C-C Coupling through Nitrogen Deletion: Application to Library Synthesis

A protocol for parallel C(sp³)−C(sp³) coupling of (hetero)aromatic aldehydes and (hetero)arylmethyl amines based on a reductive amination – “nitrogen deletion” reaction sequence has been developed. After preliminary validation experiments, an illustrative compound library of 25 members was prepared with 76 % synthetic efficiency. The estimated chemical space accessible by the proposed approach covers almost 600 000 representatives that are scarcely represented in current compound databases.