Synthesis of 3- <i>epi</i> -Hypatulin B Featuring a Late-Stage Photo-Oxidation in Flow

Abstract

A synthesis of 3-<i>epi</i>-hypatulin B, a highly oxygenated and densely functionalized bicyclic scaffold, is reported. The carbon skeleton was prepared by functionalization of a cyclopentanone and an intramolecular Mukaiyama aldol reaction. Highlights include a late-stage photo-oxidation of a methoxyallene to provide an ester group. The problems encountered in the batch process were solved by translation into a flow protocol. Our synthesis highlights the value of flow chemistry to enable challenging late-stage transformations in natural product synthesis.