Arenethiolate-Catalyzed 1,5-HAT of Aryl Halides: Synthesis of γ-Spirolactams

Org Lett. 2024 Apr 19;26(15):3081-3085. doi: 10.1021/acs.orglett.4c00685. Epub 2024 Apr 3.

Abstract

γ-Spirolactam is a privileged building block that is found in a wide range of natural products and bioactive compounds. Herein, we report an arenethiolate-catalyzed 1,5-HAT of aryl halides to obtain γ-spirolactams through a SET reduction/intramolecular 1,5-HAT/cyclization/HAT process. This protocol features metal-free conditions and a broad substrate scope, furnishing the γ-spirolactams in moderate to excellent yields. Notably, aryl bromides, aryl chlorides and even aryl fluorides are well tolerated in this transformation. A mechanism involving arenethiolate as a SET catalyst is proposed based on DFT calculation.