The Grubbs Reaction in Organic Synthesis: Part One of Three

We last reviewed organic synthesis applications of the Grubbs reaction on April 19, 2004. The (relatively) robust nature of the commercially-available catalyst and its commercial availability have spurred the expanding exploration of the scope of this reaction. Through this month, we will feature some recent highlights. (Part Two / Part Three)

The most straightforward application of the Grubbs reaction is to effect homologation of a terminal vinyl group. One concern with the use of the second generation Grubbs catalyst 3 is the cost, about $100/mmol. In conjunction with a total synthesis of the macrolide RK-397, Frank McDonald of Emory reported (J. Am. Chem. Soc. 2004, 126, 2495. DOI) that the conversion of 1 to 2 required 10 mol % of 3, but that it proceeded efficiently with just 2 mol % of the Hoveyda Ru catalyst 4 (J. Am. Chem. Soc. 2000, 122. 8168. DOI). The alkene so prepared was cleanly trans.

Because of the functional group tolerance of the Grubbs catalyst 3, it will operate even with complex substrates. In the course of a total synthesis of (-)-cytisine, Giordano Lesma and Alessandra Silvani of the University of Milan reported (Org. Lett. 2004, 6, 493. DOI) that 5 could be cyclized efficiently to 6.

The even more spectacular cyclization of 7 to Arenastatin A 8 was reported (Tetrahedron Lett. 2004, 45, 5309. DOI) by Gunda Georg of the University of Kansas. In this case, the catalyst used was the first generation Grubbs catalyst, 9.

Books written by Highlight Authors:

Douglass F. Taber

C. Oliver Kappe