Tracking Organogold Intermediates in Heterocycle Synthesis Toward Designing Highly Active and Systematically Tunable Gold(I) Catalysts

With the support of the Chemical Mechanism, Function, and Properties Program of the Division of Chemistry, Professor Amanda Jones of the Department of Chemistry at Wake Forest University is examining the fundamental reactivity associated with phosphine based gold(I) catalysts. The work seeks to improve catalytic processes by collecting quantitative data needed to design tunable and improved conditions for achieving an array of synthetically valuable organic transformations. The project will train undergraduate and graduate students in chemistry techniques and research project design, setting them up for successful future careers in science. The project will also contribute foundational knowledge that will empower chemists to develop more efficient and economical tools for making molecules with important medicinal and materials applications. Phosphine supported gold(I) catalysts demonstrate versatile properties for achieving an array of disparate transformations, often back-to-back in one reaction flask, but they can be limited by instability and low reactivity. Mechanistic studies of these reactions have revealed that complexities can be both hurdles and opportunities, and continued effort is needed to optimize their use and achieve their maximum potential. This project will measure kinetics of alkene hydroamination to clarify mechanism ambiguities, synthesize new phosphorous based ligands to enhance gold Lewis acidity while maintaining stability, and use an alkyne cyclization reaction to determine the role of non-traditional solvents on the evolution of organogold intermediates to build a better theoretical framework for explaining observed media effects. The central hypothesis is that electron deficient ligands present untapped potential for expanding the scope of catalytic reactions, despite historic use of strong electron donor ligands. Gold(I) catalysts supported by such electron withdrawing ligands traditionally suffer from facile decomposition; the team will design ligands to increase Lewis acidity while maintaining stability in the corresponding catalysts. 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.