Fluorine incorporation into medicines, modern materials, and agricultural agents has improved their structural stability and reinvented these domains. Yet the world has not fully realized fluorine's potential. One promising approach to fluorine installation involves the direct transformation of a carbon?hydrogen bond (C?H bond) into a carbon?fluorine bond in a process known as C?H functionalization. Yet C?H functionalization processes have broader potential: they include reactions to replace C?H bonds with carbon?oxygen, carbon?sulfur, carbon?chlorine or carbon?carbon bonds. In short, C?H functionalization reactions are powerful technologies to streamline access to health-relevant small molecules. Over the last decade, some of the most important advances in C?H functionalization originated from new platforms to control the site of this reaction. Still, the utility of known C?H functionalization processes remains constrained by incomplete positional control in C?H functionalization processes. In some cases, positional control can be achieved by using a directing group. The proposed research includes new directing group strategies with the capacity to substantively extend the synthetic utility C?H functionalization reactions, with tremendous potential benefit to human health.
Medical advances depend on access to small molecule drug formulation aids, biochemical probes, imaging agents, and new chemical entities. My research program invents chemical methods that deliver first-in-kind access to to small molecules with import to human health. To do so, develop technologies that enable carbon? hydrogen (C?H) bond functionalization of sites that are hitherto untargetable because they are neither kinetically accessible based on well-developed C?H functionalization methods, nor the most reactive based on bond dissociation energy.
