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Olefin Cross Metathesis Christopher Kendall March 20, 2006

Olefin Cross Metathesis Christopher Kendall March 20, 2006. The metathesis review: Handbook of Metathesis Grubbs, R. H., ed.; Wiley-VCH: Weinheim, 2003 Metathesis in total synthesis: Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew. Chem. Int. Ed. 2005 , 44 , 4490.

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Olefin Cross Metathesis Christopher Kendall March 20, 2006

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  1. Olefin Cross Metathesis Christopher Kendall March 20, 2006 The metathesis review: Handbook of Metathesis Grubbs, R. H., ed.; Wiley-VCH: Weinheim, 2003 Metathesis in total synthesis: Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew. Chem. Int. Ed.2005, 44, 4490

  2. The nobel prize in chemistry, 2005 Yves Chauvin Robert H. Grubbs Richard R. Schrock "for the development of the metathesis method in organic synthesis" “Considering the short time during which Grubbs’ and Schrock’s catalysts have been available, the breadth of applications, is truly remarkable.” Prof. Per Ahlberg Nobel Committee for Chemistry

  3. Commercial Metathesis

  4. Olefin Cross Metathesis (CM) review in Handbook of Metathesis by Chatterjee, A. K. (chapter 2.8, Vol. 2 pp. 246-295) review covering 1998-2002: Connon, S. J.; Blechert, S. Angew. Chem. Int. Ed.2003, 42, 1900 Articles cited on Web of Science, topic = “cross metathesis” Cross-metathesis methodologies have recently been shown to be highly effective in the synthesis of insect pheromones, polymer additives, and fine chemicals, i.e., valuable synthetic intermediates such as novel a,b-unsaturated carbonyl systems. Pederson, R. L. in Handbook of Metathesis Vol. 2 p 491

  5. The mechanism

  6. The Catalysts

  7. The key reference Chatterjee, A. K.; Choi, T.-L.; Sanders, D. P.; Grubbs, R. H. J. Am. Chem. Soc.2003, 125, 11360 Type I Type III terminal olefins 1° allylic alcohols, amines (protected), esters allyl halides, silanes allyl boronate esters, phosphonates, phosphine oxides, sulfides styrenes (no large ortho groups) 1,1-disubstituted olefins trisubstituted olefins (non-bulky) 4° allylic carbon 3° allylic alcohol (protected) vinyl phosphonates Type II Type IV 2° allylic alcohols, unptrotected 3° allylic alcohols acrylates, acrylamides, acrylic acid, acrolein, vinyl ketones vinyl epoxides perfluorinated alkane olefins styrenes (large ortho substituents) vinyl nitro olefins trisubstituted allylic alcohols (protected) For Grubbs II:

  8. The functionalization of terminal olefins

  9. The functionalization of terminal olefins

  10. cm in natural product synthesis Wang, Y.; Romo, D. Org. Lett.2002, 4, 3231

  11. cm in natural product synthesis Bouzbouz, S.; Cossy, J. Org. Lett.2001, 3, 1451

  12. cm in natural product synthesis Bouzbouz, S.; Cossy, J. Org. Lett.2001, 3, 1451

  13. cm in natural product synthesis Kitamura, T.; Sato, Y.; Mori, M. Tetrahedron2004, 60, 9649

  14. cm in natural product synthesis Randl, S.; Blechert, S. J. Org. Chem.2003, 68, 8879 Ghosh, A. K.; Liu, C. J. Am. Chem. Soc.2003, 125, 2374

  15. cm in natural product synthesis Spessard, S. J.; Stoltz, B. M. Org. Lett.2002, 4, 1943 Cossy, J.; Willis, C.; Bellosta, V.; Bouzbouz, S. J. Org. Chem.2002, 67, 1982

  16. cm in natural product synthesis Ferré-Filmon, K.; Delaude, L.; Demonceau, A.; Noels, A. F. Eur. J. Org. Chem.2005, 3319 Velder, J.; Ritter, S.; Lex, J.; Schmalz, H.-G. Synthesis2006, 273

  17. Atom economy of cm vs. altenate reactions

  18. CM in pharmaceutical synthesis Pederson, R. L.; Fellows, I. M.; Ung, T. A.; Ishihara, H.; Hajela, S. P. Adv. Synth. Catal.2002, 344, 728

  19. CM in pharmaceutical synthesis Hsu, M. C.; Junia, A. J.; Haight, A. R.; Zhang, W. J. Org. Chem.2004, 69, 3907

  20. cm in natural product synthesis Chlor, R. B.; Nosse, B.; Sörgel, S.; Böhm, C.; Seitz, M.; Reiser, O. Chem. Eur. J.2003, 9, 260

  21. Cm in library synthesis Plettenburg, O.; Mui, C.; Bodmer-Narkevitchy, V.; Wong, C.-H. Adv. Synth. Catal.2002, 344, 622 Rai, A. N.; Basu, A. J. Org. Chem.2005, 70, 8228 Centrone, C. A.; Lowary, T. J. Org. Chem.2002, 67, 8862

  22. Cm in library synthesis Galan, M. C.; O’Conner, S. E. Tetrahedron Lett.2006, 47, 1563 Comin, M. J.; Parrish, D. A.; Deschamps, J. R.; Marquez, V. E. Org. Lett.2006, 8, 705

  23. cm in natural product synthesis Statsuk, A. V.; Liu, D.; Kozmin, S. A. J. Am. Chem. Soc.2004, 126, 9546

  24. cm in natural product synthesis Albert, B. A.; Sivaramakrishnan, A.; Naka, T.; Koide, K. J. Am. Chem. Soc.2006, 128, 2792

  25. cm in natural product synthesis Ghosh, A. K.; Gong, G. J. Org. Chem.2006, 71, 1085

  26. cm in natural product synthesis Wu, B.; Liu, Q.; Sulikowski, G. A. Angew. Chem. Int. Ed.2004, 43, 6673

  27. cm in natural product synthesis Yoshimura, T.; Fakushiji, F.; Kondo, S.; Wu, X.; Shindo, M.; Shishido, K. Org. Lett.2006, 8, 475 10 steps

  28. cm in natural product synthesis Crimmins, M. T.; Caussanel, F. J. Am. Chem. Soc.2006, 128, 3128 8 steps (a) Grubbs II, CH2Cl2, reflux: 68% + 10% Z isomer

  29. cm in complex molecule synthesis Lera, M.; Hayes, C. J. Org. Lett.2001, 3, 2765

  30. cm in complex molecule synthesis Chen, G.; Schmieg, J.; Tsuji, M.; Franck, R. W. Org. Lett.2004, 6, 4077

  31. cm in complex molecule synthesis Cho, Y. S.; Wan, Q.; Danishefsky, S. J. Bioorg. Med. Chem.2005, 13, 5259

  32. CM in Natural product modification Karama, U.; Höfle, G. Eur. J. Org. Chem.2003, 1042

  33. CM in Natural product modification Smith III, A. B.; Rucker, P. V.; Brouard, I.; Freeze, S. B.; Xia, S.; Horwitz, S. B. Org. Lett.2005, 7, 5199

  34. CM in Natural product structure determination Tanaka, K.; Nakanishi, K.; Berova, N. J. Am. Chem. Soc.2003, 125, 10802

  35. Ene-yne cm review: Diver, S. T.; Giessert, A. J. Synthesis2003, 466

  36. Ene-yne cm Royer, F.; Vilain, C.; Elkaïm, L.; Grimaud, L. Org. Lett.2003, 5, 2007 Ene-yne cm in natural product synthesis Kummer, D. A.; Brenneman, J. B.; Martin, S. F. Org. Lett.2005, 7, 4621 stepwise: Evans, M. A.; Morken, J. P. Org. Lett.2005, 7, 3371

  37. tandem cm reactions

  38. Tandem ene-yne cm/[4+2]cycloaddition Mix, S.; Blechert, S. Org. Lett.2005, 7, 2015 One-pot cm/intramolecular cycloaddition Hodgson, D. M.; Angrish, D.; Labande, A. H. Chem. Commun.2006, 627

  39. Tandem cm in natural product synthesis Quinn, K. J.; Isaacs, A. K.; Arvary, R. A. Org. Lett.2004, 6, 4143 Michaelis, S.; Blechert, S. Org. Lett.2005, 7, 5513

  40. Rom/cm Mihovilovic, M. D.; Grötzl, B.; Kandioller, W.; Snajdrova, R.; Muskotál, A.; Bianchi, D. A.; Stanetty, P. Adv. Synth. Catal.2006, 348, 463 Weeresakare, G. M.; Liu, Z.; Rainer, J. D. Org. Lett.2004, 6, 1625

  41. Rom/cm/rcm Oikawa, M.; Ikoma, M.; Sasaki, M. Tetrahedron Lett.2005, 46, 5863

  42. cm in natural product synthesis: ROM/CM/RCM Hart, A. C.; Phillips, A. J. J. Am. Chem. Soc.2006, 128, 1094

  43. My favourite example: rom/cm/rcm Takao, K.; Yasui, H.; Yamamoto, S.; Sasaki, D.; Kawasaki, S.; Watanabe, G.; Tadano, K. J. Org. Chem.2004, 69, 8789

  44. Alkyne cross metathesis Fürstner, A.; Grela, K.; Mathes, C.; Lehmann, C. W. J. Am. Chem. Soc.2000, 122, 11799 Fürstner, A.; Mathes, C. Org. Lett.2002, 3, 221 review: Fürstner, A.; Davies, P. W. Chem. Commun.2005, 2307

  45. Alkyne cross metathesis Sashuk, V.; Ignatowska, J.; Grela, K. J. Org. Chem.2004, 69, 7748

  46. Asymmetric cm Van Veldhuizen, J. J.; Garber, S. B.; Kingsbury, J. S.; Hoveyda, A. H. J. Am. Chem. Soc.2002, 124, 4954 Gillingham, D. G.; Kataoka, O.; Garber, S. B.; Hoveyda, A. H. J. Am. Chem. Soc.2004, 126, 12288 • Schrock, R. R.; Hoveyda, A. H. Angew. Chem. Int. Ed.2003, 42, 4592 • Shawn Collins, Literature Meeting, October 4, 2004 Full Story:

  47. Cm improvement: catalyst loading Forman, G. S.; Tooze, R. P. J. Organomet. Chem.2005, 690, 5863 Check Forman 2005 Organomet page ?? Cm improvement: reaction time Bargiggia, F. C.; Merray, W. V. J. Org. Chem.2005, 70, 9636

  48. Catalyst delivery vehicle in Cm Hansen, E. C.; Lee, D. Org. Lett.2004, 6, 2035

  49. A temporary silicon-tethered rcm Evans, P. A.; Cui, J.; Gharpure, S. J.; Polosukhin, A.; Zhang, H.-R. J. Am. Chem. Soc.2003, 125, 14702

  50. summary • Cross Metathesis increasingly used as disconnection late in natural product total synthesis • Useful tool for library synthesis, especially in biochemical-type applications • “Ideal” reaction: a catalytic method for a highly efficient (re: atom economy) C-C bond forming reaction • Improvement still possible in catalyst loading, stoichiometry, reaction time/temperature, selectivity, …

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