A THEORETICAL-STUDY OF THE DITHIONITE REDUCTION OF PYRIDINIUM SALTS

The dithionite reduction of pyridinium salts results in the preferential formation of the 1 A-dihydropyridines over the other possible (1,2 and 1,6) structural isomers. Theoretical studies performed in the framework of the AM1 molecular orbital approximation both on some simple, model molecules (dihydrol-methyl-3-nicotinamide, 1, and dihydro-1-methyl-3-methyl-nicotinate, 2) and more complex derivatives (1 -methyl-dihydro-pyridine-3-carboxylates of estradiol, 3, and azidothymidine, 4) supported thermodynamic product control. The increased relative thermodynamic stability of the 1,4-dihydropyridine isomers is explained by favorable electronic interactions (homoaromaticity, hyperconjugation) governing in these derivatives. The calculated data support existing experimental evidence for product formation and isomer stability. (C) 1993 John Wiley & Sons, Inc.