Chiral NADH models in the pyrido[3,2-c]azepin series. Conformational effect of the carbonyl group in the stereocontrol of reductions

Asymmetric reduction of methyl benzoylformate with the chiral NADH model 2 in the pyrido[3,2-c]azepin series afforded methyl mandelate in 91% optical yield. The high enantioselectivity observed with model 2 is compared with cyclized analogues 1a and 1b in the naphthyridine and pyrrolo[3,4-b]pyridine series respectively. The stereochimical outcome of the reaction is discussed in relation to the out-of-plane orientation of the amide group with respect to the dihydropyridine ring in the transition state.