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

A protocol for parallel C(sp(3))-C(sp(3)) 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.

Automated summary

A protocol for parallel C(sp(3))-C(sp(3)) coupling based on a reductive amination-nitrogen deletion reaction sequence has been developed. A compound library of 25 members was prepared with 76% synthetic efficiency after preliminary validation experiments. The proposed approach provides access to a chemical space of nearly 600,000 representatives that are underrepresented in current compound databases.