Synthesis and reactions of haloazodienes. A new and general synthesis of substituted pyridazines

Article abstract of DOI:10.1021/jo960029e

The reaction of dihalohydrazones with Hunig'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 tetrahydropynidazines. 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. The chloro-substituted tetrahydropyridazines that are formed give high yields of substituted pyridazines upon treatment with base. 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. However, reactions with cyclic enamines gave the N-aminopyrroles, pyridazines, a dihydropyridazine as products as well as the noncyclized enamine intermediates. The noncyclized enamines could be converted to the N-aminopyrroles simply upon heating to higher temperatures, indicating a stepwise mechanism. The examples described here are the first reported cyclization reactions for dichloroazodienes.