A concise total synthesis of phytotoxic radulanin A facilitated by the photochemical ring expansion of a 2,2-dimethylchromene in flow

Abstract

The radulanins are biologically active bibenzyl natural products featuring a synthetically challenging 2,5-dihydro-1-benzoxepine core. In contrast with previous reports exhibiting lengthy strategies, we demonstrate the shortest synthesis of radulanin A to date, featuring a largely unexplored photochemical ring expansion reaction of a 2,2-dimethylchromene precursor. This work was adapted to a continuous flow setup for larger scale preparation, in view of biological investigations into the herbicidal properties of this natural product.

Total Synthesis of Phytotoxic Radulanin A Facilitated by the Photochemical Ring Expansion of a 2,2-Dimethylchromene in Flow

“…This reaction was however never exploited for synthetic purposes. Inspired by this work, we envisaged a deployment of this methodology as a late-stage molecular edit to afford radulanin A ( 1 ) from readily accessible 2,2-dimethylchromenes ( 3 ) and in flow (Figure c), which has resulted in the shortest and highest yielding total synthesis of 1 to date . Since radulanin A and the analogous 2,2-dimethylchromene are both natural products present in the liverworts, we suspect that this rearrangement may be of some biosynthetic significance. , Furthermore, this work allowed a larger-scale preparation of 1 for extended biological assays.…”