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Copper-Catalyzed Radical Relay 1,3-Carbocarbonylation across Two Distinct C═C Bonds

Nan‐Nan Dai, Yue-Jiao Lu, Zhong-Qi Wu, Yu Zhou, Ying Tong, Keqi Tang, Qiang Li, Jun‐Qi Zhang, Yu Liu, Wen‐Ting Wei

2024Organic Letters31 citationsDOI

Abstract

The radical relay provides an effective paradigm for intermolecular assembly to achieve functionalization across remote chemical bonds. Herein, we report the first radical relay 1,3-carbocarbonylation of α-carbonyl alkyl bromides across two separate C═C bonds. The reaction is highly chemo- and regioselective, with two C(sp 3 )–C(sp 3 ) bonds and one C═O bond formed in a single orchestrated operation. In addition, the synthesis method under mild conditions and using inexpensive copper as the catalyst allows facile access to structurally diverse 1,3-carbocarbonylation products. The plausible mechanism is investigated through a series of control experiments, including radical trapping, radical clock experiments, critical intermediate trapping, and 18 O labeling experiment.

Topics & Concepts

ChemistryRegioselectivityIntermolecular forceCatalysisAlkylRelaySurface modificationRadicalCopperTrappingCombinatorial chemistryPhotochemistryMoleculeOrganic chemistryPhysical chemistryPhysicsPower (physics)BiologyEcologyQuantum mechanicsCatalytic C–H Functionalization MethodsRadical Photochemical ReactionsSulfur-Based Synthesis Techniques