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 <i>E</i>-carbethoxy methylene isoindolones undergo selective 6<i>-endo-trig</i> HAT cyclization to afford pyrido[2,1-<i>a</i>]isoindolones, the corresponding <i>Z</i>-isomers favor 5<i>-exo-trig</i> cyclization, producing pyrrolo[2,1-<i>a</i>]isoindolones. The mechanistic understanding was further substantiated by control experiments.