INFLUENCE OF A HYDROALCOHOLIC SOLVENT ON THE ENANTIOSELECTIVITY OF ALPHA-AMINO NITRILE HYDRATION CATALYZED BY CHIRAL KETONES

The enantioselective hydration of alpha-aminonitriles 1, RCH(CN)NH2 [1a: R = PhCH2; 1b: R = Pr(i); 1c: R = Ph] has been achieved in an alkaline hydroalcoholic medium in the presence of chiral ketonic catalysts. Of the different ketones used, (-)-(BR,3R,2R)-5-(methylethenyl)-3-cyano-2-methylcyclohexanone (8) gives rise to significant enantioselectivity [eg. for the substrate lc, k(D)/k(L) = 2.1; T 10-degrees-C; solvent, water-propan-2-ol (45:55,v/v)]. Although the structure of the catalyst could probably be improved, we show in this paper that the efficiency and especially the enantioselectivity of the catalyst are not only under steric control but also depend on the nature and composition of the hydroalcoholic solvent. Thus, for the three aminonitriles studied in the presence of the catalyst 8, the increase in percentage of propan-2-ol favours the hydration of the D alpha-aminonitrile as shown for the hydration of lc for which the ratio k(D)/k(L) increases threefold when the percentage of propan-2-ol increases from 10 to 95%.