Decarboxylative Grob-type fragmentations in the synthesis of trisubstituted Z olefins: application to peloruside A, discodermolide, and epothilone D

Abstract

Discriminating elimination: A new method for the synthesis of methyl-branched trisubstituted Z olefins, a structural motif in many polyketides with anticancer activity, relies on an (-)OH-induced decarboxylative Grob-type fragmentation (see scheme; Ms = mesyl). The starting materials are beta-mesyloxy lactones with a quaternary alpha center, which are prepared by aldol reactions in a diastereo- and enantioselective manner.