Mechanochemical C-H Arylation and Alkylation of Indoles Using 3 d Transition Metal and Zero-Valent Magnesium.

Although the 3 d transition-metal catalyzed C-H functionalization have been extensively employed to promote the formation of valuable carbon-carbon bonds, the persistent problems, including the use of sensitive Grignard reagents and the rigorous operations (solvent-drying, inert gas protection, metal pre-activation and RMgX addition rate control), still leave great room for further development of sustainable methodologies. Herein, we report a mechanochemical technology toward in-situ preparation of highly sensitive organomagnesium reagents, and thus building two general 3 d transition-metal catalytic platforms that enables regioselective arylation and alkylation of indoles with a wide variety of halides (including those containing post transformable functionalities and heteroaromatic rings). This mechanochemical strategy also brings unique reactivity and high step-economy in producing functionalized N-free indole products.

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.