GOALI: Fluoroalkylation Enabled by Lewis Acids

在药物和农用化合物中，氟原子的存在通常会增强它们的生物活性和稳定性。出于这个原因，许多这些重要的化学品都含有位于这些分子中非常特定位置的氟原子。以这种理想的精度合成氟化分子的方法有限，阻碍了制备新的和更好的化合物的进展。在这个项目中，在化学系化学催化计划的资助下，密歇根大学的Szymczak博士与辉瑞公司的Joseph Tucker博士合作开发了一种新的化学起始材料和反应，将氟引入与药物相关的分子中。这种学术/工业合作正在揭示基本的化学反应，以解决化学合成中的挑战性问题，包括如何利用廉价的含氟原材料。这项工作的成果在农业、医药和氟化工行业产生了广泛的影响。Szymczak博士和Tucker博士积极参与外展活动，以他们的研究为基础，促进学生对科学、技术、工程和数学(STEM)学科的参与。这些活动包括跨越多个机构级别的全国性会议系列，在社区学校的志愿时间和专业知识，以及通过大学研讨会和小组讨论与学生接触，旨在让学生接触STEM职业的广度。在化学系化学催化项目的资助下，密歇根大学的Szymczak博士正在开发以氟烷烃为主要构件的氟烷基化合成方法。这些努力建立在最近的一项发现的基础上，该发现表明，可以合理地选择酸/碱对来促进氟烷烃的活化和转移到与药物相关的分子，其中构建更复杂的CF2-键是主要目标。这项研究项目解决了如何利用来自廉价构件的氟烷基促进C-C键形成反应的化学合成问题：这些反应在药物化学中非常令人垂涎，因为氟化赋予许多药物良好的性质。Goali奖涉及与辉瑞的科学家合作开发可应用于学术和工业部门的集成设计工具。利用高通量反应开发来制备复杂的化学库，该库将氟烷基标签结合到具有明显(区域)选择性的医学相关有机化合物上，从而提供直接访问新分子的途径，从而扩大现有的结构多样性并允许检查结构/功能关系。Szymczak博士和Tucker博士积极参与外展活动，以他们的研究为基础，促进学生对科学、技术、工程和数学(STEM)学科的参与。这些活动包括跨越多个机构级别的全国性会议系列，在社区学校的志愿时间和专业知识，以及通过大学研讨会和小组讨论与学生接触，旨在让学生接触STEM职业的广度。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。

The presence of fluorine atoms in pharmaceutical and agrochemical compounds generally enhances their biological activity and stability. For this reason, many of these important chemicals contain fluorine atoms located in very specific positions within these molecules. Progress in preparing new and better compounds is hindered by the limited number of ways fluorinated molecules can be synthesized with this desirable precision. In this project, with funding from the Chemical Catalysis Program of the Division of Chemistry, Dr. Szymczak of the University of Michigan is working with Dr. Joseph Tucker at Pfizer Corporation to develop a new class of chemical starting materials and reactions to introduce fluorine into pharmaceutically-relevant molecules. This academic/industrial collaboration is uncovering fundamental chemical reactions to address challenging problems in chemical synthesis, including how to utilize inexpensive fluorine-containing raw materials. The results of this work have broad-reaching impact in the agriculture, pharmaceutical and fluorochemical industry. Dr. Szymczak and Dr. Tucker are actively engaged in outreach activities that build upon their research to promote engagement of students in science, technology, engineering and mathematics (STEM) disciplines. These activities, which include a nationwide meeting series across multiple institutional levels, volunteering time and expertise at community schools, and engagement with students through university seminars and panel discussions are directed at exposing students to the breadth of STEM careers. With funding from the Chemical Catalysis Program of the Division of Chemistry, Dr. Szymczak of the University of Michigan is developing fluoroalkylation synthetic methods that use fluoroalkanes as the principle building blocks. These efforts build on a recent discovery showing that acid/base pairs can be rationally selected to promote fluoroalkane activation and transfer to molecules of pharmaceutical relevance, where the construction of more complex –CF2– linkages is a primary goal. This research project addresses the chemical synthesis problem of how to promote C-C bond forming reactions using fluoroalkyl groups derived from cheap building blocks: reactions that are highly coveted in medicinal chemistry because of the desirable properties that fluorination imparts to many pharmaceuticals. The GOALI award involves a partnership with scientists at Pfizer to develop integrated design tools that can be applied across academic and industrial sectors. Use of high throughput reaction development is used to prepare complex chemical libraries that incorporate fluoroalkyl tags onto medicinally relevant organic compounds with distinct (regio)selectivities which provide straightforward access new molecules that expand structural diversity available and allow examination of structure/function relationships. Dr. Szymczak and Dr. Tucker are actively engaged in outreach activities that build upon their research to promote engagement of students in science, technology, engineering and mathematics (STEM) disciplines. These activities, which include a nationwide meeting series across multiple institutional levels, volunteering time and expertise at community schools, and engagement with students through university seminars and panel discussions are directed at exposing students to the breadth of STEM careers.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.