C2-ketonylation of carbohydrates via excited-state palladium-catalyzed 1,2-spin-center shift.

ABSTRACT

C2-ketonyl-2-deoxysugars, sugars with the C2-hydroxyl group replaced by a ketone side chain, are important carbohydrate mimetics in glycobiology and drug discovery studies; however, their preparation remains a vital challenge in organic synthesis. Here we report the first direct strategy to synthesize this class of glycomimetics from readily available 1-bromosugars and silyl enol ethers via an excited-state palladium-catalyzed 1,2-spin-center shift (SCS) process. This step-economic reaction features broad substrate scope, has a high functional group tolerance, and can be used in late-stage functionalization of natural product- and drug-glycoconjugates. Preliminary experimental and computational mechanistic studies suggested a non-chain radical mechanism involving photoexcited palladium species, a 1,2-SCS process, and a radical Mizoroki-Heck reaction.