This proposal details the development of new synthetic methodology based upon trapping of photochemically generated oxyallyl zwitterions by pendant nucleophiles or 1,3-dienes. Preliminary results indicated potential generality in the internal nucleophilic trapping reaction using either carbon or heteroatom nucleophiles. Concerted [4+3]-cycloadditions have also been demonstrated both inter- and intramolecularly. Although initial results have been positive, the scope and limitations of these reactions are unknown this point. It is proposed that trapping by carbon nucleophiles and pendant dienes be systematically amined. Potential application of this methodology to the avermectins and cardenolides is presented. In addition the bicyclic trapping products appear to be amenable to Grob-type fragmentation, providing access medium-ring products. Application of such a protocol to eight-membered cyclic ethers and the cyclooctanoid sesquiterpene precapnelladiene is discussed. An important issue which will be addressed is asymmetric induction during zwitterion formation. Several approaches to probe the viability of asymmetric 4-pyrone photochemistry have been proposed. The ability to obtain adducts in optically pure form is of great importance as regards the biomedical implications of the proposed research. Many of the reactions to be investigated can theoretically provide very efficient cess to advanced intermediates related to clinically useful drugs. The long-term goal of this research is to develop this new methodology to such a point that synthetic approaches to biologically active natural products can be attempted.
