Catalytic Multicomponent Synthesis ofC‐Acyl Glycosides by Consecutive Cross‐Electrophile Couplings

C-Acyl glycosides are versatile intermediates to natural products and medicinally relevant entities. Conventional cross-coupling strategies to secure these molecules often relied on two-component manifolds in which a glycosyl precursor is coupled with an acyl donor (pre-synthesized or generated in situ) under transition metal or dual catalysis to forge a C-C bond. Here, we disclose a three-component Ni-catalyzed reductive regime that facilitates the chemoselective union of glycosyl halides, organoiodides and commercially available isobutyl chloroformate as a CO surrogate. The method tolerates multiple functionalities and the resulting products are obtained in high diastereoselectivities. Theoretical calculations provide a mechanistic rationale for the unexpectedly high chemoselectivity of sequential cross-electrophile couplings. This approach enables the expeditious assembly of difficult-to-synthesize C-acyl glycosides, as well as late-stage keto-glycosylation of oligopeptides.