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

A 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 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.

Automated summary

In this study, a synthesis of 3-epi-hypatulin B, a highly oxygenated and densely functionalized bicyclic scaffold, was reported. The carbon skeleton was prepared through functionalization of a cyclopentanone and an intramolecular Mukaiyama aldol reaction. Notably, a late-stage photo-oxidation of a methoxyallene was employed to provide an ester group. The translation of the batch process into a flow protocol successfully solved the problems encountered. This synthesis highlights the importance of flow chemistry in enabling challenging late-stage transformations in natural product synthesis.