Photocatalytic generation of amidine carbon radicals for aminodihydroquinoline synthesis

Abstract

Amidines are ubiquitous in medicines and natural products. However, robust synthetic access to a broad spectrum of diverse analogues remains challenging due to the intrinsic limitations of the two-electron (2e) pathway. To overcome these synthetic constraints, we seek to develop a variant that generates amidine carbon radical as a common chemical synthon based on a one-electron (1e) pathway, remodeling retro-synthetical analysis for amidine-containing compounds. Herein, we present a mild, modular, and practical photocatalytic system tailored for assembling the highly privileged amidine pharmacophore. By ingeniously combining thiourea with PPh3, an amidine carbon radical is generated. This radical species can be efficiently coupled with a wide array of electron-deficient alkenes, establishing a highly adaptable platform for synthesizing an aminodihydroquinoline framework adorned with diverse substitution patterns. The efficacy and versatility of this method are demonstrated by approximately 50 examples, showcasing its broad applicability, efficiency, selectivity, and functional group compatibility.