In our proposed research we will aim to extend the applicability of singlet oxygen reactions in organic synthesis by photooxidation studies on functional units which react efficiently and specifically with this highly electrophilic excited species. Singlet oxygen is a remarkable oxidizing gent which is readily available, inexpensive and specific in its action. Its applications in synthesis have yet to be fully exploited by organic chemists. In our further work, we hope to extend the scope and versatility of these reactions in the formation of products of medicinal interest. Specifically, we will continue our studies on the singlet oxygen- promoted conversion of oxazoles to triamides as a route to medium-size as well as macrocyclic lactones and lactams. In particular, the reaction sequence involving nucleophilic substitution on the oxazole ring, followed by photooxidation to generate an activated carboxylate, effectively employs the oxazole template as a carbonyl-1,1-dipole (+C=O) equivalent. Using the singlet oxygen-enamine cleavage reaction to generate vicinal tricarbony derivates, we will explore new ways of introducing this highly electrophilic unit into organic systems by appending acceptor sites such as vinyl, acetylenic and cyclopropyl residues to the tricarbony aggregate. In one application, this procedure will provide new routes to intermediates in the indole alkoloid field. The reactions of singlet oxygen with hydroxypyrroles and other pyrrole derivatives will be investigated as a practical means of introducing oxygenated functionality at specific sites in organic molecules. Applications in the synthesis of intermediates related to mytomycin, swainsonine, castanospermine and the pyrrolizidine alkaloids will be examined. Pyrrole photooxidation will also be studied as a synthetic (and possible biomimetric) route to naturally-occurring plant products.
