Direct Construction of <i>C</i>‐Alkyl Glycosides from Non‐Activated Olefins via Nickel‐Catalyzed C(sp³)─C(sp³) Coupling Reaction

Abstract

Abstract Among C ‐glycosides, C ‐alkyl glycosides are significant building blocks for natural products and glycopeptides. However, research on efficient construction methods for C ‐alkyl glycosides remains relatively limited. Compared with Michael acceptors, non‐activated olefins are more challenging substrates and have rarely been employed in the construction of C ‐glycosides. Here, a highly efficient and convenient approach for the synthesis of C ‐alkyl glycosides through a nickel‐catalyzed C(sp 3 )‐C(sp 3 ) coupling reaction is presented. A distinctive feature of this method is its utilization of non‐activated olefins as the anomeric radical acceptors for hydroalkylation, allowing for the direct formation of C ‐glycoside bonds in a single step. Furthermore, this method demonstrates excellent compatibility with a broad scope of highly reactive functional groups. Mechanistic investigations suggest that the reaction proceeds via a free radical pathway, leading predominantly to the formation of products with α‐configuration. Overall, this innovative methodology offers a versatile and practical approach for the synthesis of C ‐alkyl glycosides, offering new avenues for the production of intricate glycosides with potential applications in drug discovery and chemical biology.