α-Hydroxy C–H Functionalization of Alcohols via Boronic Acid, HAT, Photoredox Triad Catalytic System
Author ORCID Identifier
Semester
Fall
Date of Graduation
2024
Document Type
Dissertation
Degree Type
PhD
College
Eberly College of Arts and Sciences
Department
Chemistry
Committee Chair
Brian Popp
Committee Co-Chair
Margaret Hilton
Committee Member
Brian Dolinar
Committee Member
Hacer Karatas Bristow
Committee Member
Werner Geldenhuys
Abstract
This dissertation explores the research that I have conducted in my time at West Virginia University. Most of my work has focused on the development of methods and studies to further understand the α-OH C–H functionalization of alcohols. This work involves a system of catalysts including photocatalysts, HAT catalysts, and boronic acid catalysts. Chapter 1 highlights a background for each of these areas. Photoredox catalysis has been an increasing area of chemistry over the past two decades as this technique can be used to design conditions to form new bonds in a selective manner through the utilization of light energy. HAT catalysis is another rising area of chemistry that forms reactions through radical pathways rather than traditional chemical pathways where reactions are completed through electrons moving as pairs. HAT works by abstracting a hydrogen from a generally inert C–H bond to selectively functionalize the substrate. Boron reagents have been used in a variety of ways to induce the reactivity of alcohol substrates. This is mainly due to the high exchange rate between B–O bonds, which allows for boron oxide catalysts to react with alcohols to form boron esters. While in the boron ester state, additional reagents can be applied to alter the substrate. These techniques have been combined to explore the α-OH C–H functionalization of alcohols through the application of photocatalysis, HAT catalysis, and boronic acid catalysis.
Chapter 2 explores the α-OH C–H functionalization of diols. In this chapter, a method was developed to selectively alkylate the α-OH position of diols with arylboronic acids, quinuclidine, and phtotcatalysis. The mechanism of this reaction proceeds through the abstraction of the α-OH C–H bond of the activated boronate complex formed between the diol, boronic acid, and quinuclidine. Through kinetic analysis, this reaction is observed to be faster with reduction of electron density of arylboronic acids. 1H and 11B NMR experiments indicate that the difference in reaction rates is caused by a more labile equilibrium with the use of electron-poor boronic acids.
Chapter 3 explores the α-OH C–H alkylation of mono-alcohols and how they compare to diols by applying the method developed in Chapter 2. Direct competition shows that the reaction is selective for diols over both primary and secondary mono-alcohols. 1H NMR experiments showed that this is due to a higher binding affinity of the boronic acid to the diol compared to the mono-alcohol. Kinetic analysis shows that the α-OH C–H alkylation of mono-alcohols is increased with the use of electron-poor arylboronic acids, which is again proposed to be due to the difference in equilibrium as indicated by 11B and 1H NMR analysis. A small substrate scope was explored for this reaction, which presents functional group tolerance for a variety of more complex primary mono-alcohols.
Chapter 4 combines the work of the Hilton and Popp groups by exploring the α-OH C–H alkylation of alcohols with ß-carboxyboronic acids. It was hypothesized that these bifunctional boronic acids would form an active substrate-boronate ester in a more favorable manner due to the inclusion of the Lewis basic site on the boronic acid. ß-carboxyboronic acids are applicable to the alkylation of both diols and primary mono-alcohols. Kinetic studies show that the application of ß-carboxyboronic acids significantly increases the reaction rate for primary mono-alcohols compared to the application of arylboronic acids. Additionally, the yield of alkylation for primary mono-alcohols is increased with the use of ß-carboxyboronic acids. NMR studies with both diols and mono-alcohols indicate the formation in the active boronate species as the major species due to the presence of distinct signals in both 11B and 1H spectra. This is different from what is observed with arylboronic acids where multiple species are observed via NMR analysis. Because of the increased rate of alkylation, increased overall yield, and presence of one species observable by NMR, it is proposed that the formation of the active boronate species is more favorable with the utilization of ß-carboxyboronic acids compared to arylboronic acids.
Recommended Citation
Cowan, Seth Christopher, "α-Hydroxy C–H Functionalization of Alcohols via Boronic Acid, HAT, Photoredox Triad Catalytic System" (2024). Graduate Theses, Dissertations, and Problem Reports. 12651.
https://researchrepository.wvu.edu/etd/12651