Pd-catalyzed stereoretentive synthesis of reversed C-acyl glycosides: access to rare l-sugars and higher-carbon sugars.

Reversed C-acyl glycosides represent a versatile class of nonclassical glycosides with potential in complex carbohydrate synthesis, including l-sugars, higher-carbon sugars, and medicinal chemistry. Conventional strategies for l- and higher-carbon sugars are limited by multi-step protection-deprotection sequences and poor stereocontrol. Herein, we report a general Pd-catalyzed reversed acyl C-glycosylation that efficiently couples configurationally stable reversed glycosyl stannanes with C(sp2)- and C(sp3)-derived thioesters under mild conditions. The reaction proceeds with complete stereoretentive transfer, enabling precise access to both d- and l-type glycosides, including higher-carbon sugar derivatives and C-ferrocenecarbonyl glycosides. The broad substrate scope, excellent functional group tolerance, and predictable stereochemical outcome highlight the robustness and synthetic versatility of this approach. Applications of the resulting reversed C-acyl glycosides as chiral synthons enable d-to-l interconversion, construction of l-sugar analogues, and derivatization toward designer carbohydrate frameworks. Importantly, this transformation enables a distinct d-to-l conversion featuring simultaneous C4 and C5 inversion, unlike conventional methods that modify only C5 configuration. Overall, this protocol establishes a general platform for stereocontrolled construction and diversification of structurally defined nonclassical glycosides, providing a foundation for glycodiversification, complex sugar synthesis, and exploration of biologically relevant C-glycosyl scaffolds.