Synthesis of 3-epi-Hypatulin B Featuring a Late-Stage Photo-Oxidation in Flow

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A total synthesis of 3-epi-hypatulin B, a highly oxygenated and densely functionalized bicyclic scaffold, is reported. The carbon skeleton was prepared by functionalization of a cyclopentanone core and an intramolecular Mukaiyama aldol reaction. The synthesis features a late-stage photo-oxidation of a methoxyallene intermediate for the installation of an ester functionality. Problems encountered during the batch process were solved by translation of the transformation into a flow protocol. Our synthesis highlights the value of flow chemistry to enable challenging steps in natural product synthesis.