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. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)