This project is focused on the exploration of a [4+3]-cycloaddition/quasi-Favorskii process. This reaction sequence, which provides rapid access to highly complex structures, will be applied to the synthesis of three natural products: the prostanoid tricycloclavulone, the alkaloid magellaninone and the antitubercular agent elisapterosin B. Each natural product will allow the development of the [4+3]-cycloaddition of a unique cyclic allylic cation, from cyclopentenyl to cycloheptenyl. Two different protocols for generating the allylic cations will be studied. The quasi-Favorskii rearrangement of the cycloadducts will be an integral part of the total synthesis efforts. This reaction will afford compounds that could in principle be obtained directly through the Diels-Alder cycloaddition of dienes with cycloalkenyl carboxaldehydes. Stereochemical differences between the cycloaddition processes suggest that the [4+3]-cycloaddition will be more suited for the total syntheses of the targets. The complementary cycloaddition processes will be compared both computationally and experimentally in the context of cycloadditions with cyclopentadiene and other cyclic dienes. Intermolecular and intramolecular [4+3]-cycloaddition/quasi-Favorskii processes of noncyclic dienes will also be explored.
With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Michael Harmata, of the Department of Chemistry at the University of Missouri at Columbia. Professor Harmata and his students are developing an unusual and efficient route for the rapid construction of complex organic molecular structures. The methodology under exploration, combining a ring-forming "cycloaddition" reaction with a subsequent molecular rearrangement reaction, will be applied to the synthesis of several naturally occurring molecules in order to establish its versatility and generality. The general idea is to take advantage of unique processes combined with simple starting materials to increase molecular complexity quickly. Complex organic structures often play critical roles in the development of new drugs or new materials that will be increasingly important as technological developments in molecular medicine and nanotechnology increase.
