Improved Synthesis of Epothilone B Employing Alkylation of an Alkyne for Assembly of Subunits

A strategy for assembling the two principal modules of epothilone B was developed that merges an allylic bromide with a terminal acetylene to fabricate the C10−C11 bond of the macrocycle. The resulting alkyne was semihydrogenated to give a seco ester previously employed in our total synthesis of epothilone B. This new approach affords a more efficient route to the naturally occurring macrolide and to its 9,10-dehydro analogue.