Rhodium-Catalyzed Regioselective Synthesis of Isoindolium Salts from 2-Arylpyridines and Alkenes in Aqueous Medium under Oxygen

A highly regioselective synthesis of pyrido[2,1-a]isoindolium salts from 2-arylpyridines and two equivalents of electron-deficient alkenes catalyzed by rhodium is demonstrated. The reaction was carried out in aqueous medium at 110 degrees C using inexpensive oxygen as oxidant. Reverse aza-Michael addition of the isoindolium salt occurs when the salt was treated with base to give a beta-disubstituted alkene product. A reaction mechanism involving an ortho C-H olefination of 2-arylpyridine by alkene, intramolecular aza-Michael addition, deprotonation at the beta-carbon of the alkene fragment followed by another Michael addition to give the final product is proposed.