gold-catalyzed reactions: a treasure trove of reactivity by: nathalie goulet march 9, 2006
TRANSCRIPT
Gold-Catalyzed Reactions:Gold-Catalyzed Reactions:A Treasure Trove of A Treasure Trove of
ReactivityReactivity
By: Nathalie GouletBy: Nathalie Goulet
March 9, 2006March 9, 2006
2
Overview- Introduction
- Reactivity of gold with alkynes
- Activation of allenes
- C-H bond activation
- Enantioselectivity
- Synthesis
- Carene terpenoids
- Jungianol
- Conclusions
3
Gold
- 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
- 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
Prices from Aldrich catalogue
5
Properties of Au: A Late Transition Metal
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
Pauling electronegativities of the transition elements
- 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
6
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+
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
Octahedral geometry
dz2dx2-y2
dyz dxz dxy
7
Why Are d8 Metals Square Planar?
dx2-y2
dxy
dz2
dxz dxz
dxy dyz dxz
dx2-y2 dz2
dx2-y2 dz2
dxy dyz dxz
Square Planar Octahedral 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
Crabtree, R. H., The 0rganometallic Chemistry of the Transition Metals, John Wiley & Sons, Inc, New York, 2001, p.46
AuX X
LXAuL X
Au(III): Au(I):
8
Lewis Acid ActivationHard 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
9
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
Toreki, R. http://www.ilpi.com/organomet/alkyne.html, 20/11/2003
Hashmi, A. S. K. Gold Bulletin, 2003, 36, 3-9
σ-type donation:
dx2-y2
dyz
dxz
dxy
Π-type back-donation:
Π-type donation:
δ-type back-donation:
10
Reactivity of Alkynes- Terminal alkynes can interact through a second mode of action
especially with AuI
- Forms a gold(I)-alkynyl complex
- stable
- will not readily react with nucleophiles
Hashmi, A. S. K., Gold Bulletin, 2003, 36, 3
Mingos, D. M. P.; Yau, J.; Menzer, S.; Williams, D. J. Angew Chem. Int. Ed. 1995, 34, 1894
RH
LAuX
base
RAuL
tBu
Au
tBu
η1-Au-η1: tBu
Au tBu
η2-Au-η1:
11
Reactivity of Alkynes
- 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
Nu [Au] Nu
[Au]
Nu
[Au]
12
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
OO
OLA
X
Sherry, B. D.; Toste, F. D. J. Am. Chem. Soc. 2004, 126, 15978-15979
13
Propargyl Claisen Rearrangement- Gold is so alkynophilic that it will prefer binding to the alkyne than to the
vinyl ether
Sherry, B. D.; Toste, F. D. J. Am. Chem. Soc. 2004, 126, 15978-15979
OR1
R2R3
[(Ph3PAu)3O] BF4 (1.0 mol%)CH2Cl2, rt
NaBH4, MeOH, rt
OH
R1
R2
R3
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%
O
Ph
[(Ph3PAu)3O] BF4 (1.0 mol%)CH2Cl2, 15 min, rt
NaBH4, MeOH, rt80%
OH
Ph
Hard LA or
Ph
O
14
Au
OR1
H
R
OR1
H
RAu
OH
R
R1
O H
R1R
H
[Au]
NaBH4OH
H
R
R1
Interaction of Gold with AlkynesO
R1
R2R3
[(Ph3PAu)3O] BF4 (1.0 mol%)CH2Cl2, rt
NaBH4, MeOH, rt
OH
R1
R2
R3
Sherry, B. D.; Toste, F. D. J. Am. Chem. Soc. 2004, 126, 15978-15979
15
Active Catalyst: AuI or AuIII
- AuCl3-catalyzed benzannulation by Yamamoto was studied using B3LYP, a DFT calculation method
- Reduction of high oxidation state pre-catalyst to catalyst is mandatory in several late transition state metal catalyzed reactions
- Many reactions can use either AuI or AuIII. Sometimes one is faster than the other, however the active catalyst remains unknown
Straub, B. F. Chem. Commun. 2004, 1726-1728Asao, N.; Tokahashi, K.; Lee, L.; Kasahara, T.; Yamamoto, Y. J. Am. Chem. Soc. 2002, 124, 12650-12651
H
R
Me
Me
O
R
AuCl3
O
+
16
Active Catalyst: AuI or AuIII
Computational results:
- 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
Yamamoto’s Proposal:
Straub, B. F. Chem. Commun. 2004, 1726-1728Asao, N.; Tokahashi, K.; Lee, L.; Kasahara, T.; Yamamoto, Y. J. Am. Chem. Soc. 2002, 124, 12650-12651
AuCl3 O
R
O
RAuCl3
O
R2
R1R
AuCl3
OR2
R1AuCl3
Cl3Au
O R
R1
R2
CHO
R
R2 R1
17
Hydration of Alkynes
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
- Hydration of alkynes is well-known however only electron-rich acetylenes react satisfactorily
- Simple alkynes need toxic Hg(II) salts to enhance reactivity
- Au has turnover frequencies of at least two orders of magnitude more than other catalysts
- The major product is Markovnikov adduct
R1 R2 + H2O(Ph3P)AuCH3 + acid
MeOH R1
O
R2R1
R2
O+
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%
1 2
18
Acetylenic Schmidt Reaction
Gorin, D. J.; Davis, N. R.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 11260
N3n-Bu
n-Bu
(dppm)Au2Cl2 (2.5 mol %), AgSbF6 (5 mol %)
CH2Cl2
93%
HNn-Bu n-Bu
LAu
N3
R
N
R
N2
AuL
N
RLAu
N2
N
RLAu
N
RH
NH
R
N2
N
RLAu
19
Allene Activation
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
Br
OC8H17
catalyst
toluene, rt OC8H17
Br+
OC8H17
Br1 2
20
Proposed Mechanism
Sromek, A. W.; Rubina, M.; Gevorgyan, V. J. Am. Chem. Soc. 2005, 127, 10500-10501
Br
OR
AuCl3Br
OR
AuCl3
Br
H
O
Cl3Au R
OR
Br
Au(PEt3)Cl
Br
OR
Au
OH
Br R
Au
O
Au
Br
H OR
Br
AuIII
AuI
in toluene
21
Carbene-Like Intermediates
Johansson, M. J.; Gorin, D. J.; Staben, S. T.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 18002-18003
- 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
ORR1
R2
R3
R4
RO
R1 R2
R4
R3
Ph3PAuCl (5mol%), AgSbF6 (5mol %)
MeNO2, rt+
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 Cyclohexyl H H 73%
22
Carbene-Like Intermediates
OPiv
Ar
(R)-DTBM-SEGPHOS(AuCl)2 (2.5 mol%)AgSbF6 (5 mol%)
MeNO2, rtAr
OPiv+
Ar = Ph 70 %, 81% ee
= 71%, 94% ee
>20:1 cis:trans
- Identified DTBM-SEGPHOS-gold(I) ligand as the ligand of choice for enantioselective olefin cyclopropanation reaction
PAr'2PAr'2
Ar'= OMe
O
O
O
O
(R)-DTBM-SEGPHOS
Johansson, M. J.; Gorin, D. J.; Staben, S. T.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 18002-18003
23
Insight Into Mechanism
- Large phosphine ligand increased selectivity for the cis cyclopropane
Path A
Path B
Au
Ph
OAc
L
Ph
L-Au
H
H
Ph
H
Ph
OAc
Au
L
H
H
H
Ph
Ph
OAc
Au
L
+
+
+
+
Ph
Ph
Ph
OAc
Ph
OAc
Ph
PhO
O
Johansson, M. J.; Gorin, D. J.; Staben, S. T.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 18002-18003
24
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
- 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
AuCl3 (5 mol%), AgOTf (15 mol%)
ClCH2CH2Cl
O O
R
H
O O
R
Au
O O
R
25
Activation of β-Dicarbonyl Compounds
Yao, X.; Li, C. -J. J. Am. Chem. Soc. 2004, 126, 6884
R
O O
RR1
R2+AuCl3 (5mol%), AgOTf (15mol%)
MeNO2, reflux
R R
R1R2
O O
R
O O
R
R1R2
R R
R1R2
O O [AuI]R
O O
R[AuIII]
H
R
O O
R
[AuIII] H
R2
R1
R
O O
R
[AuIII]
R1R2
26
2,3-Indoline-Fused Cyclobutanes
NR
O
O
R2
R1NR
OO
R1H
R2AuCl(PPh3)/AgSbF6
CH2Cl2, rt
- Tandem cationic Au(I)-catalyzed activations of both propargylic esters and the in situ generated allenylic esters
NR
OH
O
R2
R1
NR
O
OR2
R1
NR
OO
R1
R2
AuL
Product of first catalytic cycle
Zhang, L. J Am. Chem. Soc. 2005, 127, 16804
27
2,3-Indoline-Fused Cyclobutanes
NR
O
O
R2
R1NR
OO
R1H
R2AuCl(PPh3)/AgSbF6
CH2Cl2, rt
- 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%
Zhang, L. J Am. Chem. Soc. 2005, 127, 16804
28NR
O
O
R2
R1
NR
O
O
R2
R1
Au(PPh3)
NR
NR
O
OR2
R1
Au(PPh3)
O
OR2
Au(PPh3)
R1
Tandem Sequence
Zhang, L. J Am. Chem. Soc. 2005, 127, 16804
29
Tandem Sequence
NR
OH
O
R2
R1
NR
O
O
R2
R1
Au(PPh3)
NR
O
O
R2
Au(PPh3)
R1
NR
O
OR2
R1
NR
O
OR2
R1
Au(PPh3)
NR
O
OR2
R1Au(PPh3)
NR
O
OR2
LAu R1
NR
OO
R1H
R2
NR
OO
R1
R2
AuL
Au(PPh3)
Zhang, L. J Am. Chem. Soc. 2005, 127, 16804
30
First Enantioselective Example
Ito, Y.; Sawamura, M.; Hayashi, T. J. Am. Chem. Soc. 1986, 108, 6405-6406
Hayashi, T.; Sawamura, M.; Ito, Y. Tetrahedron 1992, 48, 1999
Aldehyde Ligand R=
Yield
%
Ratio trans/cis
% ee of trans
PhCHO Et 98 89/11 96
Me 91 90/10 94
(E)-n-PrCH=CHCHO Et 83 81/19 84
Me 97 80/20 87
t-BuCHO Et 100 100/0 97
RCHOAu(s-HexNC)2
+BF4-, L
CH2Cl2, rt ON
ON
R RCO2MeCO2Me
Fe PPh2
NMeCH2CH2NR2
MeH
PPh2
L=
R = Me, Et
CN CO2Me
+
31
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
Hayashi, T.; Sawamura, M.; Ito, Y. Tetrahedron 1992, 48, 1999
Ito, Y.; Sawamura, M.; Hayashi, T.; J. Am. Chem. Soc. 1986, 108, 6405-6406
AuP
P
FeN
O
OMe
HMe NMe NHR2
O R
HPh Ph
PhPh
- Cu and Ag were much less selective than Au
- Medium size substituent on amino group gave higher trans/cis ratio
32
Enantioselective Hydrogenation
Au Pt 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
(R,R) Me-Duphos
EtO2C
EtO2C
H
R
M-Duphos catalyst (0.1 mol%)
EtOH, rt, 4 atm of H2
HH
EtO2C RHEtO2C
P
P
Au ClAu Cl
PhN
Ph
Gonzelez-Arrellano C.; Corma, A.; Iglesias, M.; Sanchez, F. Chem. Comm. 2005, 3451
33
Enantioselective hydrogenation- Hydrogen activation by hydrogen splitting promoted by the electron-rich Au-complex bearing heteroatoms (Cl).
Gonzelez-Arrellano C.; Corma, A.; Iglesias, M.; Sanchez, F. Chem. Comm. 2005, 3451
PPh
PhAu Cl
H H
+
PPh
PhAu H
PPh PhAu
H R1 R2
PPh
PhAu
R2R1
*
PPh
PhAu OEt
R1 R2
R1 R2
*H2
HOEt
HOEt
34
Carene Terpenoids Synthesis
2-carene Sesquicarene Isosesquicarene
Furstner, A.; Hannen, P. Chem. Commun. 2004, 2546-2547
H
H
H
H
H
H
- Plant essential oil
- Is a pheromone
- Component of terebentine
- Is a [4.1.0] bicyclo compound that differs at the cyclopropane unit
35
Envisioned Strategy
-This specific type of rearrangement was discovered as a side reaction mediated by ZnCl2
Furstner, A.; Hannen, P. Chem. Commun. 2004, 2546-2547
H
H
R1O
N2
O
R1
R1
OAc
OAc[M]
O
O
O O[M] [M]
OAc
[M]
O
O
- Although PtCl2 is normally the catalyst of choice it resulted in a significant amount of allenyl acetate
36
O
Commercially available geranyl acetone
1) , THF, 0oC rt; 96%
2) Ac2O, DMAP, Et3N 98%
OAcAuCl3 (5 mol%)
1,2-dichloroethane
AuO
O
O OAu
AuOAc
OAc
HC CMgBr
H
H
Sesquicarene Synthesis
Furstner, A.; Hannen, P. Chem. Commun. 2004, 2546-2547
37
Sesquicarene Synthesis
Furstner, A.; Hannen, P. Chem. Commun. 2004, 2546-2547
OAc
H
H
LiAlH4
Et2O, 0°C rt
41% (over 2 steps) O
H
H
L-Selectride
THF, -78°C rt
93%OH
H
H
PPh3, DEAD, THF
70%
H
H
H
Sesquicarene
38
Can Be Applied to the Other Carenes
2-carene
Isosesquicarene
Furstner, A.; Hannen, P. Chem. Commun. 2004, 2546-2547
OAcAuCl3 (5mol%)
1,2-dichloroethane
98%H
H
OAcH
H
AuCl3 (5mol%)
1,2-dichloroethane
87% H
H
OAc H
HOO
39
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
Proposed structure of Jungianol
Hashmi, A. S. K.; Ding, L.; Bats, J. W.; Fischer, P.; Frey, W. Chem. Eur. J. 2003, 9, 4339-4345
OH
40
Key Step
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
O
O
OAuCl3 (2 mol%)
MeCN, 20oC
O
AuO
OHHO
OH
or
O
41
Synthesis
Hashmi, A.S.K.; Ding,L.; Bats, J.W.; Fischer, P.; Frey, W. Chem. Eur. J. 2003, 9, 4339-4345
OH O
BrMgC CH
THF, -60°C 0°C
73%
O H
OH
DMP
CH2Cl2, 0°C rt
77%
OO
AuCl3
CH3CN
75% OH O
1) BrMgCH=C(CH3)2, THF, 0°C
2) silica gel
96% O
LiAlH4, h
Et2O, RT
OH OH
68% 21%
Epi-Jungianol Jungianol (revised structure)
42
Conclusions- Gold can catalyze reactions through Lewis acid activation
- 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
Nu [Au] Nu
[Au]
Nu
[Au]