Synthesis of Bridged Bicyclic Amines by Intramolecular Amination of Remote C-H Bonds: Synergistic Activation by Light and Heat

Org Lett. 2020 Aug 21;22(16):6578-6583. doi: 10.1021/acs.orglett.0c02345. Epub 2020 Aug 10.

Abstract

The construction of complex aza-cycles is of interest to drug discovery due to the prevalence of nitrogen-containing heterocycles in pharmaceutical agents. Herein we report an intramolecular C-H amination approach to afford value-added and complexity-enriched bridged bicyclic amines. Guided by density functional theory and nuclear magnetic resonance investigations, we determined the unique roles of light and heat activation in the bicyclization mechanism. We applied both light and heat activation in a synergistic fashion, achieving gram-scale bridged aza-cycle synthesis.

Publication types

  • Research Support, Non-U.S. Gov't