Strategies and Concepts for Enantioselective Electrocatalytic Hydrogenation Reactions

Stanford University, Stanford CA

Investigators

Abstract

With the support of the Chemical Catalysis program in the Division of Chemistry, Professor Robert Waymouth of the Department of Chemistry at Stanford University is using electricity to drive catalytic chemical reactions to make chiral (or "handed") molecules for use as intermediates to agrochemicals or pharmaceuticals. Previously, hydrogen gas has been used to selectively reduce or hydrogenate molecules; in this work, the team at Stanford will use electricity and hydrogen ions to selectively reduce molecules to chiral products. The primary goal is the development of catalysts that are more efficient, longer-lasting, and less wasteful through the application of electrocatalysis. Catalysis is inherently more efficient than stoichiometric transformations, and electrifying catalytic reactions enables the use of electrical energy to drive hydrogenations rather than with high pressures of H2 at high pressures and elevated temperatures.The urgent challenge of discovering new energy-efficient methods for making important molecules for human drugs and agricultural use highlights the critical role that these research and educational experiences will play in the training of the next generation of scientists to address these challenges. Existing partnerships with Gettysburg College, a primarily undergraduate institution, and the Stanford Synchrotron Radiation Lightsource will provide rich opportunities for interdisciplinary training for both graduate and undergraduate students. This program will also support ongoing efforts by graduate students to engage with the broader community, including mentoring high school students in East San Jose. With the support of the Chemical Catalysis program in the Division of Chemistry, Professor Robert Waymouth of the Department of Chemistry at Stanford University is studying new catalysts and patterns of reactivity for catalytic enantioselective electrohydrogenation reactions. The catalytic enantioselective hydrogenation of unsaturated C-C, C-N, and C-O bonds is the most widely practiced catalytic method for the synthesis of optically-active synthetic intermediates essential for agrochemical and pharmaceutical products. Enantioselective electrohydrogenation, utilizing protons and electrons instead of hydrogen, has the potential to electrify this important class of reactions and drive these reactions under ambient conditions using electricity from renewable sources. This project will develop new concepts and strategies for electrocatalytic enantioselective reactions mediated by bifunctional catalysts, guided by the following hypotheses: (1) that utilizing tandem electrocatalytic cycles employing electrochemically regenerable hydride delivery agents can lead to more efficient asymmetric catalysis by bypassing energy-inefficient stepwise multi-electron and -proton transfers; (2) that bifunctional molecular Fe catalysts combined with chiral acids can be adapted for enantioselective electrohydrogenation reactions; (3) and that chiral pincer catalysts with suitable thermochemical and electrochemical properties can be used for tandem electrocatalytic hydride delivery and hydrogenation in water. The importance of enantioselective hydrogenation reactions as one of the major methods for the generation of chiral intermediates highlights the impact of developing new strategies for enantioselective electrohydrogenation to illuminate new scientific principles as well as to provide new opportunities for electrifying a major class of catalytic reactions. 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.