey, W. Chem. Eur. J. 2003, 9, 4339-4345
39
Key Step
O
O
OH
AuCl3 (2 mol%)
O
O
MeCN, 20oC
AuO
or
HO
OH
O
Hashmi, A. S. K.; Frost, T. M.; Bats, J. W. Org. Lett. 2001, 3, 3769-3771
Hashmi, A. S. K.; Frost, T. M.; Bats, J. W. J. Am. Chem. Soc. 2000, 122, 11553
OH
40
Synthesis
DMP
BrMgC CH
O
THF, -60°C
H
0°C
O
O
73%
AuCl3
CH2Cl2, 0°C
rt
O
O
77%
1) BrMgCH=C(CH3)2, THF, 0°C
CH3CN
75%
H
OH
2) silica gel
OH
O
O
96%
LiAlH4, h
Et2O, RT
OH
68%
Epi-Jungianol
OH
21%
Jungianol (revised structure)
Hashmi, A.S.K.; Ding,L.; Bats, J.W.; Fischer, P.; Frey, W. Chem. Eur. J. 2003, 9, 4339-4345
41
Conclusions
- Gold can catalyze reactions through Lewis acid activation
Nu
[Au]
Nu
Nu
[Au]
[Au]
- Au is able to activate C-H bonds to open a world of chemistry beyond
alkynes
- Aurated species now becomes a nucleophile instead of an
electrophile
- Development of ligands for enantioselective reactions
- Synthetically useful
42
Acknowledgements
Dr. Louis Barriault
 Patrick Ang
 Steve Arns
 Rachel Beingessner
 Christiane Grisé
 Mélina Girardin
 Roch Lavigne
 Louis Morency
 Maxime Riou
 Effie Sauer
 Guillaume Tessier
 Jeffrey Warrington
43