Multicomponent Reactions with Dihydroazines: Efficient Synthesis of a Diverse Set of Pyrido-Fused Tetrahydroquinolines

A multicomponent assembly of pyrido-fused tetrahydroquinolines is accomplished in a one-pot process from the interaction of dihydroazines, aldehydes, and anilines. A rational screening of the different components and parameters of this reaction, such as the range of reactive starting materials, catalysts and reaction conditions (solvent range; thermal, high pressure- and microwave-promoted processes) is carried out. Optimized conditions allow an efficient preparation of pyrido-fused tetrahydroquinolines with good yields, bypassing the biomimetic NADH-like reductive pathway which is typical in the interaction of dihydropyridines with carbonyl compounds and amines. Furthermore, solid-supported versions of the process have been developed, which should facilitate the preparation of libraries.