Exploring the Influence of Dirhodium Catalyst Structure on the Regio- and Stereoselectivity Properties of Donor/Acceptor Carbenes Open Access
Wertz, Benjamin (Summer 2020)
Abstract
The reactions of donor/acceptor dirhodium carbenes with the C-H bonds of organic compounds are capable of very high regio- and stereoselectivity and have the ability to select preferentially for highly specific C-H bonds in substrate molecules that may contain many of them. Over the past decade, the discovery of novel dirhodium catalysts with a variety of shapes and selectivity profiles has led to many remarkable advances in the field of organic synthesis. These have caused chemists to reevaluate the conventional thinking that non-acidic C-H bonds at sp3-hybridized positions are inert and do not represent viable positions for synthetic manipulation.
The first chapter of this thesis presents the development of these novel catalysts in historical context and highlights some of the reactions that they can perform. While there are undoubtedly many other valuable applications for the catalysts described in this section, the work has been presented as a reference for future researchers who may be searching for a simple set of guidelines to better understand how they can apply dirhodium carbene chemistry effectively in their research. Accordingly, the types of reactions described in this chapter are diverse and are intended to call attention to both the strengths and weaknesses of dirhodium carbene strategies for organic synthesis.
The second chapter contains original research which highlights the relationship between the ligand structure and the selectivity properties of the dirhodium cyclopropanecarboxylate complexes. Catalysts of this type are well established for the regio- and stereoselective functionalization of sterically accessible primary or secondary C-H sites. For trisubstituted cyclopropanes, substitution at the C1 aryl group controls the regio- and stereoselectivity of the catalysts. This work reveals how the formal removal of an aryl substituent at the C2-position of the cyclopropane can also significantly impact the shape of the catalysts and the selectivity observed in their reactions.
Section 3 presents a novel contribution to synthetic organic reaction methodology: the application of dirhodium tetracarboxylate catalysts to the functionalization of aryl- or heteroaryl- cyclobutanes. Depending on the catalyst chosen, either the benzylic C1-position of the arylcyclobutane or the distal C3 methylene group reacts with high regio- and stereoselectivity.
The fourth chapter of this work describes the design, synthesis, and applications of dirhodium cyclopropanecarboxylate catalysts with two aryl groups and one other substituent bonded to the cyclopropane. A series of cyclohexyl- and trimethylsilyl- substituted diarylcyclopropane carboxylate complexes were prepared and tested in C-H insertion and asymmetric cyclopropanation reactions. The shapes and selectivity properties of the new catalysts mirrored their triarylcyclopropane counterparts, but with some subtle differences. A trimethylsilyl- substituted catalyst was proficient for asymmetric cyclopropanations at very low loading.
Table of Contents
Chapter 1. General Introduction to Donor/Acceptor Carbenes and Dirhodium Catalysts 1
1.1 Introduction 1
1.2 Structure of Dirhodium Tetracarboxylates 3
1.3 Mechanism of Dirhodium Carbene Reactions 6
1.4 Strengths and Limitations of Donor/Acceptor Carbenes 13
1.5 Stereoselective Cyclopropanation Reactions 18
1.6 Established Classes of Dirhodium Tetracarboxylate Catalyst 23
1.6.1 Development and Applications of Dirhodium Tetraprolinate Catalysts 25
1.6.2 Dirhodium Complexes with Phthalimido- Protected Amino Acid Ligands 29
1.6.3 Introduction to Dirhodium Triarylcyclopropanecarboxylates 36
1.7 C-H Functionalization with Dirhodium Carbenes 42
1.7.1 Reactions at Innately Favored Sites 43
1.7.2 Site- and Stereoselective Functionalization of Unactivated C-H Bonds 47
1.8 References 62
Chapter 2. Study of Dirhodium Diarylcyclopropanecarboxylate Catalysts 71
2.1 Background 71
2.1.1 Substituent Effects in The Triarylcyclopropanecarboxylates 72
2.1.2 Design of Dirhodium Diarylcyclopropanecarboxylates 75
2.2 Results and Discussion 77
2.2.1 Synthesis of Diarylcyclopropanecarboxylates 79
2.2.2 Evaluation of Catalysts 87
2.2.3 X-Ray Analysis of Dirhodium Catalysts 91
2.2.4 DFT Study of Rh2(DPCP)4 Catalysts 94
2.2.5 Conclusion 98
2.3 References 100
Chapter 3. The Regio- and Stereoselective Functionalization of Arylcyclobutanes 103
3.1 Introduction and Related Work 103
3.1.1 Selective Functionalization of Silacyclobutanes and Silacyclopentanes 105
3.1.2 Selective Functionalization of Cyclohexanes 107
3.1.3 Selective Functionalization of Bicyclo[1.1.1]pentanes 110
3.1.4 Overcoming Electronic Activation with ortho-TPCP Catalysts 113
3.2 Results and Discussion 115
3.2.1 Synthesis of Cyclobutane Substrates 119
3.2.2 C-H Functionalization of Arylcyclobutanes at C1 121
3.2.3 C-H Functionalization of Arylcyclobutanes at C3 124
3.2.4 Discovery and Isolation of Stable Pyridinium Ylide Dyes 127
3.3 Conclusion 131
3.4 References 132
Chapter 4. Rh2(DPCP)4 Catalysts With sp3-Hybridied Substituent Groups 136
4.1 Introduction 136
4.1.1 Design of sp3-Functionalized Diarylcyclopropanecarboxylate Catalysts 138
4.2 Results and Discussion 140
4.2.1 Preparation of Cyclohexyl-DPCP Catalysts 140
4.2.2 Evaluation of Cyclohexyl-DPCP Catalysts 144
4.2.3 Trimethylsilyl Diarylcyclopropanecarboxylates 147
4.2.4 Evaluation of TMS-DPCP Catalysts 151
4.2.5 C-H Insertion Reactions with Rh2(2-TMS-DPCP)4 Catalysts 154
4.2.6 Cyclopropanation Using the Rh2(2-TMS-DPCP)4 Catalysts 156
4.2.7 Structure of the Trimethylsilyl-DPCP Catalysts 159
4.3 Conclusion 165
4.4 References 166
Experimental Sections 168
S.1 General Methods 168
S.2 Experimental Section for Chapter 2 169
S.2.1 List of Previously Reported Compounds 169
S.2.2 Synthesis of Cyclopropanecarboxylate Ligands 171
S.2.3 Preparation of Dirhodium Catalysts 182
S.2.4 Evaluation of Dirhodium Catalysts, General Procedures 190
S.2.5 Characterization Data for Primary Alcohol Derivatives 193
S.2.6 Determination of the Relative Configuration for Compounds 2.41 and 2.42 199
S.2.7 1H and 13C NMR Spectra 200
S.2.8 Chiral HPLC Traces 223
S.2.9 Computational Studies 252
S.3.10 References 284
S.3 Experimental Section for Chapter 3 285
S.3.1 General Considerations 285
S.3.2 Catalyst Structures 286
S.3.3 Synthesis of Substrates and Reagents 287
S.3.4 Catalyst Screening for C-H Functionalization Reactions 294
S.3.5 Characterization of C1 Functionalization Products 304
S.3.6 Characterization of C3 Functionalization Products 316
S.3.7 Competition Study 328
S.3.8 Determination of Absolute Configurations 333
S.3.9 Synthesis and Characterization of Stable Pyridinium Ylides 334
S.3.10 NMR Spectra 336
S.3.11 Chiral HPLC Traces 369
S.3.12 References 395
S.4 Experimental Section for Chapter 4 397
S.4.1 General Methods 397
S.4.2 List of Previously Prepared Compounds 398
S.4.3 Synthesis of Cyclopropanecarboxylate Ligands 399
S.4.4 Preparation and Characterization of Dirhodium Catalysts 417
S.4.5 Reactions with Other Substrates 423
S.4.6 Copies of NMR Spectra 430
S.4.7 Chiral HPLC Traces 456
S.4.8 Computational Studies 494
S.4.9 References 539
Appendix: X-Ray Crystallography Section 540
A.1 Single Crystal X-Ray Crystallographic Data and Experimental 540
A.2 References 739
About this Dissertation
| School | |
|---|---|
| Department | |
| Degree | |
| Submission | |
| Language |
|
| Research Field | |
| Keyword | |
| Committee Chair / Thesis Advisor | |
| Committee Members |
Primary PDF
| Thumbnail | Title | Date Uploaded | Actions |
|---|---|---|---|
|
|
Exploring the Influence of Dirhodium Catalyst Structure on the Regio- and Stereoselectivity Properties of Donor/Acceptor Carbenes () | 2020-07-08 20:06:19 -0400 |
|
Supplemental Files
| Thumbnail | Title | Date Uploaded | Actions |
|---|