Acid-mediated intermolecular C–F/C–H cross-coupling of 2-fluorobenzofurans with arenes: synthesis of 2-arylbenzofurans

Abstract

Transition-metal-free acid-promoted biaryl construction was achieved via intermolecular C–F/C–H cross-coupling. By treating 2-fluorobenzofurans with arenes in the presence of AlCl₃, 2-arylbenzofurans were obtained. This protocol was successfully applied to the short-step orthogonal synthesis of a bioactive 2-arylbenzofuran natural product, which allows independent transformations of C–F and C–Br bonds. Mechanistic studies indicated that α-fluorine-stabilized carbocations, generated via the protonation of 2-fluorobenzofurans, served as key intermediates. The Friedel–Crafts-type C–C bond formation between the α-fluorocarbocations and arenes, followed by hydrogen fluoride elimination, afforded 2-arylbenzofurans.