Influence of a hydroalcoholic solvent on the enantioselectivity of α-amino nitrile hydration catalysed by chiral ketones

Abstract

The enantioselective hydration of α-aminonitriles 1, RCH(CN)NH₂[1a: R = PhCH₂; 1b: R = Prⁱ; 1c: R = Ph] has been achieved in an alkaline hydroalcoholic medium in the presence of chiral ketonic catalysts. Of the different ketones used, (-)-(5R,3R,2R)-5-(methylethenyl)-3-cyano-2-methylcyclohexanone (8) gives rise to significant enantioselectivity [e.g. for the substrate 1c, k_D/k_L= 2.1; T= 10 °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 Dα-aminonitrile as shown for the hydration of 1c for which the ratio k_D/K_L increases threefold when the percentage of propan-2-ol increases from 10 to 95%.