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Ruthenium-Catalyzed Radical Cyclization/<i>meta</i>-Selective C–H Alkylation of Arenes via <i>σ-</i>Activation Strategy

Xue‐Ya Gou, Yuke Li, Yu‐Yong Luan, Wei‐Yu Shi, Cui‐Tian Wang, Yang An, Bo‐Sheng Zhang, Yong‐Min Liang

2021ACS Catalysis58 citationsDOI

Abstract

Free radical cyclization has emerged as one of the most important reaction types, which is widely used in natural product synthesis, pharmaceutical chemistry, and materials science. This report described the combination of radical cyclization and ruthenium-catalyzed meta-selective C–H functionalization for the synthesis of arylpyrrolidone derivatives. This method exhibited the highly meta-site selectivity of the primary, secondary, and tertiary alkyl radicals formed by intramolecular addition. A wide spectrum of directing groups bearing diversified N-heterocycles performed well, including biologically active molecules. Density functional theory calculations provided a theoretical basis for the high meta-selectivity and the favored reaction pathway of an intramolecular cyclization.

Topics & Concepts

ChemistryRutheniumIntramolecular forceCatalysisRadical cyclizationRadicalAlkylationSelectivityCombinatorial chemistryIntramolecular reactionMedicinal chemistryOrganic chemistryCatalytic C–H Functionalization MethodsRadical Photochemical ReactionsSulfur-Based Synthesis Techniques
Ruthenium-Catalyzed Radical Cyclization/<i>meta</i>-Selective C–H Alkylation of Arenes via <i>σ-</i>Activation Strategy | Litcius