Aza Diels-Alder Reactions of Nitriles, N,N-Dimethylhydrazones, and Oximino Ethers. Application in Formal [2+2+2] Cycloadditions for the Synthesis of Pyridines

作者:Hamzik Philip J.; Goutierre Anne-Sophie; Sakai Takeo; Danheiser Rick L.*
来源:Journal of Organic Chemistry, 2017, 82(24): 12975-12991.
DOI:10.1021/acs.joc.7b02503

摘要

Metal-free, formal [2 + 2 + 2] cycloaddition strategies for the synthesis of polycydic pyridine derivatives are described. The overall transformation proceeds via a two-stage pericyclic cascade mechanism. In the first step, an intramolecular propargylic ene reaction generates a vinylallene that is necessarily locked in the s-cis conformation. This vinylallene exhibits exceptional reactivity as a Diels-Alder reaction partner and engages in [4 + 2] cycloadditions with normally unreactive azadienophiles including unactivated cyano groups and heterosubstituted imine derivatives such as dimethylhydrazones and oximino ethers. Few examples of oximino ether Diels-Alder reactions have been reported previously, and normal electron-demand [4 + 2] cycloadditions of unactivated dialkylhydrazones are unprecedented. Overall, this metal-free formal [2 + 2 + 2] cycloaddition provides access to polycydic pyridine derivatives and complements transition-metal-catalyzed [2 + 2 + 2] strategies.

  • 出版日期2017-12-15
  • 单位MIT