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Gold-Catalyzed Reactions: A Treasure Trove of Reactivity

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. Gold.

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Gold-Catalyzed Reactions: A Treasure Trove of Reactivity

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  1. Gold-Catalyzed Reactions:A 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 • - 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 • 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 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 σ-type donation: Π-type donation: dxz dx2-y2 Π-type back-donation: δ-type back-donation: dyz dxy Toreki, R. http://www.ilpi.com/organomet/alkyne.html, 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 η1-Au-η1: η2-Au-η1: 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 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, 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

  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 Yamamoto’s 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 • 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 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 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 >20:1 cis:trans 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 β-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 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 Ito, Y.; Sawamura, M.; Hayashi, T. J. Am. Chem. Soc.1986, 108, 6405-6406 Hayashi, T.; Sawamura, M.; Ito, Y. Tetrahedron1992, 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. Tetrahedron1992, 48, 1999 Ito, Y.; Sawamura, M.; Hayashi, T.; J. Am. Chem. Soc.1986, 108, 6405-6406

  32. Enantioselective Hydrogenation (R,R) Me-Duphos 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

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