Stereoselective Total Synthesis of Aspergillide A: A Visible Light-Mediated Photoredox Access to the Trisubstituted Tetrahydropyran Core.

Abstract

A stereoselective total synthesis of natural product aspergillide A is reported. The adopted strategy relies on the direct access to the key tetrahydropyran core through a visible light-mediated photoredox reaction from an allylic alcohol and iodoacetic acid. In a single manipulation, a γ-iodo-δ-valerolactone is obtained through an atom transfer radical addition (ATRA) followed by in situ acid-catalyzed lactonization. The obtained lactone possesses three functionalized sites, that were seized to link the required substituents in the final product and thus completing the total synthesis of aspergillide A.