β,β,β‐Trichloroethyl‐NH‐Enamine as Viable System for 5‐Endo‐trig Radical Cyclization via Multifaceted CuI−CuII Redox Catalysis: Single Step Synthesis of Multi‐Functionalized NH‐Pyrroles

Abstract

AbstractHere we report a mild and regioselective copper‐catalyzed direct synthesis of multi‐substituted and functionalized NH‐pyrroles in high yields from diverse β,β,β‐trichloroethyl‐NH‐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 NH‐enamine systems via multifaceted CuI−CuII 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‐, NH‐ and carbonyl functionalities besides alkyl, aryl and heteroaryl substituents in the pyrrole unit easily. These difficult to prepare 3‐halo‐NH‐pyrroles are potential sources for natural products, agrochemicals, pharmaceuticals and organometallic chemistry.magnified image