Development of Biaryl N-Heterocyclic Carbene Ligands Featuring Non-Covalent Interactions
- Abstract
- The field of organotransition-metal chemistry has extensively studied the development of novel and efficient catalysts for homogeneous catalysis. N-Heterocyclic carbenes (NHCs) are a powerful class of ligands in transition metal catalysis due to their strong electron-donating ability and excellent synthetic flexibility. They have been recognized as such since the stable free carbene was isolated by Arduengo in 1991. Various structural modifications have been employed to adjust the electronic and steric characteristics of NHC ligands, based on the prototypical imidazolylidene skeleton. Imidazo[1,5- a]pyridin-3-ylidene (ImPy) ligands have a rigid bicyclic structure comprising a C5-positioned aryl group. Aryl substituents of the bicyclic ImPy are positioned near a metal coordination sphere, thus allowing for bonding interactions of the metal with substituent. Additionally, ImPy ligands can be synthesized via a concise synthetic route, enabling the convenient incorporation of numerous functional substituents. In line with our interest to developing advanced NHC-based catalysts, we suggest a variety of ligands that feature non-covalent interactions. The present thesis describes the development of imidazopyridine-based NHC transition metal complexes and their application to chemical reactions: diastereoselective addition and desymmetric C-N bond formation. In catalyst design, the Cu-F interaction play a crucial role in stabilizing catalyst and reaction intermediate, thereby influencing the reactivity of catalytic processes. Additionally, fluorine atom, which is not impose spatial demands, can fundamentally alter the performance of the catalyst. The fluorinated aryl groups on the ligand structures also improve the π-back-donation from the metal. Chapter 2 describes the synthesis of fluorinated ImPy ligand (F-ImPy), characterized by a Cu-F interaction and a C5-aryl substituent and their application in the diastereoselective additions of 1,3- PhD/CH 20182101
- Issued Date
- 2025
- Type
- Thesis
- Alternative Author(s)
- Woosong Han
- Department
- 대학원 화학과
- Advisor
- Hong, Sukwon
- Table Of Contents
- The field of organotransition-metal chemistry has extensively studied the development of novel and efficient catalysts for homogeneous catalysis. N-Heterocyclic carbenes (NHCs) are a powerful class of ligands in transition metal catalysis due to their strong electron-donating ability and excellent synthetic flexibility. They have been recognized as such since the stable free carbene was isolated by Arduengo in 1991. Various structural modifications have been employed to adjust the electronic and steric characteristics of NHC ligands, based on the prototypical imidazolylidene skeleton. Imidazo[1,5-a]pyridin-3-ylidene (ImPy) ligands have a rigid bicyclic structure comprising a C5-positioned aryl group. Aryl substituents of the bicyclic ImPy are positioned near a metal coordination sphere, thus allowing for bonding interactions of the metal with substituent. Additionally, ImPy ligands can be synthesized via a concise synthetic route, enabling the convenient incorporation of numerous functional substituents. In line with our interest to developing advanced NHC-based catalysts, we suggest a variety of ligands that feature non-covalent interactions. The present thesis describes the development of imidazopyridine-based NHC transition metal complexes and their application to chemical reactions: diastereoselective addition and desymmetric C-N bond formation.
In catalyst design, the Cu-F interaction play a crucial role in stabilizing catalyst and reaction intermediate, thereby influencing the reactivity of catalytic processes. Additionally, fluorine atom, which is not impose spatial demands, can fundamentally alter the performance of the catalyst. The fluorinated aryl groups on the ligand structures also improve the π-back-donation from the metal. Chapter 2 describes the synthesis of fluorinated ImPy ligand (F-ImPy), characterized by a Cu-F interaction and a C5-aryl substituent and their application in the diastereoselective additions of 1,3-enyne nucleophile to ketones. X-ray and non-covalent interaction (NCI) analysis elucidated both the Cu-arene interaction and the Cu-F interaction in the catalyst. These biaryl ImPy−Cu catalysts were effectively employed in the Cu-catalyzed diastereoselective addition reaction of easily accessible olefins to ketones. F-ImPy-Cu catalyst exhibits higher reactivity than non-fluorinated ImPy-Cu catalysts. Consequently, we achieved tertiary alcohol synthesis with up to 96% yield and up to >10:1 diastereoselectivity.
Anagostic interactions play a crucial role in stabilizing specific ligand and intermediate conformations, thereby influencing the reactivity and selectivity of catalytic processes. In chiral catalyst design, anagostic C-H···M interactions are particularly intriguing as they can restrict the rotation of substituents around the metal center. This restriction is crucial for forming a well-defined chiral environment, essential for achieving high enantioselectivity in catalytic reactions. Notably, this study represents the first attempt to utilize anagostic C-H···M interactions to control enantioselectivity, underscoring its innovative approach. Chapter 3 describes novel chiral biaryl ImPy ligands, characterized by an anagostic C-H···Pd interaction and a C5-aryl substituent and their application as steering ligands in Pd-catalyzed desymmetric C-N bond formation of 3,4-dihydroquinolin-2-ones with quaternary stereocenters. X-ray and NCI analysis elucidated both the Pd-arene interaction and the anagostic interaction in the chiral catalyst. These biaryl ImPy−Pd catalysts were effectively employed in the Pd-catalyzed asymmetric desymmetric C-N cross-coupling of malonamide derivatives. Consequently, we achieved the synthesis of chiral 3,4-dihydroquinolin-2-one derivatives with excellent yields (up to 99%) and high enantioselectivities (up to 97:3 er).
TABLE OF CONTENTS
ABSTRACT···················································································································i
TABLE OF CONTENTS·······························································································iii
LIST OF FIGURES·····································································································vii
LIST OF SCHEMES·····································································································ix
LIST OF TABLES········································································································xi
CHAPTER 1. A Thesis Overview····················································································1
1.1 Non-covalent Interactions in Metal Complex Catalysis··················································2
1.1.1 Intermolecular Non-Covalent Interactions···························································4
1.1.2 Intramolecular Non-Covalent Interactions···························································6
1.2 N-Heterocyclic Carbenes (NHCs)···············································································7
1.3 Imidazo[1,5-a]pyridin-3-ylidene···············································································11
1.3.1 Achiral Imidazo[1,5-a]pyridin-3-ylidene Ligands···············································12
1.3.2 Chiral Imidazo[1,5-a]pyridin-3-ylidene Ligands·················································14
1.3.2.1 Chiral Monodentate Imidazo[1,5-a]pyridin-3-ylidene Ligands·····················15
1.3.2.2 Chiral bidentate Imidazo[1,5-a]pyridin-3-ylidene Ligands···························22
1.4 Thesis Research······································································································27
1.5 References··············································································································28
CHAPTER 2. Fluorinated Biaryl N-Heterocyclic Carbene Ligand with Non-Covalent Interaction for Cu-catalyzed Diastereoselective Addition Reaction································39
2.1 Introduction·············································································································40
2.2 Results and Discussion······························································································42
2.2.1 Synthesis of Ligands and Catalysts····································································42
2.2.2 X-ray Crystallography······················································································43
2.2.3 Non-Covalent Interaction Plot Analysis······························································44
2.2.4 Electronic Properties for F-ImPy Ligands by IR and 77Se-NMR····························45
2.2.5 Catalytic Properties of ImPy-Cu Complexes·······················································47
2.3 Conclusion··············································································································52
2.4 Experimental Section·······························································································53
2.4.1 General Information·························································································53
2.4.2 General Procedure for Synthesis of ImPy Ligands and Catalysts····························54
2.4.3 General Procedures for Diastereoselective Addition with 1,3-Enyne and Ketones···60
2.4.4 X-ray Analysis for Complex 4e·········································································63
2.4.5 Computational Study and Non-Covalent Interaction Plot Analysis························65
2.5 References···············································································································69
APPENDIX 1: NMR Spectra of Compounds Relevant to Chapter 2·······························75
CHAPTER 3. Chiral Biaryl N-Heterocyclic Carbene-Palladium Catalysts with Anagostic C-H∙∙∙Pd Interaction for Enantioselective Desymmetric C-N Cross-Coupling···············100
3.1 Introduction············································································································101
3.2 Results and Discussion····························································································105
3.2.1 Synthesis of Ligands and Catalysts···································································105
3.2.2 Catalytic Properties of ImPy-Pd Complexes······················································106
3.2.3 X-ray Crystallography····················································································110
3.2.4 Non-Covalent Interaction Plot Analysis····························································111
3.2.5 Electronic Properties for F-ImPy Ligands by IR and 77Se-NMR···························112
3.3 Conclusion·············································································································114
3.4 Experimental Section······························································································115
3.4.1 General Information·······················································································115
3.4.2 Synthesis of Ligands and Catalysts···································································116
3.4.2.1 Preparation of Chiral Amines··································································116
3.4.2.2 Preparation of Chiral Imidazo[1,5-a]pyridinium Salts································122
3.4.2.3 Preparation of ImPy-Metal Complexes and ImPy-Se Adducts·····················131
3.4.3 Substrate Synthesis and Compound Characterization·········································137
3.4.4 General Procedures for Desymmetric C-N Bond Formation································147
3.4.5 X-ray Crystallography Data for 3f and L8-Pd(allyl)Cl·······································163
3.4.6 Non-Covalent Interaction Plot Analysis····························································176
3.5 References·············································································································181
APPENDIX 2: NMR Spectra of Compounds Relevant to Chapter 3······························190
APPENDIX 3: The Cartesian Coordinates (Å) for the L8-Pd Complex as a Function of the Dihedral Angle Pd-C1-C7-H1················································································255
CURRICULUM VITAE·····························································································276
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- Appears in Collections:
- Department of Chemistry > 4. Theses(Ph.D)
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