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Development of Catalytic Transformations of Isocyanides and Allylic Compounds : 아이소사이아나이드와 알릴 화합물의 촉매적 변환 개발

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dc.contributor.advisor이홍근-
dc.contributor.author김정원-
dc.date.accessioned2020-10-13T04:06:06Z-
dc.date.available2020-10-13T04:06:06Z-
dc.date.issued2020-
dc.identifier.other000000161168-
dc.identifier.urihttps://hdl.handle.net/10371/170785-
dc.identifier.urihttp://dcollection.snu.ac.kr/common/orgView/000000161168ko_KR
dc.description학위논문 (박사) -- 서울대학교 대학원 : 자연과학대학 화학부, 2020. 8. 이홍근.-
dc.description.abstractCatalytic transformations of the organic compounds provide useful strategies to produce valuable structures efficiently. The control of catalytic conditions, based on the chemical property of the substrate and the previously established strategies, is the key to achieving the unprecedented and novel organic transformations. This thesis covers the discovery of an array of catalytic transformations of isocyanides and allylic compounds toward the synthetically meaningful chemical structures.
In Part 1, the chemistry and the catalytic utilization of isocyanides will be discussed. The ability of the terminal carbon of the isocyanide as both a nucleophile and an electrophile has enabled the various types of activation modes in the catalysis. Chapter 1 describes the detailed mechanistic strategies for the activation of the terminal carbon of isocyanides, together with the representative examples reported so far. Chapters 2 and 3 introduce a new approach for the catalytic nucleophilic activation of the isocyanides. Especially, the utilization of N-heterocyclic carbene (NHC) as an organocatalyst for the transformations of isocyanides will be demonstrated. The reactions with ketones provide several types of enaminones in high efficiency (Chapter 2), and the novel formamidine structure is accessible through the reaction between indoles and isocyanides using the developed activation strategy (Chapter 3).
Part 2 discusses the achievement of the catalytic C(sp3)–H bond functionalizations via visible light photoredox catalysis. The use of visible light as an energy source to conduct a challenging C(sp3)–H bond activation reaction has been widely investigated in the organic synthesis. Chapter 4 reviews the currently established approaches for the C(sp3)–H bond functionalizations with visible light photoredox catalysis, based on the categorized strategies and the representative transformations. Chapter 5 discloses a new method to synthesize allyl thioethers from simple allylic compounds and disulfides via visible light photoredox catalysis. The design of the target catalytic cycle for the prevention of the side reaction (hydrothiolation) enabled the selective allylic C(sp3)–H bond thiolation, and the in-depth mechanistic studies expanded the substrate scope through the introduction of tailored unsymmetrical disulfides.
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dc.description.abstract유기 화합물의 촉매적 변환은 가치가 높은 구조를 합성할 수 있는 유용한 전략이다. 기질의 화학적 특성과 이전에 구축되어 온 전략들을 기반으로 촉매 조건을 구성하여, 새롭고 독창적인 유기 변환들을 개발할 수 있다. 본 논문에서는 아이소사이아나이드와 알릴 화합물의 새로운 촉매적 변환의 개발을 통해 합성적으로 유용한 화학 구조를 얻기 위한 과정에 대해 논의한다.
논문의 첫 부분에서는 아이소사이아나이드의 화학적 특성과 촉매적 활용에 대해 논의한다. 친핵체와 친전자체 양쪽의 성질을 모두 가지는 아이소사이아나이드의 말단 탄소는 촉매적 변환에서 다양한 방식으로 활성화될 수 있다. 제1장에서는 아이소사이아나이드의 말단 탄소의 활성화를 유도하는 자세한 기작들을 대표적인 예시 반응들과 함께 소개한다. 제2장과 제3장에서는 아이소사이아나이드의 촉매적 친핵체 활성화를 위한 새로운 접근법을 소개한다. 특히, 질소고리화카벤 (NHC)을 유기촉매로 활용하여 아이소사이아나이드의 새로운 변환 방식들을 제시한다. 케톤과의 반응을 통해 다양한 종류의 엔아민온을 높은 수율로 합성할 수 있으며 (2장), 인돌과 아이소사이나이드 사이의 반응을 통해 독특한 구조의 폼아미딘을 합성할 수 있었다 (3장).
논문의 두 번째 부분에서는 가시광 광산화환원 촉매 체계에서 sp3 혼성 탄소-수소 결합의 작용기화를 논한다. 가시광선을 에너지원으로 도전적인 탄소-수소 결합을 활성화하는 전략은 유기 합성에서 널리 연구되고 있다. 제4장 에서는 sp3 혼성 탄소-수소 결합 작용기화 반응을 위해 현재까지 개발된 가시광 광산화환원 촉매 체계를 전략별로 구분하여 대표적인 예시들과 함께 소개한다. 제5장 에서는 가시광 광산화환원 촉매 체계를 활용하여 간단한 알릴 화합물과 다이설파이드로부터 알릴 티오에터를 합성하는 새로운 방법론을 제시한다. 예상되는 부반응 (하이드로티올레이션)을 억제하는 촉매 순환을 구성하여 알릴 자리 탄소-수소 티오화 반응을 선택적으로 진행하였고, 깊이 있는 반응 기작 연구로부터 제시된 비대칭형 다이설파이드를 도입하여 반응 기질의 폭을 넓힐 수 있었다.
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dc.description.tableofcontentsPart 1. Catalytic Transformations of Isocyanides 1
Chapter 1. Utilization of Isocyanides in Organic Transformations 1
1.1 Introduction 1
1.2 Activation of the isocyanides with electrophilic component 2
1.2.1 Passerini and Ugi multicomponent reaction (MCR) 2
1.2.2 Activation of isocyanides by other electrophilic partners 5
1.2.3 Activation of isocyanides by transition-metal catalysts 12
1.3 Activation of the isocyanides with nucleophilic component 21
1.3.1 Intermolecular reactions 21
1.3.2 Intramolecular reactions 23
1.4 Activation of the isocyanides with radical components 26
1.4.1 Radical cyclization 26
1.4.2 Intermolecular radical coupling. 30
1.4.3 Reactions initiated by visible light photoredox catalysis 32
1.5 Other utilization strategies 34
1.5.1 Activation of α-proton of isocyanides 34
1.5.2 Reactions with carbenoid species 35
1.6 Summary and outlook 37
1.7 References 38
Chapter 2. Organocatalytic Activation of Isocyanides: N-Heterocyclic Carbene-Catalyzed Enaminone Synthesis from Ketones 46
2.1 Introduction 46
2.2 Result and discussion 50
2.2.1 Optimization 50
2.2.2 Substrate scope evaluation 52
2.2.3 Mechanistic investigation 58
2.3 Conclusion 61
2.4 Experimental section 62
2.4.1 General information 62
2.4.2 Initial experiment of (Z)-enaminone synthesis 63
2.4.3 General procedure for the synthesis of enaminone (3) 63
2.4.4 Optimization tables . 64
2.4.5 Experimental procedures for the control experiments 68
2.4.6 Experimental procedures for the gram-scale reaction 71
2.4.7 Crystallographic data of 3sa 72
2.4.8 Spectroscopic data. 74
2.5 References 88
Chapter 3. Dual Activation of Nucleophiles and Electrophiles by NHeterocyclic Carbene Organocatalysis: Chemoselective NImination of Indoles with Isocyanides 92
3.1 Introduction 92
3.2 Result and discussion 95
3.2.1 Optimization 95
3.2.2 Substrate scope evaluation 97
3.2.3 Mechanistic investigation 100
3.3 Conclusion 105
3.4 Experimental section 106
3.4.1 General information 106
3.4.2 Initial experiment of formamidine 4aa synthesis 107
3.4.3 Characterization of formamidine 4aa 108
3.4.3.1 Crystallographic data 108
3.4.3.2 2D-ROESY spectra 110
3.4.4 Optimization tables 112
3.4.5 Experimental procedure for the synthesis of 4aa via indole anion. 115
3.4.6 Experimental procedures for the control experiments. 116
3.4.7 Experimental procedures for deuterium incorporation experiments 118
3.4.8 Experimental procedures for trials for the detection of formimidate intermediate 121
3.4.9 General procedures for the synthesis of new compounds and characterization data 123
3.4.9.1 Synthetic procedures and characterization of new isocyanides 123
3.4.9.2 Synthetic procedures and characterization of formamidines (4) 125
3.5 References 141
Part 2. Catalytic C(sp3)H Bond Functionalizations of Allylic Compounds 144
Chapter 4. C(sp3)H Bond Functionalizations via Visible Light Photoredox Catalysis 144
4.1 Introduction 144
4.2 C(sp3)H bond activation via single-electron transfer (SET) 146
4.2.1 SET of amines . 147
4.2.2 SET of π-systems 158
4.2.3 SET of conjugated heteroatoms 160
4.3 C(sp3)H bond activation via hydrogen atom transfer (HAT) 161
4.3.1 HAT with oxygen-centered radicals 163
4.3.2 HAT with nitrogen-centered radicals. 175
4.3.3 HAT with sulfur-centered radicals 183
4.3.4 HAT with halogen-centered radicals 185
4.3.5 HAT with carbon-centered radicals. 191
4.4 C(sp3)H bond activation via proton-coupled electron transfer (PCET) 193
4.5 Summary and outlook 195
4.6 References 196
Chapter 5. Direct Allylic C(sp3)H Thiolation with Disulfides via Visible Light Photoredox Catalysis 207
5.1 Introduction 207
5.2 Result and discussion 210
5.2.1 Optimization 210
5.2.2 Substrate scope evaluation 212
5.2.3 Further utilization of allyl thioethers 215
5.2.4 Mechanistic investigations 217
5.2.5 Expansion of the substrate scope toward alkyl allyl sulfides 227
5.3 Conclusion 233
5.4 Experimental section 234
5.4.1 General information 234
5.4.2 Substrate preparation. 236
5.4.3 Screening experiments 244
5.4.4 Sensitivity assessment of the reaction. 247
5.4.5 General procedure for the synthesis of allyl thioethers (3) 249
5.4.5.1 Synthesis of allyl thioethers from symmetric disulfides 249
5.4.5.2 Synthesis of allyl thioethers from unsymmetrical disulfides 250
5.4.5.3 Scaled-up reaction for the synthesis of allyl thioether 3aa 251
5.4.6 Characterization of allyl thioethers (3) 252
5.4.7 Post modifications of allyl thioethers 267
5.4.7.1 Synthesis of allyl sulfoxide (3ahsulfoxide) 267
5.4.7.2 Synthesis of allyl sulfone (3oasulfone) 268
5.4.7.3 Interrupted Pummerer coupling/[3,3]-sigmatropic rearrangement with N-methylindole 269
5.4.7.4 Doyle-Kirmse reaction with allyl thioether 3aa 270
5.4.7.5 Modified Julia olefination with hydrocinnamaldehyde 271
5.4.8 General procedures for single-electron oxidant additive studies 272
5.4.9 DFT calculation 274
5.4.9.1 DFT calculation of redox potentials 274
5.4.9.1.1 The redox potential of 2a-rad 275
5.4.9.1.2 The redox potential of 2h-rad 276
5.4.9.1.3 The redox potential of 3ah-rad 277
5.4.9.2 DFT calculation of the reaction pathway 278
5.4.10 Stern-Volmer quenching experiment 280
5.4.11 Quantum yield measurement 283
5.4.11.1 Actinometry. 283
5.4.11.2 Absorption spectrum of Ir(CF3ppy)3 in DMA/olefin 2a 285
5.4.11.3 Quantum yield measurement 286
5.4.12 Kinetic isotope effect 287
5.4.13 CV experiments 289
5.4.13.1 Calibration of the reference electrode 289
5.4.13.2 Disulfide 1q. 290
5.4.13.3 Disulfide 1qBzt. 291
5.4.13.4 Disulfide 1qClBzt 292
5.4.13.5 Disulfide 1qNO2Ph 293
5.5 References 294
Appendix 302
NMR Spectra 302
Chapter 2 302
Chapter 3 338
Chapter 5 365
Cartesian Coordinates for DFT Calculation 429
Chapter 5 429
Acknowledgement 436
Abstract in Koreans 440
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dc.language.isoeng-
dc.publisher서울대학교 대학원-
dc.subjectIsocyanide-
dc.subjectnucleophilic activation-
dc.subjectorganocatalysis-
dc.subjectN-heterocyclic carbene-
dc.subjectallylic compound-
dc.subjectvisible light-
dc.subjectphotoredox catalysis-
dc.subjectallyl thioether-
dc.subject아이소사이아나이드-
dc.subject친핵성 활성화-
dc.subject유기촉매-
dc.subject질소고리화카벤-
dc.subject알릴 화합물-
dc.subject가시광선-
dc.subject광산화환원 촉매반응-
dc.subject알릴 티오에터-
dc.subject.ddc540-
dc.titleDevelopment of Catalytic Transformations of Isocyanides and Allylic Compounds-
dc.title.alternative아이소사이아나이드와 알릴 화합물의 촉매적 변환 개발-
dc.typeThesis-
dc.typeDissertation-
dc.contributor.department자연과학대학 화학부-
dc.description.degreeDoctor-
dc.date.awarded2020-08-
dc.contributor.major유기화학-
dc.identifier.uciI804:11032-000000161168-
dc.identifier.holdings000000000043▲000000000048▲000000161168▲-
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