Rapid Assembly of Tetrasubstituted Furans via Pummerer-Type Rearrangement

Abstract

Despite the many methods available for the synthesis of furans, few methods remain that allow for the custom-made assembly of fully substituted furans. Here we report a powerful protocol to rapidly construct tetrasubstituted, orthogonally functionalized furans under mild reaction conditions. The developed method involves the regioselective ring-opening of readily available 2,5-dihydrothiophenes followed by an oxidative cyclization to provide the heterocycle. The selective oxidation at sulfur is promoted by N-chlorosuccinimide as an inexpensive reagent and proceeds at ambient temperature in high yield within 30 min. The obtained furans serve as exceptionally versatile intermediates and were shown to participate in a series of valuable postmodifications. The fate of the initial sulfonium intermediate was investigated by mechanistic experiments, and computational studies revealed the existence of an unprecedented Pummerer-type rearrangement. The potential for organic synthesis is highlighted by the total synthesis of bisabolene sesquiterpenoids (pleurotins A, B, and D).