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

Abstract

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 1b– g is highly ( R)-selective, whereas the methyl compound 1a reacts ( S)-selectively. With MeHNL from cassava, all 2-alkyl derivatives 1 react ( S)-selectively. The catalytic activity of both PaHNL and MeHNL decreases with increasing size of the substituent in substrates 1 . The diastereoselectivity of HCN additions to 2-alkoxy cyclohexanones 4 and 3-substituted cyclohexanones 6 , however, is only moderate. The absolute configuration of the synthesized cyanohydrins was determined by X-ray crystallography of O- p-bromobenzoyl derivatives.