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Title: Investigation of Mono- and Bisphosphine Ligand Effects in Ni-Catalyzed Cross-Coupling
Authors: Borowski, Julia Elizabeth
Advisors: Doyle, Abigail G
Contributors: Chemistry Department
Keywords: Catalysis
Subjects: Chemistry
Organic chemistry
Issue Date: 2023
Publisher: Princeton, NJ : Princeton University
Abstract: Mechanistically-informed phosphine ligand design for transition metal-catalyzed cross- coupling has enabled the development of robust strategies for C–C and C–heteroatom bond formation. In the case of Pd-catalyzed Suzuki-Miyaura cross-coupling reactions, bulky monodentate phosphines represent the state of the art, promoting the formation of highly active, monoligated catalyst intermediates. Efforts to develop the analogous Ni-catalyzed transformation, however, have revealed that the optimal ligands for Pd do not confer similarly high levels of reactivity for Ni. Moreover, this discrepancy suggests that the distinct reactivity profile of Ni requires a new set of phosphine ligand design principles that have yet to be identified through mechanistic study. This dissertation describes the identification of phosphine ligand structure- reactivity relationships in Ni-catalyzed Suzuki-Miyaura cross-coupling reactions, focusing on the role of catalyst ligation state. The implementation of ligand featurization and data science tools is a powerful strategy for the quantitative study of structure-reactivity relationships across a diverse range of phosphine ligand scaffolds. Chapter 2 describes the use of these tools in tandem with high-throughput experimentation to identify discontinuities in Ni- and Pd-catalyzed cross-coupling datasets as a function of a single monophosphine ligand feature. This feature, which quantifies phosphine steric bulk proximal to the metal center, was found to be the sole readout of catalyst ligation state. Moreover, this analysis combined with organometallic, and computational studies revealed the requirement for the formation of bisligated Ni species to enable successful catalysis. While bisphosphines are commonly used in Ni catalyzed methodologies, thus meeting the bisligated Ni requirement, monophosphines have been found to demonstrate similar or higher reactivity in some cases. Chapter 3 describes the head-to-head comparison of mono- and bisphosphine precatalysts in Ni-catalyzed Suzuki-Miyaura cross-coupling reactions of diverse substrate pairings. Catalytic and mechanistic studies identify the role of monoligated Ni intermediates in accelerating challenging steps of the catalytic cycle, while bisligated Ni intermediates prevent the formation of off-cycle species and catalyst deactivation. These results provide guidelines for ligand selection and establish design principles for the development of optimal ligands for Ni catalysis.
Type of Material: Academic dissertations (Ph.D.)
Language: en
Appears in Collections:Chemistry

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