Coupling-isomerization-enamine addition-cyclocondensation sequences:: A multicomponent approach to substituted and annelated pyridines

Annelated (dihydropyridines, tetrahydroquinolines, naphthyridines) and substituted pyridines can be synthesized in moderate to good yields in a consecutive one-pot, four-component process by a coupling-isomerization-enamine addition-cyclocondensation sequence of an electron poor (hetero)aryl halide, a terminal propargyl alcohol, an enamine, and ammonium chloride. After the coupling-isomerization sequence a Diels-Alder reaction with inverse electron demand of the intermediate chalcone and the enamine furnishes a cycloadduct 6 that was unambiguously characterized by X-ray structure analysis as well as the 1,5-diketones 4b and 4g - the corresponding hydrolysis products and the pyridine derivatives 11e (dihydropyridine), 11i (tetrahydroquinoline), 11o (naphthyridine), and 14b and 14c (ethyl nicotinoates). Additionally, quantum chemical calculations support the stepwise nature of the enamine cycloaddition. (c) Wiley-VCH Verlag GmbH & Co. KGaA.