CAS: Tuning Deoxyfluorination Reactivity and Selectivity by Coherently Modulating Fluoride-pi Interaction Strength, SNAr Kinetics, and Leaving Group Ability

University Of South Dakota Main Campus, Vermillion SD

Investigators

Abstract

With support of the Chemical Structure, Dynamics & Mechanisms-B program of the Chemistry Division, Professor Haoran Sun of the Department of Chemistry at University of South Dakota is developing next-generation fluorinating reagents that are effective, safe, and economical for the preparation of a broader spectrum of organofluorine compounds of medicinal and material interests. The ultimate goal of this project is to find replacement for dangerous and expensive fluorinating reagents, which will reduce hazardous and environmental safety concerns. The complex nature and multifaceted approaches of this project provide excellent training to postdocs, graduate and undergraduate students for solving challenging problems important to today’s and tomorrow’s societal needs. Involvement of Native American community college students through both workshops and summer research not only attracts underrepresented minority group to STEM, but also helps communicate general science and technology information to their community, which will impact their economic development and wellbeing. Rational design and systematical realization of new fluorinating reagents with tunable reactivity and selectivity for a broader range of substrates remain a significant challenge in organofluorine chemistry. Under this project, Professor Haoran Sun's research group aims to: 1) design and prepare an array of fluorinating reagents with tunable reactivity and selectivity for deoxyfluorination of carboxylic acids, ketones, aldehydes, alcohols, phenols, and epoxides by combining different electron-deficient fluoroaromatics and fluoride salts; 2) understand how the degree of electron-deficiency of these fluoroaromatics affects deoxyfluorination through modulation of fluoride-pi interaction strength, kinetics of the fluoride nucleophilic attack in the rate-determining step, and corresponding leaving group ability; 3) advance fundamental understanding of the correlation between key structure-property factors: molecular electron-deficiency (pi-acidity) scale, fluoride-pi interaction strength, nucleophilic substitution reactivity, leaving group ability, and overall deoxyfluorination reactivity and selectivity; and 4) train students to solve challenging chemistry problems with multifaceted systematic approaches including synthetic, physical organic, and computational chemistries. The results from this project has the potential to provide fundamental chemistry knowledge to other areas of research where ionic species are involved, such as catalysis, energy storage materials, ion transport in biological systems, separation, and sensing. 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.