Stable annelated chiral NADH models with a rigidified amide part in the quinoline series:: synthesis, reactivity and grafting on a Merrifield resin

The synthesis of new chiral nicotinamide adenine dinucleotide hydrogenated models derived from quinoline is described. Using a biomimetic approach, the out-of-plane positioning of the amide carbonyl was obtained by involving the chiral auxiliary in a lactam structure. It is shown that electron-donating groups on the benzene ring of the quinoline structure are necessary to obtain high chemical yields during the reduction of methyl benzoylformate. An interesting variation of the enantioselectivity as a function of magnesium ion concentration has been observed. Under the best conditions, methyl mandelate was obtained in up to 95% ee (R). To facilitate the recycling of these models, grafting of reagent 4 on a Merrifield resin has been developed. The resulting polymer-supported reagent 4 was tested in the asymmetric reduction of methyl benzoylformate. (C) 2001 Elsevier Science Ltd. All rights reserved.