期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2020
卷号：117
期号：35
页码：21058-21064
DOI：10.1073/pnas.2011831117
出版社：The National Academy of Sciences of the United States of America
摘要：The copper-catalyzed arylation of unsaturated nitrogen heterocycles, known as the Ullmann–Goldberg coupling, is a valuable transformation for medicinal chemists, providing a modular disconnection for the rapid diversification of heteroaromatic cores. The utility of the coupling, however, has established limitations arising from a high-barrier copper oxidative addition step, which often necessitates the use of electron-rich ligands, elevated temperatures, and/or activated aryl electrophiles. Herein, we present an alternative aryl halide activation strategy, in which the critical oxidative addition (OA) mechanism has been replaced by a halogen ion–radical capture (HARC) sequence that allows the generation of the same Cu(III)-aryl intermediate albeit via a photoredox pathway. This alternative mechanistic paradigm decouples the bond-breaking and bond-forming steps of the catalytic cycle to enable the use of many previously inert aryl bromides. Overall, this mechanism allows access to both traditional C–N adducts at room temperature as well as a large range of previously inaccessible Ullmann–Goldberg coupling products including sterically demanding ortho -substituted heteroarenes.
关键词：photoredox catalysis ; C–N coupling ; halogen atom abstraction
