Microwave-Assisted, Co-Catalyzed Synthesis of Naphthyridines

Significance

A microwave-assisted, cobalt-catalyzed, inter- and intramolecular [2+2+2] cycloaddition reaction of open-chain alkyne nitriles to 5,6,7,8-tetrahydro-1,6-naphthyridines in good to excellent yields is reported. The intermolecular reaction is highly regioselective with preference for the formation of products with bulkier alkyne substituent adjacent to the ring nitrogen (R³) as evidenced from NOE studies. The starting material for the intermolecular reaction is readily prepared by either conjugate addition of propargylamine to acrylonitrile or a substitution reaction of propargyl­amine with α-bromo­acetonitrile. The precursor for the intermolecular cyclization was synthesized in four steps, starting from tosyl-protected N-methyl propargyl­amine.