Solvent-controlled divergent (4 + 1) cycloaddition of 1,4-enynoates with amines: modular synthesis of pyrroles.

A metal-free, solvent-controlled chemodivergent (4 + 1) cycloaddition of hex-5-en-2-ynoates with primary amines for the modular assembly of tetrahydropyrroles and dihydropyrroles is reported. Simply switching between HFIP and DME enables selective access to two distinct pyrrolidine-type skeletons from identical starting materials under mild conditions. This transformation tolerates diverse functional groups and complex bio-relevant amine substrates, permitting late-stage skeleton diversification. Mechanistic studies reveal that solvent-modulated hydrogen-bonding interactions alter the cyclization pathway after aza-Michael addition, governing the observed chemoselectivity.