A Novel Aldol Condensation with 2-Methyl-4-pentenal and Its Application to an Improved Total Synthesis of Epothilone B.

The stabilization of the transition state through a favorable interaction between the double bond of 1 and the carbonyl group of 2 appears to be responsible for the high diastereoface selectivity of the aldol reaction. This key step in the highly concise total synthesis of epothilone B is followed by a Suzuki coupling to introduce the thiazole domain, a Noyori reduction to control the stereochemistry at C3, and a final macrolactonization (see reaction scheme). X=protecting group. © 1998 WILEY-VCH Verlag GmbH, Weinheim, Fed. Rep. of Germany.