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Olefin Cross Metathesis Christopher Kendall March 20, 2006 The metathesis review: Handbook of Metathesis Grubbs, R. H., ed.; Wiley-VCH: Weinheim, 2003.

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Presentation on theme: "Olefin Cross Metathesis Christopher Kendall March 20, 2006 The metathesis review: Handbook of Metathesis Grubbs, R. H., ed.; Wiley-VCH: Weinheim, 2003."— Presentation transcript:

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 “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 "for the development of the metathesis method in organic synthesis" Yves ChauvinRobert H. GrubbsRichard R. Schrock

3 Commercial Metathesis

4 Articles cited on Web of Science, topic = “cross metathesis” Olefin Cross Metathesis (CM) review in Handbook of Metathesis by Chatterjee, A. K. (chapter 2.8, Vol. 2 pp ) review covering : Connon, S. J.; Blechert, S. Angew. Chem. Int. Ed. 2003, 42, 1900 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 ,  -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, Type I terminal olefins 1° allylic alcohols, amines (protected), esters allyl halides, silanes allyl boronate esters, phosphonates, phosphine oxides, sulfides styrenes (no large ortho groups) Type II 2° allylic alcohols, unptrotected 3° allylic alcohols acrylates, acrylamides, acrylic acid, acrolein, vinyl ketones vinyl epoxides perfluorinated alkane olefins styrenes (large ortho substituents) Type III 1,1-disubstituted olefins trisubstituted olefins (non-bulky) 4° allylic carbon 3° allylic alcohol (protected) vinyl phosphonates Type IV vinyl nitro olefins trisubstituted allylic alcohols (protected) For Grubbs II:

8 The functionalization of terminal olefins

9

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. Tetrahedron 2004, 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. Synthesis 2006, 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 Centrone, C. A.; Lowary, T. J. Org. Chem. 2002, 67, 8862 Rai, A. N.; Basu, A. J. Org. Chem. 2005, 70, 8228

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

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, steps

28 cm in natural product synthesis Crimmins, M. T.; Caussanel, F. J. Am. Chem. Soc. 2006, 128, steps (a) Grubbs II, CH 2 Cl 2, 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. Synthesis 2003, 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 One-pot cm/intramolecular cycloaddition Hodgson, D. M.; Angrish, D.; Labande, A. H. Chem. Commun. 2006, 627 Tandem ene-yne cm/[4 + 2]cycloaddition Mix, S.; Blechert, S. Org. Lett. 2005, 7, 2015

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, 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,  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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