Total Synthesis of (-)- and ent-(+)-4-Desacetoxy-5-desethylvindoline

Abstract

A concise synthesis of (-)- and ent-(+)-4-desacetoxy-5-desethylvindoline (2), a key analogue of vindoline, is disclosed enlisting an intramolecular tandem [4+2]/[3+2] cycloaddition cascade of 1,3,4-oxadiazole (5) to assemble the pentacyclic skeleton of 2 in a single step that forms three new rings, four C-C bonds, and sets all five key stereocenters. The subsequent efforts on the elaboration of 6 to 2 revealed two subtle features key to our recent total syntheses of vindoline, vindorosine, and related natural products based on this strategy.