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Monday, January 19, 2009
Douglass F. Taber
University of Delaware

Alkene Metathesis: Synthesis of Panaxytriol (Lee), Isofagomine (Imahori and Takahata), Elatol (Stoltz), 5-F2t-Isoprostane (Snapper), and Ottelione B (Clive)

Alkene metathesis has been used to prepare more and more challenging natural products. The first and second generation Grubbs catalysts 1 and 2 and the Hoveyda catalyst 3 are the most widely used.

Daesung Lee of the University of Illinois at Chicago designed (Org. Lett. 2008, 10, 257. ) a clever chain-walking cross metathesis, combining 4 and 5 to make 6. The diyne 6 was carried on (3R, 9R, 10R)-Panaxytriol (7).

Tatsushi Imahori and Hiroki Takahata of Tohoku Pharmaceutical University found (Tetrahedron Lett. 2008, 49, 265. ) that of the several derivatives investigated, the unprotected alcohol 8 cyclized most efficiently. Selective cleavage of the monosubstituted alkene followed by hydroboration delivered the alkaloid Isofagomine (10).

Brian M. Stoltz of Caltech established (J. Am. Chem. Soc. 2008, 130, 810. ) the absolute configuration of the halogenated chamigrene Elatol 14 using the enantioselective enolate allylation that he had previously devised. A key feature of this synthesis was the stereocontrolled preparation of the cis bromohydrin.

Marc L. Snapper of Boston College opened (J. Org. Chem. 2008, 73, 3754 ) the strained cyclobutene 15 with ethylene to give the diene 16. Remarkably, cross metathesis with 17 delivered 18 with high regioselectivity, setting the stage for the preparation of the 5-F2t-Isoprostane (19).

Derrick L. J. Clive of the University of Alberta assembled (J. Org. Chem. 2008, 73, 3078. ) Ottelione B (26) from the enantiomerically-pure aldehyde 20. Conjugate addition of the Grignard reagent 21 derived from chloroprene gave the kinetic product 22, that was equilibrated to the more stable 23. Addition of vinyl Grignard followed by selective ring-closing metathesis then led to 26.

D. F. Taber, Org. Chem. Highlights 2009, January 19.