Thermodynamic control synthesis of spiro[oxindole-3,3'-pyrrolines] via 1,4-dipolar cycloaddition utilizing imidazo[1,5- a]quinoline

Abstract

A series of novel 2-(quinolin-2-yl)-spiro[oxindole-3,3'-pyrrolines] were synthesized by one-pot three-component reaction involving dimethyl acetylenedicarboxylate, 1-phenylimidazo[1,5-a]quinoline and N-alkylisatins in chloroform at ∼60 °C for 24 h. Structures of these new spiro derivatives were deduced from HRMS and NMR spectral data. A plausible mechanism for the observed thermodynamic control pathway is presented herewith. Interestingly, the spiro adduct, derived from 5-chloro-1-methylisatin, exhibited excellent antiproliferative activity on MCF7, A549 and Hela human cell lines (IC₅₀ ≃ 7 μM).

Keywords: 1,4-dipolar cycloaddition; 1-phenylimidazo[1,5-a]quinolone; N-alkylisatins; dimethyl acetylenedicarboxcylate; kinetic versus thermodynamic control.