Mechanism-Guided Development of Fluorination Chemistries: Funded by NSF award (2453934) 2025-2028
We are exploring the use of silver(II) fluoride in acetonitrile as a uniquely powerful reagent to carry out a diverse number of transformations including C-H fluorination of sp2 and sp3 C–H bonds, difluorination of olefins and aromatic heterocycles, and site-specific substitution of readily available starting materials like carboxylic acids and alkyl halides into the corresponding fluorides. We propose to elucidate the mechanistic details of these newly discovered reactions in order to provide the foundation for the expansion of this chemistry to an even broader range of reaction manifolds.
Mechanistic Studies of palladium-catalyzed C-H activation : Funded by NIH MIRA Award (R35 GM145320) 2022-2027
Selective activation of inert C-H bonds by Pd is a burgeoning area of research where new reaction discovery has significantly outpaced mechanistic understanding. Mechanistic studies in this area of catalysis have largely focused on determination of kH/kD and computational studies. The kH/kD experiment informs if the C-H activation step is the rate-determining step but provides no information regarding the subsequent C-H functionalization. In this proposal, we illustrate the use of 13C KIEs and DFT calculations to be a simpler, yet more quantitative alternative to kH/kD experiments for the elucidation of the transition state geometry of multiple steps in the overall reaction mechanism.
Mechanistic Studies of nickel metallaphotoredox catalysis : Funded by NIH MIRA Award (R35 GM145320) 2022-2027
Over the past decade, the merger of photoredox and Ni catalysis has enabled a staggering range of novel transformations under relatively mild conditions. Fundamental mechanistic questions such as the oxidation state at the Ni center (Ni0 or NiI) during key mechanistic steps remain unresolved. Computational studies have attempted to bridge this gap but the possibility of low-spin and high-spin states for intermediates and TSs makes these studies particularly challenging and difficult to validate experimentally. We have established that 13C KIEs supported by DFT calculations are sensitive experimental probes of the oxidation state, coordination number, and spin state at the metal center during the TS for key mechanistic steps in the catalytic cycle for TM catalyzed reactions. We propose to investigate a broad range of C-C and C-X (X=N,O) bond-forming methodologies in this growing area of contemporary catalysis to gain unprecedented insights into the intricate details of these complex reaction mechanisms.
Timeline and overview of active research projects in the Vetticatt Lab (2013-present)
