Synthesis of N-Heteroaromatic Compounds through Cyclocarbonylative Sonogashira Reactions

A protocol based on cyclocarbonylative Sonogashira reactions has been developed for the synthesis of nitrogen-containing heterocycles. The process is carried out under CO pressure, in the presence of a small amount of PdCl2(PPh3)2 (0.2–0.4 mol-%) as a catalytic precursor, and without the need for a copper salt as cocatalyst. Suitable tosylamides reacted successfully with iodoarenes bearing electron-withdrawing and electron-donating groups. In particular, N-(2-ethynylbenzyl)-4-methylbenzenesulfonamide gave carbonylmethylene isoindolines with complete chemo- and stereoselectivity. On the other hand, the reaction between iodoarenes and N-(2-ethynylphenethyl)-4-methylbenzenesulfonamide did not yield tetrahydroisoquinolines as expected, but dihydrobenzoazepines were obtained.