Synthesis of Substituted Pyridines from Cascade [1 + 5] Cycloaddition of Isonitriles to N‑Formylmethyl-Substituted Enamides, Aerobic Oxidative Aromatization, and Acyl Transfer Reaction
journal contributionposted on 27.03.2013, 00:00 by Chuan-Hu Lei, De-Xian Wang, Liang Zhao, Jieping Zhu, Mei-Xiang Wang
A novel strategy for de novo synthesis of pyridines featuring an unprecedented α-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.
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Substituted Pyridinesisonitrileoxidative aromatizationcascade reactionenamidecycloadditionAerobic Oxidative AromatizationacylaminoaldehydeAcyl Transfer ReactionA novel strategySynthesiacyl transferZnCascadepyridineacylationIsonitrilehydroxypyridinium nitrogenyieldEnamideacyl chloridesynthesisCycloaddition