Advancing Meta-Selective C-H Amination through Non-Covalent Interactions

J Am Chem Soc. 2024 Jan 24;146(3):1735-1741. doi: 10.1021/jacs.3c09904. Epub 2023 Dec 14.

Abstract

Regioselective C-H amination of simple arenes is highly desirable, but accessing meta-sites of ubiquitous arenes has proven challenging due to the lack of both electronic and spatial preference. This study demonstrates the successful use of various privileged nitrogen-containing functionalities found in pharmaceutical compounds to direct meta-C-H amination of arenes, overcoming the long-standing requirement for a redundant directing group. The remarkable advancements in functional group accommodation for precise regiochemical control were achieved through the discovery of an unprecedented organo-initiator and the strategic utilization of non-covalent interactions. This protocol has been successfully applied in the concise synthesis and late-stage derivatization of drug molecules, which would have been otherwise challenging to achieve.