Carboalumination-Epoxide Ring Opening for the Formation of 1,4-Disubstituted (Z)-3,6-Alkadienols

Allylalumination of alkynes (i.e. forming Negishi's (Z)-alkenyl dialkylalane) followed by alkenylation of epoxides provides 1,4-disubstituted (Z)-3,6-alkadienols. The alkenylation can be facilitated by the presence of a neighbouring coordinating group in the epoxides. This one-pot approach has been successfully applied in the large-scale production of C10-C15 fragment of 9,10-didehydroepothilone D (a synthetic epothilone analog as an anti-cancer agent in phase 2 clinical trials).