Regioselective Benzylic C-H Alumination and Further Functionalization of 2-Alkylpyridines by Yttrium Catalyst

The regioselective benzylic C-H alumination of various symmetrical and nonsymmetrical 2,6-alkylpyridines catalyzed by a half-sandwich yttrium complex has been developed. The resulting alkylaluminum species bearing a pyridyl ring moiety can be transformed to the corresponding alcohols by oxidation. Moreover, the Cu-catalyzed allylation and benzylation and Pd-catalyzed arylation reactions can be applied to the resulting alkylaluminum species, giving the corresponding alpha-mono-allylated, alpha-mono-benzylated, and alpha-mono-arylated 2-alkylpyridine derivatives, respectively, in good to high yields. Unsymmetrically substituted 2,6-dialkylpyridines can be synthesized from simple symmetrical substrates by repeating such C-H alumination/C-C bond formation processes. Because of the high regioselectivity of the present C-H alumination and the subsequent C-C bond formation, this protocol may serve as a desirable method for the synthesis of nonsymmetrically-2,6-disubstituted pyridine derivatives.

Automated summary

A regioselective benzylic C-H alumination method has been developed for various symmetrical and nonsymmetrical 2,6-alkylpyridines. The resulting alkylaluminum species can be transformed to the corresponding alcohols by oxidation. Additionally, Cu-catalyzed allylation and benzylation reactions, as well as Pd-catalyzed arylation reactions, can be applied to the alkylaluminum species to obtain α-mono-allylated, α-mono-benzylated, and α-mono-arylated 2-alkylpyridine derivatives.