A Facile Highly Selective Anti-Markovnikov Hydroamination of Vinyl Pyridines by Free Radical Oxidation

Graphical We report a new strategy of anti-Markovnikov hydroamination of vinyl pyridine with various amine compounds along with high selectivity. The highest yield of target product can reach 93 % in gram-scale reaction. On the basis, we proposed a kind of aza-Michael-type free radical addition mechanism, which was well supported by deuterium labeling studies and reference experiments. In this paper, we report a new and facile protocol for anti-Markovnikov hydroamination of vinyl pyridines under mild condition. In the presence of organic peroxide, pyridylethylation of a wide variety of aryl/alkyl amines with different substituent and electronic characteristics by intermolecular anti-Markovnikov hydroamination was successfully carried out. Furthermore, moderate to excellent yields were obtained along with high selectivity through condition optimization. The highest yield of target product can reach 93 % in gram-scale reaction. On the basis, we proposed a kind of aza-Michael-type free radical addition mechanism, which was well supported by deuterium labeling studies and reference experiments.