This research award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports work by Professor John F. Hartwig at the University of Illinois at Urbana-Champaign to develop reactions at typically unreactive C-H bonds. This work will create new methods to prepare organic molecules by selective chemical transformations at positions that are inert to most reagents. Complexes containing bonds between transition metals and boron catalyze these reactions, and this grant will reveal the properties of the transition metal that lead to this unusual reactivity. The reactions catalyzed by these complexes have been and will continue to be applied to the synthesis of polymers containing new properties, organic molecules with enhanced abilities to emit light, components of catalysts for other reactions, and organic probes for understanding biological systems. Work emanating from the proposed research is part of new curricula for the classroom, short-courses, many external lectures, and a major textbook project that will be completed in the next grant period by the PI.
This research will lead to new methods to conduct chemical synthesis in fewer steps, with less waste, and with less reliance on the installation and protection of functional groups. In addition, this research creates the underlying principles on which future design of catalysts and processes for more efficient synthesis are based. Studies to define how the electronic properties of the metal and how electrophilic or nucleophilic properties of the reactive ligand affect C-H bond cleavage and functionalization will create these principles.
Organic synthesis has typically been based on certain collections of atoms that are reactive. Carbon-hydrogen bonds are the portions of molecules that are typically the least reactive, but are the most common bond in organic compounds. Thus, the invention of reactions that occur at carbon-hydrogen bonds provide opportunities to stitch together organic molecules. Reactions that occur at one carbon-hydrogen bond over another – rather than at a random assortment of carbon-hydrogen bonds – are the most challenging to develop, but are revolutionizing organic synthesis. This area of research focuses on a reaction we discovered, what has become one of the most widely adopted reactions that occurs at a C-H bond. We have identified the most active catalyst known for this reaction, have shown that this new catalyst converts the least reactive alkyl C-H bonds to carbon-boron bonds and have identified a catalyst for similar formations of carbon-silicon bonds. In addition, we have shown new reactions that the products of these C-H bond functionalizations undergo. These reactions include reactions that form carbon-carbon bonds in new ways. These reactions, along with the conversions of C-H to C-B bonds lead to new transformations of organic compounds important for the synthesis of organic molecules with function in human health, agro-science, and material science. In addition to the invention of these new reactions, we have conducted studies to dissect the factors that lead to high catalyst activity. We have shown that the metal must have a high degree of electron density and should have an uncrowded active site. This information was unknown before we began our studies because the C-H bond in these reactions is cleaved by a new class of chemical reaction.
