Carbon Dioxide-Mediated C( sp 2)-H Arylation of Primary and Secondary Benzylamines

J Am Chem Soc. 2019 May 15;141(19):7980-7989. doi: 10.1021/jacs.9b03375. Epub 2019 May 2.

Abstract

C-C bond formation by transition metal-catalyzed C-H activation has become an important strategy to fabricate new bonds in a rapid fashion. Despite the pharmacological importance of ortho-arylbenzylamines, however, effective ortho-C-C bond formation of free primary and secondary benzylamines using PdII remains an outstanding challenge. Presented herein is a new strategy for constructing ortho-arylated primary and secondary benzylamines mediated by carbon dioxide (CO2). The use of CO2 with Pd is critical to allowing this transformation to proceed under relatively mild conditions, and mechanistic studies indicate that it (CO2) is directly involved in the rate-determining step. Furthermore, the milder temperatures furnish free amine products that can be directly used or elaborated without the need for deprotection. In cases where diarylation is possible, an interesting chelate effect is shown to facilitate selective monoarylation.

Publication types

  • Research Support, Non-U.S. Gov't