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Intramolecular Diels−Alder Reaction of N-Alkyl-2-cyano-1-azadienes:  A Study of the Eschenmoser Cycloreversion of Dihydrooxazines as a Route to N-Alkyl-2-cyano-1-azadienes

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journal contribution
posted on 04.04.1997, 00:00 by Irina A. Motorina, Frank W. Fowler, David S. Grierson
In connection with the development of the intramolecular Diels−Alder reaction (IMDA) of 1-azadienes, the 5,6-dihydro-4H-1,2-oxazine 12 has been evaluated as a synthon equivalent of the 2-cyano-1-azadiene system. It was found that the dihydrooxazonium salt 27, generated in situ from the cyclic hydroxamic acid derivative 26, is converted directly to azadiene 4a via tautomerization to the corresponding enamine and a particularly facile Eschenmoser type cycloreversion process. Conditions were subsequently found for the preparation of synthon 12. N-Alkylation of this intermediate with alkyl bromides in the presence of Ag+ ion also resulted in direct formation of the 2-cyano-1-azadiene products 38ad and 4a. Microwave irradiation of a benzene solution of azadiene 4a proved to be a convenient means to effect its IMDA conversion to indolizidine 5a. To avoid decomposition of azadiene 38c, its intramolecular cycloaddition giving 40 (60%) was achieved by flash vacuum thermolysis.