PARTIAL ISOTOPIC LABELING ENABLES DIRECT (LC-)MS ANALYSIS OF REGIOISOMERS AND INSIGHT ON KINETIC ISOTOPE EFFECTS
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Degree type
PhD
Graduate group
Chemistry
Discipline
Chemistry
Subject
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Copyright date
01/01/2025
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Author
Sojdak, Christopher, Anthony
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Abstract
- A method to cleave the C–C biaryl bond of binaphthyl derivatives under reductive conditions is described. Triflic acid employed together with a catalytic HAT reagent, 2-ethyl-9,10-dihydroxyanthracene, that is regenerated using H2 with catalytic Pd/C yielded monomeric products in improved yields. A range of substrates is disclosed, and kinetic analyses provide insight into the mechanism of aryl–aryl activation.2. C–H functionalization of complex substrates is highly enabling in total synthesis and in the development of late-stage drug candidates. Much work has been dedicated to developing new methods as well as predictive modeling to accelerate route scouting. However, workflows to identify regioisomeric products are arduous, typically requiring chromatographic separation and/or nuclear magnetic resonance spectroscopy analysis. In addition, most reports focus on major products or do not assign regioisomeric products which biases predictive models constructed from such data. Herein, we present a novel approach to complex reaction analysis utilizing partial deuterium labels which enables direct product identification via liquid chromatography–mass spectrometry. When combined with spectral deconvolution, the method generates product ratios while circumventing chromatography altogether. Competitive kinetic isotope effects can also be determined. The resultant data is expected to be useful in the construction of predictive models across several dimensions including reaction selectivity, the impact of structure on mechanism, mass spectral ionization patterns, and expedite the identification of drug metabolites.
- Volatile organic compounds (VOCs) are a class of compounds generated by both anthropogenic and biological processes, characterized by their high vapor pressure. Of the naturally produced VOCs alkenes such as isoprene and monoterpenes such as pinene, limonene, and myrcene are the largest components making up 69% and 10% respectively. In the troposphere these alkenes undergo ozonolysis eventually forming hydroxyl radicals via the carbonyl oxide intermediate called a Criegee intermediate. These hydroxyl radicals are a key oxidant in the upper atmosphere as they are responsible for reacting with a variety of greenhouse gases such as nitrous oxides, alkanes, carbon monoxide etc. When reacting with alkanes via hydrogen-atom abstraction the resultant alkyl radicals can uptake oxygen leading to the formation of •QOOH species which further degrade to regenerate hydroxyl radicals. Understanding how these hydroxyl radicals are generated in the upper atmosphere allows for the generation of more robust complete climate models. In order to reliably generate reactive species in a laboratory setting a variety of iodinated alkanes/alkenes as well as alkyl peroxides are required. The synthesis of these materials as well as progress toward unpublished compounds is discussed herein.
Advisor
Kozlowski, Marisa, C
Date of degree
2025