Hydroxynitrile lyase-catalyzed addition of HCN to 2- and 3-substituted cyclohexanones

The addition of HCN to monosubstituted cyclohexanones yielding cyanohydrins is strongly catalyzed by hydroxynitrile lyases (HNLs). With PaHNL from bitter almonds, the addition to 2-alkyl cyclohexanones is highly (R)-selective, whereas the methyl compound reacts (S)-selectively. With MeHNL from cassava, all 2-alkyl derivatives react (S)-selectively. The catalytic activity of both PaHNL and MeHNL decreases with increasing size of the substituent in substrates . The diastereoselectivity of HCN additions to 2-alkoxy cyclohexanones and 3-substituted cyclohexanones , however, is only moderate. The absolute configuration of the synthesized cyanohydrins was determined by X-ray crystallography of O-p-bromobenzoyl derivatives.