Publication

Abstract : Here 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.