Hydrogen Atom Transfer Enabled Acylsugars Synthesis via a Cooperative Copper and NHC Catalysis

Abstract

In this study, we report a direct acylation method for saccharides, achieved through the combination of copper and N-heterocyclic carbene (NHC) catalysis. This modular Cu/NHC dual-catalysis system exhibits excellent tolerance toward diverse functional groups and broad substrate applicability, enabling the efficient synthesis of a series of acylsugars, including derivatives bearing structurally complex natural product scaffolds and pharmacologically relevant motifs. To further validate the practical utility of this transformation, we successfully applied it to the potent modification of β-elemene, a naturally occurring molecule with well-documented antitumor activity. Additionally, preliminary mechanistic investigations and density functional theory (DFT) calculations provide compelling support for a radical coupling pathway underlying this reaction.