康 · 学术 | Reaction of the Day No. 991

The Merger of Aryl Radical-Mediated Halogen-Atom Transfer (XAT) and Copper Catalysis for the Modular Cross-Coupling Type Functionalization of Alkyl Iodides

Lewis Caiger, Huaibo Zhao, Timothée Constantin, James J. Douglas, and Daniele Leonori

Institute of Organic Chemistry, RWTH Aachen University, 52056 Aachen, Germany; Department of Chemistry, University of Manchester, Manchester M13 9PL, U.K.; Early Chemical Development, Pharmaceutical Sciences R&D, AstraZeneca, Macclesfield SK10 2NA, U.K.

—ACS Catal. 2023, 13, 4985−4991.

Recommended by Xuemei Yao _ MC3

KEYWORDS: halogen-atom transfer, copper catalysis, cross-coupling, aryl radicals, alkyl iodide

ABSTRACT: Here, we report a toolbox strategy to cross-couple unactivated secondary alkyl iodides with various N-, O-, and C based nucleophiles. This strategy harnesses the ability of photoredox-generated phenyl radicals to mediate halogen-atom transfer (XAT) and convert alkyl iodides into the corresponding radicals. These species engage in a second catalytic cycle, mediated by copper, which enables C−N/O/C bond formation with the various nucleophiles.

Reaction Scope

Proposed Mechanism

Summary and Comments

The results reported here demonstrate that aryl radical-mediated XAT can be effectively used, in conjunction with copper catalysis, for the divergent and modular assembly of C(sp³)−N/O/C bonds using alkyl iodide as the coupling partners. This strategy provides access to XAT−Cu reactivity without the need for expensive or potentially hazardous reagents and delivers products in a manner orthogonal to classic but still challenging palladium and nickel catalysis.

Prof. D. Leonori报道了，芳基自由基介导的XAT可以有效地与铜催化相结合，催化烷基碘化物与亲和试剂偶联形成C(sp³)−N/O/C键。该策略无需昂贵或潜在危险的试剂即可获得XAT−Cu反应性，对传统但仍然具有挑战性的钯和镍催化体系是一种很好的补充。