Palladium-Catalyzed Direct Arylation of Alkylpyridine via Activated N-Methylpyridinium Salts
2019
Chen, Xue | Li, Wen-jing | Li, Shun | Tang, Juan | Du, Xi | Zheng, Xue-li | Yuan, Mao-lin | Fu, Hai-yan | Li, Rui-xiang | Chen, Hua
An efficient Pd-catalyzed arylation of alkylpyridine based on the pyridinium activation strategy has been developed for synthesis of mixed aryl alkylpyridines. It was found that (1) the N-methyl group in the pyridinium salts acted as a transient activator and could be automatically departed after the reaction, (2) CuBr was an indispensable additive for achieving the C₆-selective arylation, (3) the α-branched alkyl chain on the alkylpyridine greatly increased the yield of the product. Deuterium labelling experiment revealed that in the case of the α-branched alkylpyridine, the presence of CuBr completely inhibited the H/D exchange at the benzylic position and thus enabled the selective arylation at the C₆ position. This protocol demonstrates a broad substrate scope, and with respect to both the aryl iodides and the α-branched alkylpyridine, the desired mixed aryl alkylpyridines were obtained in generally good to excellent yields.
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