New Cycloaddition and Annulation Strategies for Organic Synthesis

In this project, Professor Danheiser will develop new methods for the efficient synthesis of cyclic organic molecules. The goal of this research program is the development of new strategies with the power to dramatically streamline the synthesis of carbocyclic and heterocyclic organic compounds. Pericyclic reactions serve as the primary vehicle to be exploited in this research, with most efforts focused on the design of convergent benzannulation strategies based on cascades of pericyclic reactions. In the proposed research, the development of a "tandem strategy" will be investigated in which a vinylketene based benzannulation reaction is employed in conjunction with various heterocyclization processes to provide efficient access to highly substituted polycyclic benzo-fused heterocyclic systems including indoles and carbazoles. The application of this chemistry to the synthesis of the antioxidant alkaloid antiostatin A1, the antifungal antibiotic carbazomycin A, the marine alkaloid herbindole C, the redox cofactor pyrroloquinoline quinone (PQQ), and an electronically interesting pentacyclic heteroaromatic system will be investigated.

Carbocyclic and heterocyclic ring systems are incorporated in the structures of numerous biologically important compounds, and the development of highly efficient methods for their synthesis has great value in providing improved access to molecules with important applications in medicine, materials chemistry, and many other areas. Synthesis is often described as the "enabling technology" of chemistry. The synthetic methods developed in the proposed research will provide researchers in both academia and industry with new tools for the synthesis of important heterocyclic compounds with applications in medicine, agriculture, electronics, and other areas. The graduate students supported under this program will receive training to develop their skills as synthetic chemists, and will also receive training in scientific ethics and training to develop their oral and written communication skills. The graduate students will also serve as coordinators for the MIT Outreach Program which each year visits ca. 25 high schools in the New England region providing presentations on chemistry and careers in science. Approximately 1200 high school students attend these presentations each year, with ca. 35% of the students being members of underrepresented minority groups.