New Perspectives: I. 13C NMR Spectroscopy for the Quantitative Determination of Compound Ratios; II. Evidence That Additions of Grignard Reagents to Aliphatic Aldehydes Do Not Involve Single-Electron-Transfer Processes

• Main Author: Otte, Douglas A
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-2016
• Subjects: Analytical chemistry; Organic chemistry
• ISBN: 9781339950723; 1339950723

The ability to predict the outcomes of experiments is an important skill for any scientist. To predict the outcomes of chemical reactions, one must first understand the mechanisms by which the reactions proceed. This dissertation makes contributions to two germane subjects that have garnered significant attention, by approaching both topics from unique perspectives. Chapter One reassess the utility of 13C NMR spectroscopy as a tool for determining compound ratios. Compound ratios can provide insight into the relative thermodynamic stabilities or rates of formation of reaction products, affording information that is often critical to the determination of reaction mechanisms. 13C NMR spectroscopy is often overlooked as a quantitative tool for determining these compound ratios because scientists view it as a time-intensive, and therefore costly, technique. Techniques such as 1H NMR spectroscopy and chromatography, however, are often inadequate for determining the ratios of closely related molecules (e.g., diastereomers with stereocenters separated by four atoms) due to signal overlap and coelution. In this Chapter, 13C NMR spectroscopy has been shown to be effective at determining compound ratios of closely related molecules, even when short relaxation delays are employed. The technique is complementary to 1H NMR spectroscopy and chromatography, and is most useful when these other techniques are either inadequate or ineffective. In addition, molecular oxygen has been successfully employed as a non-contaminating paramagnetic relaxation agent for obtaining compound ratios of unrelated molecules by 13C NMR spectroscopy with short relaxation delays. Chapter Two offers some clarity to a 115 year old conversation replete with ambiguity. The mechanism of addition of Grignard reagents to carbonyl compounds is highly complex, with much evidence supporting both single-electron transfer (SET) and polar mechanisms. Much of this complexity is a result of the interplay between and the nature of the Schlenk equilibrium, substrate, and reagent. Although much attention has been focused on the mechanism of addition of Grignard reagents to aromatic carbonyl compounds, little attention has been paid to understanding the mechanism of addition to aliphatic carbonyl compounds. In this Chapter, the mechanism of addition of Grignard reagents to aliphatic aldehydes has been shown to be effectively concerted, with no evidence supporting a SET-based mechanism. To make this determination, the diphenylcyclopropylcarbinyl radical clock (one of the fastest radical clocks known, with a rate of ring-opening rearrangement of 5 x 1011 s–1) was employed. Initial efforts focused on the mechanism of addition of allylmagnesium reagents, and the study was expanded to include other Grignard reagents, including reagents that are known to participate in SET processes. Finally, evidence is presented that the analogous Barbier reaction, which is believed to involve the in situ generation of a Grignard reagent, also proceeds by a polar mechanism in organic solvents.