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

• Published in: ACS catalysis Vol. 12; no. 21; pp. 13792 - 13804
• Main Authors: Takimoto, Masanori, Liu, Mingyu, Nishiura, Masayoshi, Hou, Zhaomin
• Format: Journal Article
• Language: English
• Published: American Chemical Society 04.11.2022
• Subjects: organoaluminums; cross-coupling reaction; pyridines; C−H activation; rare-earth metal catalysts
• ISSN: 2155-5435; 2155-5435
• DOI: 10.1021/acscatal.2c04396

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 α-mono-allylated, α-mono-benzylated, and α-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.