Development of New Diaryl Diazo Compounds and the Study of their application in C-H Functionalization Chemistry Restricted; Files Only
Lee, Maizie (Summer 2023)
Abstract
This dissertation is divided into four chapters discussing the work conducted throughout my tenure in the Davies group.
Chapter One is an overview of dirhodium catalyst development over the past decade, and the impact this has had on C-H Functionalization strategies. A review Dirhodium catalysts and their applications is discussed.
Chapter Two focuses on the background of diazo compounds and their reactivity. Previous work on donor/donor systems in discussed and examples of diaryl diazo carbenes including their applications in natural product synthesis are disclosed. Based on these precedence, new diaryl diazo compounds were synthesized and a systematic study comparing their reactivity to that of donor/acceptor carbenes is described. The key findings of this chapter are that diaryl diazo compounds exhibit similar electronics of a push/pull donor/acceptor system; and compounds with sterically bulky ortho substituents can behave with high diastereo- and enatio- control.
Chapter Three leverages the findings of chapter two regarding the reactivity of diaryl diazo compounds to generate triarylmethanes with high levels of asymmetric induction. The C–H insertion of 1,4 cyclohexadiene then oxidation lead to a variety of triarylmethane compounds. This work demonstrates the first examples of an asymmetric intermolecular C–H insertion with diaryl diazo compounds, and provides more evidence for diaryl diazo compounds being in an extended class of donor/acceptor carbenes.
Chapter Four investigates the strategies used to generate diazo compounds. In collaboration with the Stahl group at University of Wisconsin, Madison a catalytic aerobic oxidation of hydrazones to diazo compounds is disclosed. This method is amendable to flow conditions, making it an attractive method for industry. Follow up studies use heterogenous M-N-C catalyst to achieve the in tandem oxidation of hydrazones to diazo compounds then C–H functionalization.
Table of Contents
Table of Contents
Chapter One. Dirhodium Carbene Chemistry and Diazo Compounds 1
1.1 Introduction 1
1.2 Metal Carbene Complexes 2
1.3 Dirhodium Catalysts for Highly Selective C-H Functionalization Reactions 4
1.4 Next Generations of Chiral Rhodium Catalysts 7
1.5 Select Examples of C-H Functionalization using Donor/Acceptor Diazo Compounds 11
1.6 Bedaquiline Synthesis and Donor/Donor Hypothesis 13
1.7 Conclusions 15
1.8 References 16
Chapter 2. Study and Evaluation of Diaryl Diazo Compounds as Pseudo Donor/Acceptor Carbene Compounds 20
2.1 Background and Previous Work on Diaryl Diazo Compounds 20
2.2 Diaryl Diazo Compounds as Pseudo Donor/Acceptors 26
2.3 Experimental Studies 29
2.4 Computational studies 36
2.5 Kinetic studies via ReactIR 38
2.6 Conclusion 40
2.7 Experimental Data 42
2.7.1 General Considerations 42
2.7.2 General Procedure for Diazo Compounds 43
2.7.3 General procedure for cyclopropanation: 47
2.7.4 Crude NMR for d.r. determination 57
2.7.5 1H and 13C NMR 75
2.8 HLPC Spectra for Enatnioselective Determination 85
2.8 X-Ray Crystal Structure 99
2.9 References 102
Chapter 3. C–H Functionalization Chemistry using Diaryl Diazo Compounds and their Application
Toward Triarylmethane Compounds 106
3.1 Introduction of Intermolecular Reactivity of Diaryl Diazo Compounds 106
3.2 Preliminary Results and Discussion of C–H Insertion 107
3.3 Background of the Synthesis and Utility of Triarylmethane Compounds 110
3.4 Synthetic Studies and Results 112
3.4 Conclusions 120
3.5 Experimental Procedures and Data 122
3.5.1 General Considerations 122
3.5.2 Preparation of diaryl/heteroaryl diazo compound 123
3.5.3 General procedures 125
3.6. 1H 13C and 19F NMR Spectra for Characterization of Compounds. 147
3.7 X-Ray Crystallographic Data for Compound 20a. 176
3.8 HPLC Spectra for Enantioselectivity Determination 178
3.9 References 207
Chapter 4. Oxidation of Hydrazones to Diazo Compounds- Strategies and Flow Conditions 209
4.1 Introduction of Diazo Synthesis Strategies 209
4.2 Hydrazone Oxidation of Diazo Compounds: Initial Work by Davies and Stahl Labs 210
4.3 Oxidation of Diaryl Hydrazone to Diazo Compounds Results and Discussion 212
4.4 Heterogeneous Metals on Nitrogen-Doped Carbon- Oxidation and Flow Applications 216
4.5 Heterogeneous MNC Results and Discussion 217
4.6 Conclusions 224
4.7 Experimental Data 226
4.7.1 General Considerations 226
4.7.2 General Procedure for Diaryl Hydrazone Oxidation 227
4.8 HPLC Spectra for Enatnioselective Determination 237
4.9 References 245
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File download under embargo until 16 August 2025 | 2023-08-03 12:34:39 -0400 | File download under embargo until 16 August 2025 |
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