Organocatalytic Synthesis of Methylene-Bridged N-Heterobiaryls

摘要

A one-step synthesis of 1,1′- and 2,2′-methylene-bridged N-heterobiaryls directly from the corresponding N-heterocycles in a reaction with methylmagnesium chloride in the presence of catalytic amounts of N,N,N′N′-tetramethylethylenediamine (TMEDA) under thermal and microwave conditions is reported. The split-and-merge methylenation of 2,2′-N-heterobiaryls and the direct ortho-alkylation of quinoline and isoquinoline with Grignard reagents have also been developed. Mechanistic studies identified several intermediates and provided insights into the formation and roles of magnesium hydride species in the process.