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

在化学系化学结构、动力学和机理B项目的支持下，南达科他大学化学系孙浩然教授正在开发有效、安全和经济的新一代氟化试剂，用于制备更广泛的具有医药和材料价值的有机氟化合物。该项目的最终目标是找到危险和昂贵的氟化试剂的替代品，从而减少对危险和环境安全的担忧。该项目的复杂性和多方面的方法为博士后、研究生和本科生提供了极好的培训，以解决对当今和明天的社会需求至关重要的挑战性问题。美洲原住民社区大学生通过研讨会和暑期研究的参与，不仅吸引了代表不足的少数群体来到STEM，还有助于向他们的社区交流一般的科学和技术信息，这将影响他们的经济发展和福祉。合理地设计和系统地实现对更广泛底物具有可调反应活性和选择性的新型氟化试剂仍然是有机氟化学中的一个重大挑战。在这个项目下，孙浩然教授的研究小组的目标是：1)通过结合不同的缺电子含氟芳烃和氟盐，设计和制备一系列对羧酸、酮、醛、醇、酚和环氧化物的脱氧氟化反应活性和选择性可调的氟化试剂；2)了解这些含氟芳烃的缺电子程度如何通过调节氟化物-pi相互作用强度、决定速率步骤中氟化物亲核攻击的动力学和相应的离开基团能力来影响脱氧氟化反应；3)加深对关键结构-性质因素之间的关系的基本理解：分子电子缺失(pi-酸性)标度、氟化物-pi相互作用强度、亲核取代反应能力、离开基团能力以及整体脱氧氟化反应和选择性；以及4)训练学生用多方面的系统方法解决具有挑战性的化学问题，包括合成化学、物理有机化学和计算化学。该项目的成果有可能为涉及离子物种的其他研究领域提供基本的化学知识，如催化、储能材料、生物系统中的离子传输、分离和传感。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.