Various quinone methides, which are proposed to be key intermediates in the formation of naturally occurring products, will be prepared and studied. The objectives of this study will be to: (1) obtain a structure-activity relationship for the fate of quinone methides, (2) to generate quinone methides by laser flash photolysis and study their properties directly, and (3) to trap quinone methides as cyclopropyl derivatives. Structure-activity relationships involving the reactions of electrophiles and nucleophiles with quinone methide derivatives of naphthalene, anthracene, isoquinoline, and indole will be pursued. These derivatives are chosen because of their similarity to natural products. The laser flash generation of quinone methides will allow UV-visible spectral studies of these intermediates, quinone methide pKa determinations, and kinetic studies of the fate of the quinone methide. To provide further evidence for quinone methide intermediates, benzimidazole derivatives will be formed where the intermediate quinone methide will be trapped as a spirocyclopropane derivative. %%% This grant from the Organic Dynamics Program supports the work of Professor Edward Skibo at Arizona State University. Quinone methides are reactive intermediates that have been proposed to be key intermediates in the synthesis of naturally occurring molecules that are found in plants. Since quinone methides are very reactive, they are normally produced in very low concentration and cannot be detected directly by spectroscopic methods. In this research, these intermediates will be generated by an intense light source to give high concentrations of the quinone methides so that they can be detected by spectroscopic measurements. The presence of these intermediates will also be detected indirectly by trapping reactions to give a product that is indicative of these intermediates. In addition, a relationship between the structure of quinone methides and their reactivity with other species will be determined. These studies will make it possible to understand the origin of a large class of natural products and to develop new methods for the reductive cleavage of DNA.
