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

Article abstract of DOI:10.1016/j.tet.2004.08.079

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. Graphical Abstract.