C-4 Regioselective Alkylation of Pyridines Driven by Mechanochemically Activated Magnesium Metal.

Mechanochemically activated magnesium(0) metal as a highly active mediator driving direct C-4-H alkylation of pyridines with alkyl halides has been developed. Excellent regioselectivity and substrate scope, including those containing reducible functionalities, free amines, and alcohols, as well as biologically relevant molecules were achieved to access 4-alkylpyridine products. Preliminary mechanistic studies suggested a radical-radical coupling pathway.