Nickel-Catalyzed Three-Component Cross-Coupling with Unactivated Alkenes

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The efficient conversion of renewable chemical feedstocks into valuable products, such as medicines, agricultural chemicals, and other materials, is a central challenge in modern synthetic chemistry research. Alkenes (molecules that contain a carbon-carbon double bond (C=C) bond) are one class of feedstocks that are ubiquitous, inexpensive, and available on large scale. While alkenes have been long appreciated as important starting materials for the synthesis of valuable substances, at present it remains difficult for chemists to convert alkenes into many types of desirable products. In this project, Dr. Keary M. Engle is developing new reactions to fill this gap. Specifically, by using small quantities of an inexpensive, non-toxic, and earth-abundant nickel catalyst, Dr. Engle's reactions are allowing alkenes to be used as lynchpins to connect to two additional reactants, allowing for the formation of otherwise difficult to form carbon-carbon single bonds bonds between the reactants and the alkenes. Dr. Engle and his research team are highly engaged in outreach activities that are synergistic with his research in order to promote engagement with science, engineering, and mathematics (STEM) disciplines among diverse populations. Specifically, these efforts include internships for high school and undergraduate students, open-access sharing of research-relevant information for scientists and for the general public, and implementation of active-learning strategies for classroom teaching. This research project helps to improve the sustainability and innovation of the chemical industry while increasing the technical workforce of the United States.With funding from the Chemical Catalysis Program of the Chemistry Division, Dr. Keary M. Engle of The Scripps Research Institute is developing a toolkit of nickel-catalyzed, three-component, cross-coupling reactions to convert alkenes into structurally complex products that have potential utility in academia and industry. In particular, the Engle lab is developing transformations that strategically employ proximal chelating functional groups to control the key elementary steps and enhance selectivity for a desired 1,2-difunctionalization of alkenes. Detailed mechanistic studies combining reaction kinetics, organometallic synthesis, and density functional theory (DFT) are being carried out to elucidate the reactivity of key organonickel intermediates involved in these catalytic processes. By drawing on these mechanistic insights, Dr. Engle is translating existing auxiliary-based approaches to new strategies that take advantage of native functional groups for directivity, in order to improve the efficiency, utility, and atom-economy of such reactions. A diverse collection of reaction partners are being examined, including those capable of forming challenging C(sp3)-C(sp3) and C(sp3)-heteroatom linkages. Dr. Engle and his research group are actively engaged in STEM outreach programs, including high school and undergraduate internship programs, as well as disseminating scientific knowledge to diverse audiences through various media platforms and through innovative classroom teaching initiatives.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.