Copper-Catalyzed Three-Component Synthesis of Polysubstituted Pyrroles

Significance

A synthesis of polysubstituted pyrroles is described. Starting from α-diazoketones, nitroalkenes, and amines, the three-component reaction proceeds under mild conditions to afford diverse tri- and tetrasubstituted 2-benzoyl pyrroles in moderate yields. A mechanism is suggested involving an NH insertion of carbene, a copper-catalyzed oxidative dehydrogenation of amine, and a [3+2] cycloaddition of azomethine ylide to an intermediate pyrrolidine (as evidence, pyrrolidine A was isolated and confirmed by X-ray crystal structure analysis), followed by thermal extrusion of HNO₂ and dehydrogenative aromatization to the pyrrole. However, this process failed for amines bearing alkyl and secondary amine groups in R⁴ position.