Lewis Base Directed Intermolecular Hydrogen Atom Transfer

With support from the Chemical Synthesis Program in the Division of Chemistry, Professor Thomas Lectka of Johns Hopkins University is studying new ways to selectively modify one carbon-hydrogen bond in a complex molecule that features many carbon-hydrogen bonds. These types of reactions are important for systematically altering biologically active molecules to study their reactivity without having to build each individual molecule from scratch.

Professor Lectka and his research team are determining how loci in a complex molecule interact with a carbon-hydrogen bond-activating agent and using this information to predict and improve the ability to choose a single carbon-hydrogen bond for activation. The carbon-hydrogen bonds in these studies are being converted to carbon-fluorine, carbon-bromine, carbon-oxygen, and carbon-nitrogen bonds, valuable C-H activation transformations in organic synthesis.

Professor Lectka is also partnering with the JHU Women in Science and Engineering (WISE) program and the JHU-NSF STEM Achievement in Baltimore Elementary Schools (SABES) program to provide research experiences for local high school students.

Site-selective C-H functionalization in complex molecular settings is a current grand challenge motivated by the desire to be able to study and modify natural products and pharmaceutical targets without having to individually prepare each analogue from basic building blocks. Professor Lectka and his research group are investigating a new approach to this problem through the development of hydrogen-atom transfer reagents that can specifically coordinate to a substrate and selectively activate a single carbon-hydrogen bond for C-X bond formation.

Simultaneously, this team is also exploring the types of functional groups beyond ketones and enones that can influence the selectivity of the hydrogen-atom transfer reagents and determining the effect of substrate coordination to metal additives. These activities are providing a strong training platform for the professional development of graduate students and research experiences for undergraduate students.

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.