Evaluation of the reaction mechanism between 1,4-dihydropyridines and α,β-unsaturated nitriles.

Hydride transfer reactions involving 1,4-dihydropyridines play a central role in bioorganic chemistry as they represent an important share of redox metabolism. For this class of reactions, the direct hydrid transfer is the commonly accepted mechanism, however an Alder-Ene-like pathway has been proposed as a plausible alternative. The reaction between 1,4-ditrimethylsilyl-1,4-dihydropyridine, and α,β-unsaturated nitriles is a solid candidate for this latter pathway. In this work, we perform high level ab initio and density functional theory computations to characterize the mechanism of this reaction, taking into account diverse reaction paths, evaluating the effect of solvent polarity and variations in chemical structure. Our analysis explains the stereochemical aspects of the reaction, characterizing the detected but up to now unidentified predominant products. The reactions are found to proceed in a highly asynchronous, nearly stepwise way, under implicit solvent conditions, with transition states that display significant aromatic features. We show Alder-Ene and direct hydride transfer pathways as two extremes of a continuous mechanistic spectrum for this kind of reactions, with the analyzed systems located approximately equidistant from both ends.