Synthesis of Substituted Pyridines from Cascade [1 + 5] Cycloaddition of Isonitriles to <i>N</i>-Formylmethyl-Substituted Enamides, Aerobic Oxidative Aromatization, and Acyl Transfer Reaction
作者:Chuan-Hu Lei、De-Xian Wang、Liang Zhao、Jieping Zhu、Mei-Xiang Wang
DOI:10.1021/ja401701x
日期:2013.3.27
A novel strategy for de novo synthesis of pyridines featuring an unprecedented a-addition of aldehyde and enamide to isonitrile as a key step is described. Under mild conditions, a cascade reaction involving Zn(OTf)(2)-promoted [1 + 5] cycloaddition of isonitrile with N-formylmethyl-substituted enamide, facile aerobic oxidative aromatization and intermolecular acyl transfer from the pyridinium nitrogen to the 5-hydroxy oxygen, and finally acylation of the 4-amino group by an external acyl chloride efficiently afforded 2-substituted 4-acylamino-5-acyloxypyridines in good to excellent yields.