Enantioselective Total Synthesis of the Marine Toxin (−)‐Gymnodimine Employing a Barbier‐Type Macrocyclization

Abstract

Sea the synthesis: At ambient temperature, tert-butyllithium promotes a Barbier-type macrocyclization in the first total synthesis of (−)-gymnodimine (Ts: toluene-4-sulfonyl; TBS: tert-butyldimethylsilyl), a member of the spirocyclic-imine family of marine toxins. The synthesis also features a vinylogous Mukaiyama aldol process to couple the labile butenolide moiety onto a macrocyclic ketone intermediate.