SIMPLE PREPARATIONS OF C-4-TERT-BUTYLATED NADH NAD+ ANALOGS

The addition of tert-butyl Grignard reagent to the 1-benzyl-3-carbamoylpyridinium salt (1) gives a mixture of the C-4-(2), C-6-(3), and C-2-tert-butylated dihydronicotinamides (4) in which the desired 1,4-isomer predominates. Stable cristalline 1-benzyl-4-tert-butyl-1,4-dihydronicotinamide (2) can be easily isolated. Oxidation of the product with the 1-benzyl-3-cyanoquinolinium ion (6) was found to be strongly solvent-dependent. In acetonitrile, exclusive hydride transfer gives the corresponding C-4-tert-butylated pyridinium ion (5). In methanol, an interesting tert-butyl transfer from 1,4-dihydronicotinamide (2) to quinolinium (6) occurs competitively, and predominates in the presence of a catalytic amount of formic acid; the resulting C-4-tert-butylated 1,4-dihydroquinoline derivative (8) can be readily isolated.