Novel reductive amination of nitriles: An efficient route to 5-hydroxypiperidone-derived N,N-acetals

5-Hydroxypiperidin-2-one is a versatile building block for the preparation of potentially biologically active compounds. We detail an enantioselective biocatalytic approach towards its synthesis using (S)-hydroxynitrile lyase (HNL)-mediated cyanohydrin formation, followed by hydrogenation. By adjusting the conditions of the latter step, we were able to obtain 5-hydroxypiperidinone-derived (bicyclic) N,N-acetals via an unprecedented reductive amination of the nitrile group, as well as form N-alkylated 5-hydroxypiperidinone in a single step from the same cyanohydrin intermediate.