Direct Synthesis of α-Amino Nitriles from Sulfonamides via Base-Mediated C-H Cyanation

Org Lett. 2021 May 21;23(10):4018-4022. doi: 10.1021/acs.orglett.1c01232. Epub 2021 May 10.

Abstract

Herein, we disclose a transition-metal-free reaction system that enables α-cyanation of sulfonamides through C-H bond cleavage for the preparation of α-amino nitriles, including difficult-to-access all-alkyl α-tertiary scaffolds. More than 50 substrate examples prove a wide functional group tolerance. Additionally, its synthetic practicality is highlighted by gram-scalability and the late-stage modification of natural compounds. Mechanistic experiments suggest that this process involves in situ formation of an imine intermediate via base-promoted elimination of HF.

Publication types

  • Research Support, Non-U.S. Gov't