Synthesis of Rapicone Based on Acyl Ketene–Alkyne Cycloaddition

We report herein a concise route for the total synthesis of rapicone. The key strategy to form the ynone intermediate involves an Fe(III)/TEMPO-catalyzed aerobic oxidation of a 1,3-dihydroisobenzofuran moiety. This ether oxidation for the simultaneous installation of the keto aldehyde allowed the effective formation of the required ynone intermediate. The concise total synthesis of rapicone is substantiated by the unique formal [4 + 2] cycloaddition of acyl ketene with alkynone and is completed in 7 steps with 9.4% overall yield.