New Catalytic Methodologies for the Synthesis of Organofluorine Compounds

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Fluorine incorporation into organic compounds poses minimal steric constraints, but its strong electron-withdrawing ability can cause a modulation of the pKa of neighbouring functional groups or the energy of frontier orbitals. Fluorine can also strengthen or participate in key intra- and intermolecular electrostatic interactions. As a result of the effects caused by fluorine incorporation, it has become key to the design of drugs, agrochemical agents, and advanced materials among other areas. This is remarkable as fluorine is virtually absent from naturally occurring organic compounds, and there is now a growing need for robust methods to access and build complexity into organofluorine compounds. Furthermore, sustainable syntheses are highly desirable and may come from improved reaction conditions minimizing chemical wastes, and from novel disconnections enabling short syntheses. Transition-metal catalysis may be a key tool to engage organic compounds into new reactivity patterns, streamlining the synthesis of fluorinated molecules via reliable and step-efficient processes. Thus, the overarching goals of this research program will be (1) to manipulate C-H and C-C bonds to better access and derivatize organofluorine compounds; (2) to establish processes for preparing strained or fused, fluorinated cyclic compounds, and investigate their novel applications towards new fluorinated motifs; and (3) to explore the bioisosterism of new fluorinated motifs and their potential as molecular probes. Over the next five years, under this Discovery Grant, graduate and undergraduate students involved in my research activities will develop new synthetic routes to fluorinated molecules by exploiting C-H and C-C bonds as handles for functionalization, and will expand on the reactivity, installation, and applications of strained fluorinated carbocycles, particularly bicyclo[1.1.1]pentanyl derivatives and gem-difluorocyclopropanes. The overall research program will result in major advances that will influence how we construct and manipulate organofluorine compound, benefiting academia, the Canadian industry (e.g. pharmaceutical, agrochemical), and efforts in R&D at large.