Gold-Catalyzed Reactions: A Treasure Trove of Reactivity
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Transcript of Gold-Catalyzed Reactions: A Treasure Trove of Reactivity
Gold-Catalyzed Reactions:Gold-Catalyzed Reactions:A Treasure Trove of A Treasure Trove of
ReactivityReactivityBy: 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 $/molAuCl 197$ 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
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Gold
Au196.97
79
http://www.molres.org/cgi-bin/pt-request
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Properties of Au: A Late Transition Metal
Sc1.3
Ti1.5
V1.6
Cr1.6
Mn1.6
Fe1.8
Co1.9
Ni1.9
Cu1.9
Y1.2
Zr1.3
Nb1.6
Mo2.1
Tc1.9
Ru2.2
Rh2.3
Pd2.2
Ag1.9
La1.1
Hf1.3
Ta1.5
W2.3
Re1.9
Os2.2
Ir2.2
Pt2.3
Au2.5
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
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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
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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):
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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
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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:
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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
baseR
AuL
tBu
Au
tBu
η1-Au-η1: tBu
Au tBu
η2-Au-η1:
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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]
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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
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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
OHR1
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%
OHPh
Hard LA or
Ph
O
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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
OHR1
R2
R3
Sherry, B. D.; Toste, F. D. J. Am. Chem. Soc. 2004, 126, 15978-15979
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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
+
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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
OR2
R1R
AuCl3
OR2
R1AuCl3
Cl3Au
O R
R1
R2
CHO
R
R2 R1
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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
OR2
R1R2
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
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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
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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
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Proposed Mechanism
Sromek, A. W.; Rubina, M.; Gevorgyan, V. J. Am. Chem. Soc. 2005, 127, 10500-10501
Br
OR
AuCl3Br
OR
AuCl3
Br
H
OCl3Au R
OR
Br
Au(PEt3)Cl
Br
OR
Au
OH
Br R
Au
O
Au
Br
H OR
Br
AuIII
AuI
in toluene
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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
R3Ph3PAuCl (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%
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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
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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
AuL
H
H
H
Ph
Ph
OAc
AuL
+
+
+
+
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
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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
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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
R2R1
R
O O
R[AuIII]
R1R2
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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
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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
R1 Au(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 96Me 91 90/10 94
(E)-n-PrCH=CHCHO Et 83 81/19 84Me 97 80/20 87
t-BuCHO Et 100 100/0 97
RCHOAu(s-HexNC)2
+BF4-, L
CH2Cl2, rt O N O NR R
CO2MeCO2Me
Fe PPh2
NMeCH2CH2NR2
MeH
PPh2
L=
R = Me, Et
C N CO2Me
+
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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
PFe
NO
OMeHMe N
Me 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
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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 PhAuH R1 R2
PPh
PhAu
R2R1
*
PPh
PhAu OEt
R1 R2
R1 R2*
H2
HOEt
HOEt
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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
N2O
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
OO
OAuCl3 (2 mol%)
MeCN, 20oCO
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 HOH
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]
43
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