Olefin Cross Metathesis

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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 Metathesis in total synthesis Nicolaou, K.
C. Bulger, P. G. Sarlah, D. Angew. Chem. Int.
Ed. 2005, 44, 4490
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The nobel prize in chemistry, 2005
"for the development of the metathesis method in
organic synthesis"
Considering the short time during which Grubbs
and Schrocks catalysts have been available, the
breadth of applications, is truly
remarkable. Prof. Per Ahlberg Nobel Committee
for Chemistry
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Commercial Metathesis
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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
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
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The mechanism
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The Catalysts
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The key reference Chatterjee, A. K. Choi, T.-L.
Sanders, D. P. Grubbs, R. H. J. Am. Chem. Soc.
2003, 125, 11360
For Grubbs II
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The functionalization of terminal olefins
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The functionalization of terminal olefins
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cm in natural product synthesis Wang, Y. Romo,
D. Org. Lett. 2002, 4, 3231
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cm in natural product synthesis Bouzbouz, S.
Cossy, J. Org. Lett. 2001, 3, 1451
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cm in natural product synthesis Bouzbouz, S.
Cossy, J. Org. Lett. 2001, 3, 1451
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cm in natural product synthesis Kitamura, T.
Sato, Y. Mori, M. Tetrahedron 2004, 60, 9649
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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
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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
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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
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Atom economy of cm vs. altenate reactions
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CM in pharmaceutical synthesis Pederson, R. L.
Fellows, I. M. Ung, T. A. Ishihara, H. Hajela,
S. P. Adv. Synth. Catal. 2002, 344, 728
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CM in pharmaceutical synthesis Hsu, M. C. Junia,
A. J. Haight, A. R. Zhang, W. J. Org. Chem.
2004, 69, 3907
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cm in natural product synthesis Chlor, R. B.
Nosse, B. Sörgel, S. Böhm, C. Seitz, M.
Reiser, O. Chem. Eur. J. 2003, 9, 260
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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
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Cm in library synthesis
Galan, M. C. OConner, S. E. Tetrahedron Lett.
2006, 47, 1563
Comin, M. J. Parrish, D. A. Deschamps, J. R.
Marquez, V. E. Org. Lett. 2006, 8, 705
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cm in natural product synthesis Statsuk, A. V.
Liu, D. Kozmin, S. A. J. Am. Chem. Soc. 2004,
126, 9546
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cm in natural product synthesis Albert, B. A.
Sivaramakrishnan, A. Naka, T. Koide, K. J. Am.
Chem. Soc. 2006, 128, 2792
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cm in natural product synthesis Ghosh, A. K.
Gong, G. J. Org. Chem. 2006, 71, 1085
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cm in natural product synthesis Wu, B. Liu, Q.
Sulikowski, G. A. Angew. Chem. Int. Ed. 2004, 43,
6673
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cm in natural product synthesis Yoshimura, T.
Fakushiji, F. Kondo, S. Wu, X. Shindo, M.
Shishido, K. Org. Lett. 2006, 8, 475
10 steps
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cm in natural product synthesis Crimmins, M. T.
Caussanel, F. J. Am. Chem. Soc. 2006, 128, 3128
(a) Grubbs II, CH2Cl2, reflux 68 10 Z isomer
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cm in complex molecule synthesis Lera, M. Hayes,
C. J. Org. Lett. 2001, 3, 2765
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cm in complex molecule synthesis Chen, G.
Schmieg, J. Tsuji, M. Franck, R. W. Org. Lett.
2004, 6, 4077
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cm in complex molecule synthesis Cho, Y. S. Wan,
Q. Danishefsky, S. J. Bioorg. Med. Chem. 2005,
13, 5259
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CM in Natural product modification Karama, U.
Höfle, G. Eur. J. Org. Chem. 2003, 1042
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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
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CM in Natural product structure
determination Tanaka, K. Nakanishi, K. Berova,
N. J. Am. Chem. Soc. 2003, 125, 10802
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Ene-yne cm review Diver, S. T. Giessert, A. J.
Synthesis 2003, 466
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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
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tandem cm reactions
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Tandem ene-yne cm/42cycloaddition 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
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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
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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
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Rom/cm/rcm Oikawa, M. Ikoma, M. Sasaki, M.
Tetrahedron Lett. 2005, 46, 5863
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cm in natural product synthesis ROM/CM/RCM Hart,
A. C. Phillips, A. J. J. Am. Chem. Soc. 2006,
128, 1094
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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
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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
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Alkyne cross metathesis Sashuk, V. Ignatowska,
J. Grela, K. J. Org. Chem. 2004, 69, 7748
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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
Full Story
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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
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Catalyst delivery vehicle in Cm Hansen, E. C.
Lee, D. Org. Lett. 2004, 6, 2035
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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
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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,