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Photoinduced and Copper-Catalyzed Asymmetric Alkylation of Glycine Derivatives via a Synergistic Electron/Atom Transfer Process

Qing‐Song Zhou, Yixuan Zhang, Jinlong Shang, Rupeng Qi, Xiaoyu Ren, Zhaoqing Xu, Chao Wang

2025ACS Catalysis11 citationsDOI

Abstract

As a fundamental building block for unnatural amino acids, photoinduced stereoselective functionalization at glycine’s C(sp 3 )–H bond provides a mild and effective route to synthesize aliphatic unnatural amino acids. Despite significant progress, developing alkylating reagents that avoid prefunctionalization and are readily available remains challenging. Herein, we report a photoinduced synergistic catalytic strategy merging single-electron transfer and atom transfer to efficiently achieve stereoselective cross-coupling between glycine derivatives and inactivated hydrocarbons or alkyl iodides. The key advantages of this strategy are 3-fold: 1) employing aryl sulfonium salts as aryl radical precursors demonstrates atom economy, with the additional benefits of straightforward synthesis and convenient recovery of raw materials; 2) the synergistic interplay between the photoreducing capability of dual-functional copper complexes and the atom-transfer proficiency of aryl radicals overcomes substrate redox potential limitations; and 3) the hydrogen atom abstraction capability of aryl radicals circumvents the requirement for strong external oxidants in conventional cross-dehydrogenative coupling reactions.

Topics & Concepts

ChemistryArylCombinatorial chemistryAlkylationRadicalHydrogen atomStereoselectivityCatalysisSubstrate (aquarium)AlkylReagentHydrogen atom abstractionPhotoinduced electron transferPhotochemistryGlycineAryl radicalSulfoniumEnantioselective synthesisOrganic synthesisOrganic chemistryPhotoredox catalysisAtom-transfer radical-polymerizationOrganocatalysisReaction mechanismRedoxIsoindolineElectron transferAtom economyReactive intermediateRadical Photochemical ReactionsCatalytic C–H Functionalization MethodsFluorine in Organic Chemistry
Photoinduced and Copper-Catalyzed Asymmetric Alkylation of Glycine Derivatives via a Synergistic Electron/Atom Transfer Process | Litcius