GOALI: Fluoroalkylation Enabled by Lewis Acids

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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.