Copper-Catalyzed Cascades Enable Fused Pyrroles with Tunable Ring Sizes.

A novel route for the preparation of fused pyrroles with tunable ring sizes is presented as a copper-catalyzed tandem [3+2] cyclization/Ullmann coupling. This protocol established a versatile and general platform for the controllable synthesis of fused pyrrole architectures, which is particularly suitable for the efficient construction of challenging medium-sized and macrocyclic fused pyrrole systems. Mechanistic investigations and control experiments revealed that the copper catalyst served a triple functional role throughout the transformation: as a Lewis acid to trigger propargyl-allenyl isomerizations, as a catalytic hub to orchestrate ordered isocyanide insertions, and as a mediator of Ullmann-type coupling through an intramolecular N-arylation pathway. In addition, isocyanide acted concurrently as a C1 and C1N1 synthon, enabling the first unified implementation of imidoylation, cyanation, and ketenimination within a single [3+2] cyclization. Significantly, the synthetic utilities were further highlighted through late-stage modification of pharmaceutical molecules, formal syntheses of antipsychotic drug FPPQ, and potent antibacterial activity against Escherichia coli and Staphylococcus aureus.