Visible light induced palladium-catalyzed Suzuki–Miyaura cross-coupling of glycosyl chlorides to form C-aryl glycosides

Abstract

Both natural and mimetic C-aryl glycosides exhibit diverse biological activities and play significant roles in drug design. Despite various methods having been developed for the synthesis of C-aryl glycosides, the Suzuki–Miyaura reaction of glycosyl chlorides to form anomeric C-aryl glycosides (Csp³–Csp² coupling) has not been reported due to the challenging oxidative addition of a transition metal to the C–Cl bond. Herein, we present a simple and powerful method utilizing excited-state palladium-catalyzed Suzuki–Miyaura cross-coupling to synthesize C-aryl glycosides (Csp³–Csp²). This method can be applied to a wide range of aryl and heteroaryl boronic ester substrates as well as glycosyl chlorides. A variety of C-aryl pyranosides and furanosides can be synthesized in a straightforward manner. Furthermore, it provides a tool for the late-stage modification of more complex drug molecules.