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Gold-Catalyzed Reactions: A Treasure Trove of Reactivity By: Nathalie Goulet March 9, 2006.

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Presentation on theme: "Gold-Catalyzed Reactions: A Treasure Trove of Reactivity By: Nathalie Goulet March 9, 2006."— Presentation transcript:

1 Gold-Catalyzed Reactions: A Treasure Trove of Reactivity By: Nathalie Goulet March 9, 2006

2 2 Overview - Introduction - Reactivity of gold with alkynes - Activation of allenes - C-H bond activation - Enantioselectivity - Synthesis - Carene terpenoids - Jungianol - Conclusions

3 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. AuCl 3 5 : e.g. AuF 5 - Preconceived notion that gold is expensive ComplexPrice for 1 g$/molComplexPrice for 1 g$/mol AuCl197$45 786AuCl 3 170$ PtCl 2 260$69 160RhCl 3 260$ PdCl 2 95$11 144RuCl 3 97$ Prices from Aldrich catalogue

4 4 Gold Au

5 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 6 Crystal Field Theory - d orbitals of a metal are affected by the presence of ligands where the ligands act as a negative charge Crabtree, R. H., The 0rganometallic Chemistry of the Transition Metals, John Wiley & Sons, Inc, New York, 2001, p.46 Octahedral geometry dz2dz2 d x 2 -y 2 d yz d xz d xy

7 7 Why Are d 8 Metals Square Planar? d x 2 -y 2 d xy dz2dz2 d xz d xy d yz d xz d x 2 -y 2 d z 2 d xy d yz d xz Square PlanarOctahedralTetrahedral - The square planar geometry offers the electrons never to be placed in the highest energy orbital - d 10 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 Au(III):Au(I):

8 8 Lewis Acid Activation Hard Lewis acids: - small - high charge states - weakly polarizable - often activate reactions by coordination to the oxygen atom. - e.g. Ti 4+ and Fe 3+ Soft Lewis acids: - big - low charge states - strongly polarizable - often activate the reaction through coordination with the π bond - Cu + and Pd 2+ 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 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. 20/11/2003http://www.ilpi.com/organomet/alkyne.html Hashmi, A. S. K. Gold Bulletin, 2003, 36, 3-9 σ-type donation: d x 2 -y 2 d yz d xz d xy Π-type back-donation: Π-type donation: δ-type back-donation:

10 10 Reactivity of Alkynes - Terminal alkynes can interact through a second mode of action especially with Au I - 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 η 1 -Au-η 1 :η 2 -Au-η 1 :

11 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 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 π 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,

13 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, EntryR1R1 R2R2 R3R3 Yield 1p-MeO-C 6 H 4 Hn-C 4 H 9 89% 2p-CF 3 -C 6 H 4 HMe86% 3PhCH 2 CH 2 Me 91%

14 14 Interaction of Gold with Alkynes Sherry, B. D.; Toste, F. D. J. Am. Chem. Soc. 2004, 126,

15 15 Active Catalyst: Au I or Au III - AuCl 3 -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 Au I or Au III. Sometimes one is faster than the other, however the active catalyst remains unknown Straub, B. F. Chem. Commun. 2004, Asao, N.; Tokahashi, K.; Lee, L.; Kasahara, T.; Yamamoto, Y. J. Am. Chem. Soc. 2002, 124,

16 16 Active Catalyst: Au I or Au III Computational results: - DFT reveals same predicted Gibbs activation energy of 115 kJ/mol for both Au I and Au III - Catalytic activities of AuCl 3 and AuCl were indistinguishable within the reliability of the chosen level of theory Yamamotos Proposal: Straub, B. F. Chem. Commun. 2004, Asao, N.; Tokahashi, K.; Lee, L.; Kasahara, T.; Yamamoto, Y. J. Am. Chem. Soc. 2002, 124,

17 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, 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 EntryR1R1 R2R2 AdductYield 1n-C 4 H 9 H199% 2NC(CH 2 ) 3 H183% 3n-C 3 H 7 CH 3 1/2 = 1.2:176% 1 2

18 18 Acetylenic Schmidt Reaction Gorin, D. J.; Davis, N. R.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 11260

19 19 Allene Activation EntryCatalyst (1-2 mol%) Solvent (1M) Temperature (ºC) Ratio 1:2 1AuCl 3 Toluene088:12 2AuCl 3 Toluenert95:5 3AuCl 3 Toluene7098:2 4AuCl 3 THFrt5:95 5Au(PEt 3 )ClToluenert<1:99 Sromek, A. W.; Rubina, M.; Gevorgyan, V. J. Am. Chem. Soc. 2005, 127,

20 20 Proposed Mechanism Sromek, A. W.; Rubina, M.; Gevorgyan, V. J. Am. Chem. Soc. 2005, 127,

21 21 Carbene-Like Intermediates Johansson, M. J.; Gorin, D. J.; Staben, S. T.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 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 EntryRR1R1 R2R2 R3R3 R4R4 Yield (cis:trans) 1PivaloateMe 67% 2AcetateHTMSCH 2 HH62%(1.3:1) 3BenzoateCyclohexylHH73%

22 22 Carbene-Like Intermediates Ar= Ph70 %, 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 (R)-DTBM-SEGPHOS Johansson, M. J.; Gorin, D. J.; Staben, S. T.; Toste, F. D. J. Am. Chem. Soc. 2005, 127,

23 23 Insight Into Mechanism - Large phosphine ligand increased selectivity for the cis cyclopropane Path A Path B Johansson, M. J.; Gorin, D. J.; Staben, S. T.; Toste, F. D. J. Am. Chem. Soc. 2005, 127,

24 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, Shi, Z.; He, C.; J. Org. Chem. 2004, 69, 3669

25 25 Activation of β-Dicarbonyl Compounds Yao, X.; Li, C. -J. J. Am. Chem. Soc. 2004, 126, 6884

26 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 27 2,3-Indoline-Fused Cyclobutanes - Tandem cationic Au(I)-catalyzed activations of both propargylic esters and the in situ generated allenylic esters EntryRR1R1 R2R2 Yield 1Me(CH 2 ) 4 CH 3 Me81% 2HPhBu98% 3HPh(CH 2 ) 3 Br95% 4HPh 86% Zhang, L. J Am. Chem. Soc. 2005, 127, 16804

28 28 Tandem Sequence Zhang, L. J Am. Chem. Soc. 2005, 127, 16804

29 29 Tandem Sequence Zhang, L. J Am. Chem. Soc. 2005, 127, 16804

30 30 First Enantioselective Example Ito, Y.; Sawamura, M.; Hayashi, T. J. Am. Chem. Soc. 1986, 108, Hayashi, T.; Sawamura, M.; Ito, Y. Tetrahedron 1992, 48, 1999 AldehydeLigand R= Yield % Ratio trans/cis % ee of trans PhCHOEt9889/1196 Me9190/1094 (E)-n-PrCH=CHCHOEt8381/1984 Me9780/2087 t-BuCHOEt100100/097

31 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, Cu and Ag were much less selective than Au - Medium size substituent on amino group gave higher trans/cis ratio

32 32 Enantioselective Hydrogenation AuPtIr SubstrateTOFee (%)TOFee (%)TOFee (%) R=H R=Ph R=2-Nf (R,R) Me-Duphos Gonzelez-Arrellano C.; Corma, A.; Iglesias, M.; Sanchez, F. Chem. Comm. 2005, 3451

33 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 34 Carene Terpenoids Synthesis 2-carene SesquicareneIsosesquicarene Furstner, A.; Hannen, P. Chem. Commun. 2004, Plant essential oil - Is a pheromone - Component of terebentine - Is a [4.1.0] bicyclo compound that differs at the cyclopropane unit

35 35 Envisioned Strategy -This specific type of rearrangement was discovered as a side reaction mediated by ZnCl 2 Furstner, A.; Hannen, P. Chem. Commun. 2004, Although PtCl 2 is normally the catalyst of choice it resulted in a significant amount of allenyl acetate

36 36 Sesquicarene Synthesis Furstner, A.; Hannen, P. Chem. Commun. 2004,

37 37 Sesquicarene Synthesis Furstner, A.; Hannen, P. Chem. Commun. 2004, Sesquicarene

38 38 Can Be Applied to the Other Carenes 2-carene Isosesquicarene Furstner, A.; Hannen, P. Chem. Commun. 2004,

39 39 Jungianol - Sesquiterpene isolated from Jungia Malvaefolia - Isolated and characterized by Bohlmann et al. in 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,

40 40 Key Step Hashmi, A. S. K.; Frost, T. M.; Bats, J. W. Org. Lett. 2001, 3, Hashmi, A. S. K.; Frost, T. M.; Bats, J. W. J. Am. Chem. Soc. 2000, 122, 11553

41 41 Synthesis Hashmi, A.S.K.; Ding,L.; Bats, J.W.; Fischer, P.; Frey, W. Chem. Eur. J. 2003, 9, Epi-JungianolJungianol (revised structure)

42 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 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


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