Methods for Late-Stage Nucleophilic Fluorination and Radiofluorination

后期亲核氟化和放射性氟化的方法

• 批准号: 1565983
• 负责人: Abigail Doyle
• 金额: $ 45万
• 依托单位: Princeton University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1565983&HistoricalAwards=false
• 关键词: Methods; Late; Stage; Nucleophilic; Fluorination

The Chemical Synthesis Program of the NSF Chemistry division supports the research of Professor Abigail G. Doyle of the Department of Chemistry at Princeton University. Professor Doyle and her students develop new reagents and strategies for nucleophilic fluorination. Fluorine is an essential constituent of myriad drugs, agrochemicals and materials that are crucial to public healthcare and industry. However, the tools to selectively install fluorine into organic molecules are either limited or in some cases nonexistent. Specifically, current methods for nucleophilic fluorination often rely on harsh conditions with traditional reagents resulting in low reactivity, selectivity and/or tolerance to other functional groups. This research leads to the invention of new latent HF sources for catalysis, the design of general strategies that enable mild and selective C-F bond formation, and the preparation of valuable fluorine-containing synthons for chemical synthesis. These strategies are also adapted for the synthesis of radiolabeled small molecules for use in positron emission tomography (PET), an important diagnostic tool for imaging the brain. The students supported under this program receive training in research, writing, communication skills, and mentoring. Through various programs, Professor Doyle recruits and mentors students from groups traditionally underrepresented in the STEM disciplines. Professor Doyle organizes the Princeton University Student Invited Lecture Series; she and her students participate in outreach activities to encourage early engagement in the sciences.The key focus of this research is the development of new methods for nucleophilic C-F bond formation enabled by novel strategies for in situ generation of HF from abundant, stable fluoride reagents. These synthetic methods offer routes that are efficient, mild, selective, and environmentally benign, utilizing either organocatalysis or transition metal catalysis. Researchers in the Doyle group and in the greater chemical community are able to apply these methods to construct elusive and desirable compounds of interest to the pharmaceutical and biomedical fields. This research program also creates opportunities for growth and promotes the advancement of underrepresented groups in the sciences through participation in diversity research programs, women in science events, and outreach activities to children from underserved communities.

NSF化学部的化学合成计划支持普林斯顿大学化学系的Abigail G. Doyle教授的研究。 Doyle教授和她的学生开发了新的试剂和亲核氟化策略。氟是对公共医疗保健和工业至关重要的众多药物，农产品和材料的重要组成部分。但是，选择性地将氟安置到有机分子中的工具是有限的，或者在某些情况下不存在的工具。具体而言，当前的亲核氟化方法通常依赖于传统试剂的恶劣条件，导致反应性低，选择性和/或对其他官能团的耐受性。这项研究导致了新的潜在HF来源进行催化的发明，可以实现轻度和选择性的C-F键形成的一般策略的设计以及为化学合成的有价值的含氟合成的合成。这些策略还适用于合成放射性标记的小分子以用于正电子发射断层扫描（PET），这是用于成像大脑的重要诊断工具。根据该计划支持的学生接受了研究，写作，沟通技巧和指导的培训。通过各种计划，Doyle的新兵教授和来自STEM学科中人数不足的团体的学生。道尔教授组织普林斯顿大学学生邀请的讲座系列； 她和她的学生参加了宣传活动，以鼓励早期参与科学。这项研究的重点是开发新方法的新方法是由新颖的策略通过丰富，稳定的氟化物试剂来实现HF的新型策略来实现的。这些合成方法提供了使用器官分析或过渡金属催化的高效，温和，选择性和环境良性的途径。 Doyle组和大化学界的研究人员能够应用这些方法来为药物和生物医学领域构建难以捉摸且可取的感兴趣的化合物。该研究计划还通过参与多样性研究计划，科学事件中的妇女以及向来自服务不足社区的儿童参加多样性研究计划，促进科学中代表性不足的群体的发展机会。

项目成果

Nucleophilic (Radio)Fluorination of Redox-Active Esters via Radical-Polar Crossover Enabled by Photoredox Catalysis

通过光氧化还原催化实现的自由基-极性交叉对氧化还原活性酯进行亲核（放射性）氟化

• DOI: 10.1021/jacs.0c03125
• 发表时间: 2020
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Webb, Eric W.;Park, John B.;Cole, Erin L.;Donnelly, David J.;Bonacorsi, Samuel J.;Ewing, William R.;Doyle, Abigail G.
• 通讯作者: Doyle, Abigail G.