A Combined Vinylogous Mannich/Diels–Alder Approach for the Stereoselective Synthesis of Highly Functionalized Hexahydroindoles

A versatile strategy for the formation of hydroindole derivatives is reported. The molecules synthesized are highly functionalized and bear up to six stereogenic centers. We were able to develop a stereoselective route starting from nonchiral commercially available materials. Key steps in the formation of the bicyclic products are an organocatalytic vinylogous Mukaiyama–Mannich and a Diels–Alder reaction. The former uses a 1,1′-bi-2-napthol (BINOL)-based chiral Bronsted acid catalyst to build the first stereogenic center. The [4+2] cycloaddition proceeds highly diastereoselectively and furnishes one main stereoisomer, which represents the scaffold of the mycotoxins Rostratin B–D. Other transformations include iodolactonization, a Curtius rearrangement, additions, oxidations, and reductions.