Direct Construction of C‐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(sp3)‐C(sp3) 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.

Keywords

• C‐alkyl glycosides
• C(sp3)─C(sp3) coupling
• non‐activated olefins
• nickel catalysis