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.

美国国家科学基金会化学部的化学合成项目支持了阿比盖尔·G.普林斯顿大学化学系的道尔说。多伊尔教授和她的学生开发了亲核氟化的新试剂和策略。氟是对公共医疗保健和工业至关重要的无数药物、农用化学品和材料的重要组成部分。然而，选择性地将氟安装到有机分子中的工具要么是有限的，要么在某些情况下是不存在的。具体地，目前用于亲核取代的方法通常依赖于使用传统试剂的苛刻条件，导致对其他官能团的低反应性、选择性和/或耐受性。这项研究导致了新的潜在的催化HF源的发明，一般策略的设计，使温和的和选择性的C-F键的形成，并制备有价值的含氟的氟离子的化学合成。这些策略也适用于合成放射性标记的小分子，用于正电子发射断层扫描（PET），一种重要的诊断工具，用于成像的大脑。该方案支持的学生接受研究、写作、沟通技巧和指导方面的培训。通过各种方案，教授道尔招募和辅导学生从传统上在STEM学科代表性不足的群体。Doyle教授组织了普林斯顿大学学生邀请讲座系列;她和她的学生参加了推广活动，以鼓励早期参与科学。这项研究的重点是开发亲核C-F键形成的新方法，通过从丰富，稳定的氟化物试剂原位生成HF的新策略。这些合成方法利用有机催化或过渡金属催化，提供了高效、温和、选择性和环境友好的路线。Doyle小组和更大的化学界的研究人员能够应用这些方法来构建药物和生物医学领域感兴趣的难以捉摸和理想的化合物。该研究计划还创造了增长的机会，并通过参与多样性研究计划，科学活动中的妇女以及对服务不足社区儿童的外联活动，促进了科学中代表性不足群体的进步。

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.