Synthesis of branched-chain sugars and higher-carbon sugars enabled by site-selective C–H alkylation relying on 1,5-hydrogen atom transfer of ethylenoxy radicals

Abstract

Rare branched-chain sugars and higher-carbon sugars are indispensable residues in many natural glycans of biological relevance. Isolation from natural sources and preparation by chemical synthesis are challenging for obtaining such constructs. We herein describe highly site-selective C–H allylation and alkylation of sugar rings as a promising and general protocol to access structurally unique branched-chain sugars and higher-carbon sugars. This strategy relies on the regioselective formation and the ensuing diverse functionalization of α-alkoxy-stabilized carbon-centered radicals which are generated by 1,5-hydrogen atom transfer of ethylenoxy radicals under mild reaction conditions. In addition, convenient removal of the directing group 2-hydroxyethylene moieties is achieved by a novel process. The synthetic potential of the developed method is demonstrated by the first efficient preparation of a shewanellose-based building block that is a typical example of uncommon branched-chain sugars.