One-Pot C-H Arylation/Lactamization Cascade Reaction of Free Benzylamines

J Org Chem. 2020 May 15;85(10):6626-6644. doi: 10.1021/acs.joc.0c00542. Epub 2020 Apr 29.

Abstract

An efficient method has been developed for the synthesis of seven-membered biaryl lactams involving Pd-catalyzed, native amine-directed, ortho-arylation of benzylamines followed by in situ lactamization. This cascade sequence is enabled by the use of 2-iodobenzoates, which facilitates C-H arylation from the free amine under conditions that typically require an improved directing group approach. This reaction is characterized by a broad substrate scope with good functional group tolerance. The need for an ester versus carboxylic acid-functionalized coupling partner is also explored, as is the potential for synthesizing eight-membered biaryl lactams. Various applications are also investigated, including access to the aza-brassinolide core.

Publication types

  • Research Support, Non-U.S. Gov't