Development of New Diaryl Diazo Compounds and the Study of their application in C-H Functionalization Chemistry Restricted; Files Only

Lee,Maizie (Summer 2023)

Permanent URL: https://etd.library.emory.edu/concern/etds/9z903151c?locale=en
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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. 113C 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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