Nitrogen-containing small polyfunctionalized heterocyclic molecules have gained great attention in the design of biologically active compounds in pharmaceutical industry. In contrast to the fully aromatized naphthyridines, which have shown significant bioactivities, tetrahydronaphthyridines have not received significant attention. Until recently, several 5,6,7,8-tetrahydro-1,6-naphthyridines have been reported as Mycobacterium Tuberculosis inhibitors. Another series of 5,6,7,8-tetrahydro-1,6-naphthyridine derivatives have been reported as potent HIV-1-integrase-allosteric-site Inhibitors. To probe the biological effects of this class of heterocycles, we have been interested in the synthesis of 5 ,6,7,8-tetrahydro-1,6-naphthyridines through microwave-promoted cobalt-catalyzed nitrile/alkyne [2+2+2] cyclization reactions. One intriguing feature noted in our microwave-promoted cyclization was the absence of alkyne trimerized byproducts, including both homotrimers and heterotrimers, even though it is well known that the CpCo(CO)2 catalyst readily promotes alkyne trimerization. Our research focused on investigation into the observed chemoselectivity of [2 + 2 + 2] cyclization favoring pyridine formation over alkyne trimerizations under microwave promotion. Furthermore, we studied the effect of the tethering atom such as nitrogen, carbon and oxygen of the reaction precursors. We strive to provide more insights into the microwave-promoted cobalt-catalyzed nitrile/alkyne [2+2+2] cyclization reactions.

Studies of chemoselectivity and tethering atom effect in microwave-promoted cobalt-catalyzed nitrile/alkyne [2+2+2] cyclization reactions towards the synthesis of 5,6,7,8-tetrahyro-1,6-naphthyridine

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