Site-Selective C–H Alkenylation of N-Heteroarenes by Ligand-Directed Co/Al and Co/Mg Cooperative Catalysis

We report herein the design and development of cobalt/aluminum- and cobalt/magnesium bimetallic catalysts, supported by a phosphine/secondary phosphine oxide (PSPO) bifunctional ligand, for the site-selective C–H alkenylation of nitrogen-containing heteroaromatic compounds with alkynes. These catalysts enable the alkenylation of pyridine, pyridone, and imidazo[1,2-a]pyridine derivatives at the C–H site proximal to the Lewis basic nitrogen or oxygen atom, which represents a selectivity profile distinct from that of the previously developed cobalt–diphosphine/aluminum Lewis acid catalyst. The alkenylated products were obtained in moderate to good yields with syn-selectivity across various heterocycles as well as differently substituted internal alkynes. Kinetic isotope effect experiments on the pyridine C–H alkenylation suggest that the C–H activation occurs in an irreversible manner, while its relevance to the rate-limiting step depends on the reaction conditions. Density functional theory calculations indicate that ligand-to-ligand hydrogen transfer is the mechanism that operates commonly across the substrates used in the present study.