Enantioselective total synthesis of brevetoxin A: convergent coupling strategy and completion.

Abstract

A highly convergent, enantioselective total synthesis of brevetoxin A is reported. The development of a [X+2+X] Horner-Wadsworth-Emmons/cyclodehydration/reductive etherification convergent coupling strategy allowed a unified approach to the synthesis of two advanced tetracyclic fragments from four cyclic ether subunits. The Horner-Wittig coupling of the two tetracyclic fragments provided substrates that were explored for reductive etherification, the success of which delivered a late-stage tetraol intermediate. The tetraol was converted to the natural product through an expeditious selective oxidative process followed by methylenation.