In this project funded by the Chemical Synthesis Program of the Chemistry Division of the National Science Foundation, Professor Valery V. Fokin of the Department of Chemistry at The Scripps Research Institute will develop a mechanistically driven approach to catalytic reaction optimization that takes advantage of real-time monitoring of reactions without putting them into constraints of model systems. Reactions to be probed involve 2+3 cycloadditions to alkynes to form a variety of five-membered heterocycles which undergo further reactions to form a number of reactive intermediates, including metal carbene complexes. This research focuses on the critical role of transient catalyst behaviors and, in the context of the proposed work, on the defining role of weak, rapid, and reversible interactions of alkynes with transition metal catalysts.
A successful outcome to this research will result in practical synthetic methods that will allow chemists, biologists, and materials scientists to reliably assemble a variety of complex molecules with defined geometry from readily available starting materials under experimentally simple conditions. Practical synthesis of such molecules will have an impact on new and inexpensive pharmaceuticals, new materials, and advanced agrochemicals. Additionally, the next generation of scientists in catalytic synthetic chemistry will be trained in state-of-the-art techniques.