Selective Para-Vinylation of Cyano-Pyrazine.

A metal-free selective para-vinylation of cyano-pyrazines with ketones is reported. This reaction proceeds via nucleophilic addition-elimination under mild conditions, using LiHMDS as a base and THF as a solvent at 80 °C for 12 h. A broad substrate scope is demonstrated with 28 examples, affording stable enol products in yields of up to 93%. The enol configuration of the product is confirmed by IR spectroscopy and X-ray single-crystal diffraction. Control experiments indicate no radical involvement and highlight the necessity of methyl ketones. This methodology provides an efficient approach for functionalizing cyano-pyrazines, which are precursors to pharmaceuticals like pyrazinamide, and expands the synthetic toolbox for pyrazine-derived compounds.