Copper-catalyzed remote nucleophilic substitution of 5-ethynylthiophene esters

Abstract

Here we demonstrate a strategy for the copper-catalyzed remote nucleophilic substitution of 5-ethynylthiophene esters at the η-position. The key to success lies in the design of an ethynyl group at the γ-position of thiophene, promoting the formation of a dearomative Cu–allenylidene species. This method features a broad range of C-, N-, O-, and S-nucleophiles, yielding a series of functionalized thiophene derivatives with excellent functional group tolerance under mild conditions. Facile late-stage transformations illustrate the potential practicality of this approach in organic synthesis.