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Title: The Direct β-Activation of Aldehydes and Ketones via Photoredox Organocatalysis: Discovery, Scope, and Mechanism
Authors: Pirnot, Michael Thomas
Advisors: MacMillan, David W. C.
Contributors: Chemistry Department
Keywords: Catalysis
Mechanistic Investigations
Photoredox Catalysis
Subjects: Chemistry
Issue Date: 2014
Publisher: Princeton, NJ : Princeton University
Abstract: The discovery of activation modes within synthetic chemistry has enabled the development of a myriad of transformations. This thesis details the discovery of a new activation mode that allows for the direct beta-functionalization of carbonyl species, such as aldehydes and ketones, through the synergistic merger of amine and visible light photoredox catalysis. This novel mode of reactivity is particularly attractive for the functionalization of ketones or aldehydes at the beta-position has generally been an elusive transformation. This protocol was successfully executed with electron-deficient benzonitriles to afford beta-aryl ketones and aldehydes with a broad scope for both the aryl and carbonyl coupling partner. The development of an asymmetric variant has yielded promising results; unfortunately, racemization studies have indicated that the beta-aryl product undergoes rapid deprotonation to ablate the stereochemistry set during the stereoselective carbon-carbon bond formation step. Mechanistic studies into this protocol have provided several key insights. Computational studies have aided in recognizing the selective preference for beta-deprotonation over alpha-deprotonation of the enamine radical cation. Similarly, computation has supported radical-radical coupling as the likely mechanism for carbon-carbon bond formation. Electron paramagnetic resonance (EPR) studies have provided evidence for the persistence of the radical anion of 1,4-dicyanobenzene, which also lends support to a radical-radical coupling mechanism. DABCO has also been recognized as an effective electron transfer catalyst through spectroscopic studies, which explains the superiority of this base in the chemical protocol. Lastly, extensive kinetic and isotope labeling experiments indicate that beta-deprotonation of the enamine radical cation is the turnover-limiting step. Together, these results have provided a better fundamental understanding of this complex mechanism.
Alternate format: The Mudd Manuscript Library retains one bound copy of each dissertation. Search for these copies in the library's main catalog
Type of Material: Academic dissertations (Ph.D.)
Language: en
Appears in Collections:Chemistry

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