Photocatalyzed intermolecular amination for the synthesis of hydrazonamides

Hydrazonamides are fundamental building blocks in many pharmaceuticals and agricultural chemicals. Although contributions have been accomplished through multi-step reactions under harsh conditions, achieving high efficient synthetic strategy remains challenging. Considering the structural characteristic of hydrazonamides, a sequential multi-component reaction of -ketonitriles with N,N-disubstituted hydrazines is designed and developed through photocatalyzed intermeolecular amination process. This work reported here represents the first example of employ N,N-disubstituted hydrazines as two different “amine” sources, and is characterized by isotope labeling experiments. The C-CN/N-N bonds are cleaved and new C-N/C=N bonds are constructed in one-pot reaction. This protocol can be carried out without the addition of any external metals, ligands, bases, oxidants and reductants, and possesses the advantages of operational-simple, mild reaction conditions, and good functional group tolerance. Furthermore, this approach enables late-stage modifications of structural complex bioactive molecules, natural products and drugs, thus showing potential applications in the field of organo-pharmaceutical chemistry.