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

Abstract

Metal-free, formal [2 + 2 + 2] cycloaddition st rategies for the synthesis of polycyclic 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 vinyl-allene 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 aza dienophiles 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 polycyclic pyridine derivatives and complements transition metal-catalyzed [2 + 2 + 2] strategies.