Novel Reductive Amination of Nitriles: An Efficient Route to 5‐Hydroxypiperidone‐Derived <i>N</i>,<i>N</i>‐Acetals

Abstract

Abstract 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.