Synthesis and Reactions of Haloazodienes. A New and General Synthesis of Substituted Pyridazines.
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 2 and Table 1 ). 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 5 and 6). The chloro-substituted tetrahydropyridazines that are formed give high yields of substituted pyridazines upon treatment with base (Table 1). 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 3 ). However, reactions with cyclic enamines gave the N-aminopyrroles, pyridazines, a dihydropyridazine as products as well as the noncyclized enamine intermediates (Table 4 ). The noncyclized enamines could be converted to the N-aminopyrroles simply upon heating to higher temperatures, indicating a stepwise mechanism (Schemes 8 and 9). The examples described here are the first reported cyclization reactions for dichloroazodienes.
South
Michael S.
MS
Ceregen Division of Monsanto Corporation, 800 North Lindbergh Boulevard, St. Louis, Missouri 63167.
Jakuboski
Terri L.
TL
Westmeyer
Mark D.
MD
Dukesherer
Daniel R.
DR