Phase-Transfer-Catalysed Synthesis of Pyrroloindolines and Pyridoindolines by a Hydrogen-Bond-Assisted Isocyanide Cyclization Cascade

A cascade reaction that generates pyrrolo‐ and pyridoindoline motifs from isocyanide precursors under phase‐transfer conditions is described. This transformation proceeds at room temperature in the presence of a quaternary ammonium catalyst and base to generate functionalized products containing an all‐carbon quaternary stereocentre. Quantum chemical calculations demonstrated that intramolecular general acid catalysis plays a key accelerating role through stabilization of developing charge in the transition state, and that the reaction is best described as a 5‐endo dig cyclization, rather than an anionic 6π electrocyclization. Investigations employing chiral phase‐transfer catalysts have given promising selectivities to date. Generating complexity: A cascade reaction that generates pyrrolo‐ and pyridoindoline motifs from isocyanide precursors under phase‐transfer conditions is described. Quantum chemical calculations demonstrated that intramolecular general‐acid catalysis plays a key accelerating role through stabilization of developing charge in the transition state, and that the reaction is best described as a 5‐endo‐dig cyclization, rather than an anionic 6π electrocyclization (see scheme).