Regio- and Diastereoselective Construction of Multisubstituted C-Vinyl Glycosides via Nickel-Catalyzed Three-Component Reaction of Alkynes

Abstract

C-vinyl glycosides are important carbohydrates with various biological activities and promising applications. However, the efficient synthesis of C-vinyl glycosides remains challenging, typically relying on two-component couplings of glycosyl donors with olefins or alkynes. These methods often involve air-sensitive organometallic reagents, directing groups, or activating group preactivation. Notably, the construction of multisubstituted C-vinyl glycosides directly from alkynes remains largely underexplored in synthetic carbohydrate chemistry. Here, a convenient and efficient method for the regio- and diastereoselective synthesis of multisubstituted C-vinyl glycosides via a nickel-catalyzed three-component reaction involving terminal alkynes, boronic acids, and glycosyl bromides in one pot is presented. This reaction proceeds by a radical pathway and demonstrates excellent regio- and diastereoselectivity, as evidenced by the α-selective, trans-addition products and the addition of the glycosyl moiety installed at the terminal position of the alkyne. This method utilizes commercially available starting materials without the need for additional preactivation, features a straightforward operational procedure, and demonstrates a broad substrate scope and functional group tolerance. Furthermore, this method is suitable for the late-stage glycosylation modification of complex natural products. Overall, this approach provides a widely applicable method to synthesize multisubstituted C-vinyl glycosides using simple and readily available three-component starting materials in one pot.