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. 2024 Mar;11(12):e2307226.
doi: 10.1002/advs.202307226. Epub 2024 Jan 18.

Direct Construction of C-Alkyl Glycosides from Non-Activated Olefins via Nickel-Catalyzed C(sp3)─C(sp3) Coupling Reaction

Changyue Yu  1   2 , Yinghuan Xu  1   2 , Mingjie Zeng  3 , Jingjing Wang  1   2 , Wenhao Dai  1   2 , Jiang Wang  4 , Hong Liu  1   2   3
Affiliations

Direct Construction of C-Alkyl Glycosides from Non-Activated Olefins via Nickel-Catalyzed C(sp3)─C(sp3) Coupling Reaction

Changyue Yu et al. Adv Sci (Weinh). 2024 Mar.

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

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Conflict of interest statement

The authors declare no conflict of interest

Figures

Figure 1
Figure 1
Representative structures of C‐alkyl glycosides.
Scheme 1
Scheme 1
Metal‐catalyzed coupling reaction for the construction of C‐alkyl glycosides.
Scheme 2
Scheme 2
Gram‐scale synthesis, removal of the protecting groups, and synthetic applications.
Scheme 3
Scheme 3
Mechanistic studies and proposed reaction mechanism.
See this image and copyright information in PMC

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