Hydride transfer from 1,4-dihydropyridines to pyridinium salts: Assessment of structural and energetic factors with hantzsch ester derived compounds

Hydride exchange occurs between 3,5 - di(alkoxycarbonyl) - 1,4 - dihydropyridines and their corresponding pyridinium salts. For the case of 1,2,6 - trimethyl - 3,5 - di(ethoxycarbonyl) - 1,4 - dihydropyridine in the presence of the structurally corresponding pyridinium perchlorate, hydride is transferred to the 4-position of the pyridinium salt in a reversible “blind” reaction as revealed by deuterium labeling experiments and to the 2,6-positions irreversibly to afford 1,2,6 - trimethyl - 3,5 - di(ethoxycarbonyl) - 1,2 - dihydropyridine as final product. Removal of the methyl groups at the 2,6-positions, i.e. 1 - methyl - 3,5 - di(methoxycarbonyl) - 1,4 -dihydropyridine and its structurally corresponding pyridium perchlorate, causes hydride transfer to become completely reversible. Substitution of the 4-position with Me, i.e. 1,2,4,6 - tetramethyl - 3,5 - di(methoxycarbonyl) -1,4- dihydropyridine and its corresponding pyridinium perchlorate leads to cessation of hydride transfer: the same is true for the analogous 4-phenyl (and substituted phenyl) compounds. However, these 1,4-dihydropyridines are capable of transferring hydride at reasonable temperatures to less highly substituted pyridinium salts. Activation parameters for some of these hydride transfers have been determined, mechanistic conclusions are presented, and the consequences of these observations for experiments with “model” NADH compounds are discussed.