Copper-Mediated Synthesis of (E)-β-Aminoacrylonitriles from 1,2,3-Triazine and Secondary Amines

We describe a simple protocol for the synthesis of (E)-beta-aminoacrylonitriles via Cu(OAc)(2)-mediated nucleophilic addition of secondary amines to 1,2,3-triazine 1 and an aerobic oxidation reaction. The reactions, which were studied with a broad substrate scope, are effective with cyclic, heterocyclic, aliphatic, allylic, and benzylic amines as well as L-proline derivatives. The reactions use catalytic Cu(OAc), to promote 1,2,3-triazine addition with various secondary amines, followed by in situ loss of nitrogen and subsequent imine oxidation to generate the corresponding (E)-beta-aminoacrylonitriles in good yields with excellent stereoselectivities. These copper(II)-mediated aerobic oxidation reactions proceed under mild reaction conditions by oxidation of the Cu(II) species using molecular oxygen to complete the cycle without the participation of ligand, base or chemical oxidant additives.

Automated summary

In this paper, a simple protocol for the synthesis of (E)-β-aminoacrylonitriles via Cu(OAc)(2)-mediated nucleophilic addition and oxidation reactions is described. The method shows high effectiveness and stereoselectivity with various substrates. The reactions proceed under mild conditions without the need for additional additives.