CAS: Developing Nickel-Catalyzed Methods to Prepare High-Value Organofluorine Molecules

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With the support of the Chemical Synthesis program in the Division of Chemistry, Professor David Vicic of Lehigh University will study ways to introduce fluorine-containing groups into organic substrates using the earth-abundant and environmentally friendly nickel metal as a catalyst. The percentage of fluorinated pharmaceuticals among the total number of registered synthetic drugs is extraordinary (43% in 2019), and 47% of all agrichemicals that were assigned new ISO common names contained fluorine from 1998-2020. As such, developing cheaper and more efficient catalytic methods to incorporate fluorinated groups is paramount to the health and food industries. Professor Vicic and team will prepare well-defined nickel complexes bearing fluorinated groups in order to systematically determine the experimental conditions that will allow nickel to release the fluorinated groups onto organic scaffolds that are of interest to the pharmaceutical and agrochemical fields. The realization of clean and high-yielding transfers of fluorinated groups to organic substrates is necessary to transform wasteful processes into more sustainable catalytic ones would be of significant value in n both academic and industrial circles. This project will also create a web-based spectral database for fluorinated compounds so that entry into this field can be more accessible to beginning researchers of diverse backgrounds in order to promote a more inclusive workforce. Training graduate students to perform science outreach at surrounding schools is also planned with Lehigh’s Academic Outreach Office. The project will develop methodology on how to access the higher-valent states of nickel under mild conditions using anionic fluoroalkyl nickel complexes that have been developed in the Vicic lab. Next, the Vicic group will work to determine which state is necessary for the release of fluoroalkyl radicals. The team will then identify the scope and selectivity of radical additions to substrates containing alkene and arene functionalities, study the effect of light on the homolysis reactions, and investigate methods to transform catalytic processes into electrocatalytic variants. The team will also prepare a family of anionic nickel precursors bearing organic and fluoroalkyl ligands and monitor the elimination of fluoroalkylated organic products by a variety of analytical techniques. In this way, the effect of oxidants, metal oxidation state, light, and other reaction parameters on reductive elimination at high-valent nickel will be established. The team will also identify strategies to prepare nickel complexes containing chemically and photochemically derivatizable fluorinated groups, and then develop methods for directly preparing libraries of molecules containing such groups for discovery chemistry. These activities are synergistically providing important training in organometallic chemistry and catalysis for a diverse group of graduate and undergraduate students at Lehigh University.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.