Synthesis and Reactions of Haloazodienes. A New and General Synthesis of Substituted Pyridazines

• Published in: Journal of organic chemistry Vol. 61; no. 25; pp. 8921 - 8934
• Main Authors: South, Michael S, Jakuboski, Terri L, Westmeyer, Mark D, Dukesherer, Daniel R
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 13-12-1996
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo960029e

The reaction of dihalohydrazones with Hünig's base gives 1-carbethoxy-3-phenyl-4-haloazodienes in - situ, which were found to combine with a variety of electron rich olefins to yield halo-substituted tetrahydropyridazines (Scheme and Table ). These haloazodiene cyclizations are best characterized as inverse electron demand, 4 + 2 hetero Diels−Alder reactions that maintain a high degree of regio- and stereochemical control (Schemes and ). The chloro-substituted tetrahydropyridazines that are formed give high yields of substituted pyridazines upon treatment with base (Table ). The sequence of a chloroazodiene cyclization to a tetrahydropyridazine followed by an aromatization constitutes a new and general synthesis of substituted pyridazines. In contrast to the haloazodiene cyclizations, the novel cyclization reactions of the in - situ generated 1-carbethoxy-3-phenyl-4,4-dichloroazodiene were found to give N-aminopyrroles and pyridazines when combined with acyclic enamines (Table ). However, reactions with cyclic enamines gave the N-aminopyrroles, pyridazines, a dihydropyridazine as products as well as the noncyclized enamine intermediates (Table ). The noncyclized enamines could be converted to the N-aminopyrroles simply upon heating to higher temperatures, indicating a stepwise mechanism (Schemes and 9). The examples described here are the first reported cyclization reactions for dichloroazodienes.