CAS: Stereoselective Nickel-Catalyzed Olefin Coupling Methods for the Sustainable Preparation of Complex Molecules

University Of North Carolina At Chapel Hill, Chapel Hill NC

Investigators

Abstract

With the support of the Chemical Synthesis Program in the Division of Chemistry, Professor Simon Meek at the University of North Carolina at Chapel Hill is studying the development of sustainable coupling methods for the preparation of complex molecules. Demand for chemical processes that economically and selectively prepare organic compounds is critical to sustainable manufacturing and future breakthroughs in drug discovery. In this project, Professor Meek is tackling these challenges by developing complexity-building protocols that efficiently and selectively assemble multiple chemical components in a single operation. These protocols leverage readily available unsaturated hydrocarbons and common chemical groups with reactions driven by catalysts (additives that make reactions more efficient and/or faster) made from nickel. Through designing new catalysts, Professor Meek and his team are unlocking the conversion of unsaturated hydrocarbons into useful intermediates, and their transformation into high-value compounds. Professor Meek's group is actively involved in outreach initiatives that extend the scope of his research, delving into crucial subjects pertinent to both undergraduate and graduate education. These endeavors highlight the transformative influence of sustainability, organic chemistry, and catalysis on everyday life. By amplifying the involvement of undergraduate students from varied backgrounds and integrating comprehensive educational elements into courses across different levels, Professor Meek aims to enrich STEM education for all students and cultivate nurturing environments conducive to empowering the scientists of tomorrow. In this project, funded by the Chemical Synthesis Program, Dr. Meek and his team of graduate and undergraduate students at the University of North Carolina at Chapel Hill, develop new sustainable nickel-catalyzed coupling methods for the stereoselective synthesis of complex organic molecules. These transformations unlock efficient, site- and stereo-controlled multicomponent reactions of simple carbonyl-type electrophiles and readily available unsaturated hydrocarbons leading to the formation of two new bonds and up to three new stereocenters. Molecular assembly is catalyzed by phosphine-nickel complexes that display high reactivity and selectivity, characteristics essential to efficient and economical manufacture of important functionalized acyclic and cyclic molecular scaffolds. Fundamentally, these reactions leverage the diverse chemical reactivity of organonickel intermediates with an array of nucleophilic coupling partners. Overall, this synthetic tactic is enabling the formation of tertiary and quaternary carbon stereocenters, in addition to amine, alcohol, and heterocycle functionality. Moreover, this research opens new avenues for chiral ligand and catalyst design with abundant transition metals that is of importance to both industry and academia. 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.