Regioselectivity of Hydride Transfer to and between NAD+ Analogues

Article abstract of DOI:10.1021/jo00160a023

The reaction of 1-methyl- or 1-benzylquinolinium compounds, also bearing an electron-withdrawing substituent in the 3-position, with NaBH4, gives mixtures of the corresponding 1,2-dihydroquinolines and 1,4-dihydroquinolines in which the 1,2-dihydro derivatives usually predominate.The 1,2-derivatives can be isolated.The 1,2-isomers react with the quinolinium salts, giving the 1,4-isomers and regenerating quinolinium salts.This bimolecular isomerization can be used to convert a mixture of isomers to the 1,4-isomer on a preparative scale. 3-Cyano-1,2-dihydro-1-methylquinoline also isomerizes to the 1,2-isomer in the crystalline solid.The major first product of NaBH4 reduction of 3-(aminocarbonyl)-1-benzylpyridinium ion is the 1,6-dihydro derivative.This also isomerizes to the 1,4-dihydro compound in the presence of the pyridinium ion.Reduction of quinolinium derivatives with Na2S2O4 or a dihydropyridine directly produces the 1,4-isomer predominantly.Reduction of 3-(aminocarbonyl)-1-benzylpyridinium ion with Na2S2O4 in D2O gives the 1,4-dihydro derivative, but 8percent of the deuterium is in the 2-position; presumably by reversible isomerization.This deuterium redistribution may have important consequences for the interpretation of isotope effects.