The Chemical Synthesis Program of the NSF Chemistry Division supports the research of Professor Martin Burke in the Department of Chemistry at The University of Illinois at Urbana-Champaign. Professor Burke and his students are developing new methods for assembling molecular building blocks that contain non-planar "sp3" carbon atoms. Such methods have the potential to enable a simple, building block-based approach for making many different types of molecules with well-defined three-dimensional shapes. Such molecules have many potential applications, including serving as medicines, biological probes, diagnostics, agrochemicals, materials, molecular technologies, perfumes, sweeteners, and many other household products. One goal of the research is to develop new ligands for palladium that promote such assembly reactions in a manner that allows the three-dimensional shapes of the building blocks to be translated into the shapes of the final products. The project also aims to incorporate these new coupling methods and a readily accessible collection of building blocks into a fully automated platform for on-demand small molecule synthesis of a large family of biologically active molecules found in nature. This research is well suited for the education of scientists at all levels. Professor Burke's group is also well positioned to provide the highest level of education and training for students from groups that are underrepresented in science.
The development of new methods for site- and stereospecific cross-coupling of stereogenic sp3 carbon atoms largely comprise an actionable roadmap toward automated building block-based construction of many different types of small molecules. The proposed studies aim to develop such methods for coupling unactivated chiral secondary non-racemic boronic acids that possess one or more stereogenic sp3-hybridized carbon atoms. New phosphine ligands are targeted that promote such couplings by favoring transmetalation and reductive elimination at sp3-hybridized carbons while eliminating or minimizing undesired beta-hydride elimination reactions. These methods are evaluated for their capacity to enable fully automated total synthesis of an entire family of complex natural products from pre-assembled chiral building blocks. This research yields new strategies and methods that enable both the manual and automated synthesis of many different types of chiral Csp3-rich small molecules. This research program also contributes to the training of graduate and undergraduate students at the frontiers of organic synthesis.
