Diverse and Selective Catalytic P–C Bond Formation

University Of Vermont & State Agricultural College, Burlington VT

Investigators

Abstract

With the support of the Chemical Catalysis program in the Division of Chemistry, Professor Rory Waterman of the University of Vermont will study catalysis that promotes formation of phosphorus-carbon bonds. Phosphorus-carbon bonds appear in all living things, are in consumer goods, and are even present in some of the COVID-19 vaccines, among other pharmaceutical agents. However, methods to prepare molecules containing this element are limited, particularly those that are catalytic. Catalysis can create efficiencies in both resource utilization and synthesis that would aid in the challenges with phosphorus. As such, this project aims to deliver a new generation of faster, more efficient, and better controlled catalysts that use phosphorus, benefitting researchers in a range of fields. These efforts have the potential to have a large impact for the synthesis molecules related to biomedical science and chemical biology. Another more ambitious aim of the project is to use catalysis to generalize a rare but very efficient phosphorus-carbon bond forming reaction. The project also aims to establish light as an energy source for phosphorus-carbon bond forming catalysis, so-called photocatalysis, and understand how this photocatalysis operates to facilitate its expansion to catalytic reactions with other elements. Professor Waterman has a strong history of involving high school students from historically underrepresented groups in NSF-funded research and will use this project to increase capacity to involve pre-college students in research, helping to meet long-standing workforce development goals. In this research, Professor Rory Waterman of the University of Vermont will study catalysis that promotes P-C bond formation from both P(III) and P(I), improved enantioselectivity in hydrophosphination, and expand photocatalytic hydrophosphination. The project builds on an initial discovery that photocatalytic hydrophosphination is general and aims to unravel the mechanisms that unfold for both early and late transition metal catalysts. This effort compliments innovations in bench-stable hydrophosphination catalysis. The project will also combine these efforts to investigate enantioselective hydrophosphination catalysts for unactivated substrates, potentially availing hydrophosphination as a late-stage synthetic tool in the synthesis of complex molecular architectures, particularly those scaffolds that are likely to engender biological activity. Additional efforts in the project aim to leverage cyclophosphines as P(I) precursors via catalysis with an eye toward controlling singlet phosphinidene formation. Cyclophosphines can also be primary phosphine precursors, and this understanding will aid in the expansion of hydrophosphination catalysis through expansion of phosphine substrates. These efforts are directed at making an end-run around limitations in hydrophosphination and phosphinidene transfer. This work holds promise to advance fundamental understanding of catalysis in P-C bond formation, with potential application to other catalytic systems. Additionally, many specific catalytic reactions targeted in this study have the potential for much broader application in the larger synthetic chemistry community. 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.