Gold-Catalyzed Reactions: A Treasure Trove of Reactivity

1
Gold-Catalyzed ReactionsA Treasure Trove of
Reactivity

• By Nathalie Goulet
• March 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

• 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

Prices from Aldrich catalogue
4
Gold
79
Au
196.97
http//www.molres.org/cgi-bin/pt-request
5
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
6
Crystal Field Theory
- d orbitals of a metal are affected by the
presence of ligands where the ligands act as a
negative charge
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
7
Why Are d8 Metals Square Planar?
dx2-y2
dx2-y2 dz2
dxy dyz dxz
dxy
dz2
dxy dyz dxz
dxz dxz
dx2-y2 dz2
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

Au(III)
Au(I)
Crabtree, R. H., The 0rganometallic Chemistry of
the Transition Metals, John Wiley Sons, Inc,
New York, 2001, p.46
8
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 p 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 p orbitals of the
  alkyne

s-type donation
?-type donation
dxz
dx2-y2
?-type back-donation
d-type back-donation
dyz
dxy
Toreki, R. http//www.ilpi.com/organomet/alkyne.ht
ml, 20/11/2003 Hashmi, A. S. K. Gold Bulletin,
2003, 36, 3-9
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

?1-Au-?1
?2-Au-?1
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
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

12
Propargyl Claisen Rearrangement
- Claisen rearrangement

• Can be catalyzed by
• Hard Lewis acids by coordination to the oxygen
  atom
• Soft Lewis acids by coordination to the p bond
• e.g. Hg(II) and Pd(II)

• Propargyl Claisen rearrangement
• Typical soft Lewis acids cannot be used

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

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
Sherry, B. D. Toste, F. D. J. Am. Chem. Soc.
2004, 126, 15978-15979
14
Interaction of Gold with Alkynes
Sherry, B. D. Toste, F. D. J. Am. Chem. Soc.
2004, 126, 15978-15979
15
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
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
Active Catalyst AuI or AuIII
Yamamotos Proposal

• 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

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
17
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
1
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 1.21 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
18
Acetylenic Schmidt Reaction
Gorin, D. J. Davis, N. R. Toste, F. D. J. Am.
Chem. Soc. 2005, 127, 11260
19
Allene Activation
1
2
Entry Catalyst (1-2 mol) Solvent (1M) Temperature (ºC) Ratio 12
1 AuCl3 Toluene 0 8812
2 AuCl3 Toluene rt 955
3 AuCl3 Toluene 70 982
4 AuCl3 THF rt 595
5 Au(PEt3)Cl Toluene rt lt199
Sromek, A. W. Rubina, M. Gevorgyan, V. J. Am.
Chem. Soc. 2005, 127, 10500-10501
20
Proposed Mechanism
Sromek, A. W. Rubina, M. Gevorgyan, V. J. Am.
Chem. Soc. 2005, 127, 10500-10501
21
Carbene-Like Intermediates

• 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 (cistrans)
1 Pivaloate Me Me Me Me 67
2 Acetate H TMSCH2 H H 62(1.31)
3 Benzoate Cyclohexyl Cyclohexyl H H 73
Johansson, M. J. Gorin, D. J. Staben, S. T.
Toste, F. D. J. Am. Chem. Soc. 2005, 127,
18002-18003
22
Carbene-Like Intermediates

• Identified DTBM-SEGPHOS-gold(I) ligand as the
  ligand of choice for enantioselective olefin
  cyclopropanation reaction

(R)-DTBM-SEGPHOS
Ar Ph 70 , 81 ee
71, 94 ee
gt201 cistrans
Johansson, M. J. Gorin, D. J. Staben, S. T.
Toste, F. D. J. Am. Chem. Soc. 2005, 127,
18002-18003
23
Insight Into Mechanism
Path A
Path B
- Large phosphine ligand increased
selectivity for the cis cyclopropane
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
25
Activation of ß-Dicarbonyl Compounds
Yao, X. Li, C. -J. J. Am. Chem. Soc. 2004, 126,
6884
26
2,3-Indoline-Fused Cyclobutanes
- Tandem cationic Au(I)-catalyzed activations of
both propargylic esters and the in situ
generated allenylic esters
Product of first catalytic cycle
Zhang, L. J Am. Chem. Soc. 2005, 127, 16804
27
2,3-Indoline-Fused Cyclobutanes
- 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
28
Tandem Sequence
Zhang, L. J Am. Chem. Soc. 2005, 127, 16804
29
Tandem Sequence
Zhang, L. J Am. Chem. Soc. 2005, 127, 16804
30
First Enantioselective Example
Aldehyde Ligand R Yield Ratio trans/cis ee of trans
PhCHO Et 98 89/11 96
PhCHO Me 91 90/10 94
(E)-n-PrCHCHCHO Et 83 81/19 84
(E)-n-PrCHCHCHO Me 97 80/20 87
t-BuCHO Et 100 100/0 97
Ito, Y. Sawamura, M. Hayashi, T. J. Am. Chem.
Soc. 1986, 108, 6405-6406 Hayashi, T. Sawamura,
M. Ito, Y. Tetrahedron 1992, 48, 1999
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

• 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
32
Enantioselective Hydrogenation
(R,R) Me-Duphos
Au Pt Ir
Substrate TOF ee () TOF ee () TOF ee ()
RH 3942 20 10188 3 8088 1
RPh 906 80 926 90 1110 26
R2-Nf 214 95 250 93 325 68
1005 75 1365 15 1118 15
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
34
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

2-carene
Sesquicarene
Isosesquicarene
Furstner, A. Hannen, P. Chem. Commun. 2004,
2546-2547
35
Envisioned Strategy

• This specific type of rearrangement was
  discovered as a side reaction mediated by ZnCl2

- Although PtCl2 is normally the catalyst of
choice it resulted in a significant amount of
allenyl acetate
Furstner, A. Hannen, P. Chem. Commun. 2004,
2546-2547
36
Sesquicarene Synthesis
Furstner, A. Hannen, P. Chem. Commun. 2004,
2546-2547
37
Sesquicarene Synthesis
Sesquicarene
Furstner, A. Hannen, P. Chem. Commun. 2004,
2546-2547
38
Can Be Applied to the Other Carenes
2-carene
Isosesquicarene
Furstner, A. Hannen, P. Chem. Commun. 2004,
2546-2547
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
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
41
Synthesis
Epi-Jungianol
Jungianol (revised structure)
Hashmi, A.S.K. Ding,L. Bats, J.W. Fischer, P.
Frey, W. Chem. Eur. J. 2003, 9, 4339-4345
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
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