It has been observed that N-acyl derivatives of 1-azadienes will participate in the Diels-Alder reaction and the Cope rearrangement. Because these new reactions construct a six membered ring they have considerable potential in synthetic chemistry. Additional advantages are that they both occur with a high degree of stereochemical control and produce an endocyclic enamine derivative. Since these pericyclic reactions do not require the nitrogen atom in the cyclization step they represent a complementary strategy for the preparation of nitrogen heterocycles. It is proposed to develop these methods as valuable tools in synthetic chemistry. Studies are outlined for providing rapid access to the reactive azadiene from readily available compounds. It is also planned to investigate substituents that will enhance the pericyclic reactivity of the azadienes as well as being valuable for further structural elaboration of the product. An alpha-cyano substituent appears particularly promising. Further exploration of this theme will involve the preparation on N-acyl ketenimines and a study of their pericyclic reactivity. The reactions to be developed in this proposal provide new syntheses of six membered nitrogen heterocycles. This ring system is a common structural element in a number of compounds of interest to the biomedical community. For example, the majority of the known alkaloids, as well as a significant number of totally synthetic compounds possessing biological activity, contain this ring system. It is proposed to use the pericyclic reactions of carbon nitrogen double bonds described in this proposal as key steps in new strategies for the preparation of cephalosporin antibiotics and aminosaccharides. The latter compounds have potential as biochemical tools as well as being useful for the control of carbohydrate based dysfunctions.
