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

CAS：通过连贯调节氟化物-π 相互作用强度、SNAr 动力学和离去基团能力来调节脱氧氟化反应性和选择性

• 批准号: 2247635
• 负责人: Haoran Sun
• 金额: $ 51.28万
• 依托单位: University of South Dakota Main Campus
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2247635&HistoricalAwards=false
• 关键词: CAS; Tuning; Deoxyfluorination; Reactivity; Selectivity

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.

南达科他州大学化学系孙浩然教授在化学系化学结构、动力学机制-B项目的支持下，正在开发新一代氟化试剂，这些试剂有效、安全、经济，可用于制备更广泛的药用和材料用途的有机氟化合物。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，这将减少危险和环境安全问题。 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良好的培训，以解决对当今和未来社会需求至关重要的挑战性问题。美国原住民社区大学学生通过研讨会和暑期研究的参与不仅吸引了代表性不足的少数群体到STEM，而且还有助于向他们的社区传播一般科学和技术信息，这将影响他们的经济发展和福祉。合理设计和系统实现新的氟化试剂，具有可调的反应性和选择性，为更广泛的底物仍然是一个重大的挑战，在有机氟化学。在本项目下，孙浩然教授的研究小组的目标是：1）通过组合不同的缺电子氟代芳烃和氟化物盐，设计和制备一系列对羧酸、酮、醛、醇、酚和环氧化物的脱氧反应具有可调反应活性和选择性的氟化试剂; 2）理解这些氟代芳族化合物的缺电子程度如何通过调节氟化物-π相互作用强度来影响脱氧麻黄碱，速率决定步骤中氟化物亲核攻击的动力学和相应的离去基团能力; 3）推进对关键结构-性质因素之间的相关性的基本理解：分子缺电子（π-酸度）标度、氟化物-π相互作用强度、亲核取代反应性、离去基团能力和总体脱氧核苷反应性和选择性;培养学生运用合成化学、物理化学、有机化学和计算化学等多方面的系统方法解决具有挑战性的化学问题。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础化学知识，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，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。