Rapid Assembly of Tetrasubstituted Furans via Pummerer-Type Rearrangement

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).

Automated summary

A powerful method for the synthesis of tetrasubstituted furans has been developed, involving the regioselective ring-opening of 2,5-dihydrothiophenes followed by an oxidative cyclization. The potential for organic synthesis is highlighted by the total synthesis of bisabolene sesquiterpenoids using the obtained furans. Mechanistic experiments and computational studies revealed an unprecedented Pummerer-type rearrangement in the reaction process.