β,β,β‐Trichloroethyl‐<i>N</i>H‐Enamine as Viable System for 5‐<i>Endo‐trig</i> Radical Cyclization <i>via</i> Multifaceted Cu^I−Cu^II Redox Catalysis: Single Step Synthesis of Multi‐Functionalized <i>N</i>H‐Pyrroles

Abstract

Abstract Here we report a mild and regioselective copper‐catalyzed direct synthesis of multi‐substituted and functionalized N H‐pyrroles in high yields from diverse β,β,β‐trichloroethyl ‐N H‐enamines via a novel 5‐ endo‐trig radical cyclization mode, previously known to be unviable in the enamine system. An approach to transform a geometrically ‘disfavored to favored’ 5‐ endo‐trig radical cyclization mode in N H‐enamine systems via multifaceted Cu I −Cu II redox catalysis generating radicals, preventing dehalogenative reduction of radical precursors and dehydrohalogenating the 5‐ endo‐trig cyclized products have been demonstrated experimentally. With wider substrate scope, this method incorporates halo‐, N H‐ and carbonyl functionalities besides alkyl, aryl and heteroaryl substituents in the pyrrole unit easily. These difficult to prepare 3‐halo‐ N H‐pyrroles are potential sources for natural products, agrochemicals, pharmaceuticals and organometallic chemistry. magnified image