Diastereofacial selectivity of α-aminonitrile formation from substituted cyclohexanones

Abstract

The formation of α-aminonitriles from substituted cyclohexanones exhibits diastereofacial selectivity resulting in unequal amounts of the two possible geometric isomers. The degree of selectivity increases with the nature of the substitution on the cyclohexyl ring indicating that this likely results from the degree to which the substitution can ‘lock’ the conformation of the cyclohexyl ring into the most stable conformation. The ratio of trans:cis isomers seen for the reaction of 4-substituted cyclohexanones with dimethylamine hydrochloride and potassium cyanide in water were 92:8 for 4-phenyl, 81:19 for 4-t-butyl, and 62:38 for 2-methyl. Varying the size of the amino group substituents did not have a dramatic effect on the selectivity that was observed.