Development and Mechanistic Elucidation of Carbonyl-Olefin Metathesis Transformations
Vonesh, Hannah
2022
Abstract
Olefin–olefin metathesis has drastically changed how olefins are synthesized in materials, agrochemicals, and pharmaceuticals. An important variation of olefin–olefin metathesis is carbonyl–olefin metathesis, which provides an additional approach to access olefins, but has lacked advancements in methodology. In the last decade, the development of catalytic protocols for carbonyl–olefin metathesis has brought a renewed interest to field. The current proposed catalytic cycle for FeCl3-catalyzed intramolecular ring-closing carbonyl–olefin metathesis from Schindler and co-workers in 2017 operates through an asynchronous, concerted [2+2]-cycloaddition, forming a reactive oxetane intermediate. The Lewis acid-bound oxetane fragments via retro-[2+2]-cycloaddition to furnish the desired metathesis product and a carbonyl byproduct. This work has been expanded to new reaction paradigms, including intermolecular ring-opening and cross carbonyl–olefin metathesis variants, as well as other Lewis acid-catalyzed interrupted carbonyl–olefin metathesis transformations. Recently, new mechanistic proposals for Lewis acid-catalyzed carbonyl–olefin metathesis have been published in the literature, and in collaboration with Merck & Co. the Schindler group reinvestigated the reaction. Chapter 1 details the known reactivity modes for Lewis and Brønsted acids with carbonyls and olefins from their very beginnings; focused initially on carbonyl-ene and Prins chemistry, followed by the more recently discovered reactivity with carbonyl–olefin metathesis and interrupted carbonyl–olefin metathesis. Chapter 2 describes the first report of intermolecular ring-opening carbonyl–olefin metathesis between cyclic olefins and carbonyls. The reaction exclusively yields one of two metathesis products, further mechanistic investigations reveal that the transformation proceeds through a single regioisomeric oxetane to provide unsaturated ketones. A competing carbonyl-ene pathway provides two additional products. Chapter 3 investigates the superelectrophilic FeCl3/AgBF4 ion pair-catalyzed cross carbonyl–olefin metathesis of aldehydes and tri-substituted olefins. The reaction exclusively yields (E)-olefin products, one of three possible metathesis products. Independently synthesized oxetane intermediates were used to study the selectivity in key mechanistic step, and only a single regio- and diastereomeric oxetane provides the observed metathesis product. Chapter 4 outlines the synthesis of pentalenes, indenes, naphthalenes, and azulenes from cyclic, aliphatic ketones via a new reactivity mode of carbonyls and olefins. A distinct Lewis acid-catalyzed interrupted carbonyl–olefin metathesis furnishes the interesting bicyclic products. Lastly, Chapter 5 details the extensive mechanistic elucidation and revision of FeCl3-catalyzed intramolecular ring-closing carbonyl–olefin metathesis. Experimental 13C kinetic isotope effects (KIEs), beta-secondary deuterium KIEs, Hammett studies, and explicit solvent calculations all correspond to a stepwise addition mechanism, rather than an asynchronous, concerted [2+2] mechanism. This unique combination of 13C natural abundance KIEs and explicit solvent molecular dynamics calculations reveals a common failure mode in routinely used implicit solvent calculations that can lead to incorrect predictions of charged intermediates along reaction pathways.Deep Blue DOI
Subjects
carbonyl-olefin metathesis Lewis acid catalysis 13C natural abundance kinetic isotope effects explicit solvent molecular dynamics
Types
Thesis
Metadata
Show full item recordCollections
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.