Geometry-Controlled Synthesis of Pyrido/Pyrrolo-isoindolones via MHAT Radical Cyclization of Carbethoxy Methylene Isoindolone

A geometry-dependent intramolecular MHAT (metal-hydride hydrogen atom transfer) cyclization of olefins using carbethoxy methylene isoindolone as a radical acceptor has been developed for the synthesis of pyrroloisoindolone and pyridoisoindolone derivatives. The regioselectivity is dictated by the geometry of the substrate. While E-carbethoxy methylene isoindolones undergo selective 6-endo-trig HAT cyclization to afford pyrido[2,1-a]isoindolones, the corresponding Z-isomers favor 5-exo-trig cyclization, producing pyrrolo[2,1-a]isoindolones. The mechanistic understanding was further substantiated by control experiments.