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.