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.
