Synthesis of Rapicone\nBased on Acyl Ketene–Alkyne\nCycloaddition

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