In this project funded by the Chemical Catalysis Program of the Chemistry Division, Professor Jack Norton of Columbia University examines radicals as versatile intermediates for the construction of complex chemical molecules. While the bond-forming reactions of radicals are predictable, and their tolerance of functional groups is high, their use in sustainable synthesis remains largely untapped. This research is done in an interdisciplinary manner, combining new synthetic methods with research in quantum chemistry, mechanistic inorganic chemistry, and biological chemistry. The first-row transition metals (vanadium, titanium, cobalt and chromium) investigated in this research are ideally suited for sustainable catalysis. They are nontoxic (in the oxidation states to be used) and replace complexes using rare and expensive metals. The use of dihydrogen (H2) as the terminal reductant resolves longstanding environmental and toxicity issues associated with reductive radical reactions. New catalysts are being synthesized and quantum chemical methods are being used for virtual catalyst screening and mechanistic determinations. Sustainable methods for catalyzing the hydrogen-mediated reduction of epoxides to alcohols, reductive radical cyclizations with H2, and radical cycloisomerizations by various dienes, enynes and epoxyenes are under investigation. These methods are applied to the efficient, general, and stereoselective syntheses of functionalized eight- and nine-membered ring lactams and cyclic amines, and to the syntheses of polycyclic Aspidosperma and Kopsia indole alkaloids such as voafinidine and grandilodine A.
This project is performed in collaboration with Professors Stefan Grimme and Andreas Gansaeuer of the Rheinische Friedrich-Wilhelms-Universitaet in Bonn, Germany and Professor Chaozhong Li of the Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, in China. Together, these groups combine their separate areas of expertise in the preparation and study of catalytic radical reactivity and mechanisms. In additional to the technical applications of this research by the chemical industry, the broader impacts of this work include the training of graduate students and an international exchange of ideas and expertise.
