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Ruthenium-Catalyzed Dehydrogenative Amide Synthesis and Tungsten-Catalyzed C(sp3)–H Cyanation of Alkane : 루테늄 촉매에 의한 아마이드 결합의 탈수소화적 합성 및 텅스텐 촉매에 의한 알케인의 C(sp3)–H 시안화 반응

DC Field Value Language
dc.contributor.advisor최태림-
dc.contributor.author김건순-
dc.date.accessioned2022-04-20T07:51:18Z-
dc.date.available2022-04-20T07:51:18Z-
dc.date.issued2021-
dc.identifier.other000000167149-
dc.identifier.urihttps://hdl.handle.net/10371/178942-
dc.identifier.urihttps://dcollection.snu.ac.kr/common/orgView/000000167149ko_KR
dc.description학위논문(박사) -- 서울대학교대학원 : 자연과학대학 화학부, 2021.8. 최태림.-
dc.description.abstractRuthenium catalyzed base-free dehydrogenative amide synthesis from alcohol and amine and tungsten catalyzed highly efficient photocatalytic C(sp3)–H cyanation were developed. Part I describes dehydrogenative amide synthesis from alcohols and amines. Atom-economical amide synthesis is a continuous challenge in organic synthesis due to its high demand in biological chemistry and the pharmaceutical industry. Dehydrogenative coupling from alcohol and amine to amide is an attractive atom- and step-economical method. Previous developments of dehydrogenation reaction and dehydrogenative amide synthesis are discussed in chapter 1. Despite the significant advances of the dehydrogenative coupling of alcohol and amine, examples operating under the base-free catalytic conditions are relatively rare. A base-free dehydrogenative amide synthesis was achieved with N-heterocyclic carbene (NHC)-based ruthenium hydride catalysts (chapter 2). The developed method is operationally simple with readily available catalysts, which allows practical synthesis of amides.
Part II describes hydrogen atom transfer (HAT)-based C(sp3)–H functionalization reactions focusing on cyanations. Nitrile is a highly versatile functional group in organic synthesis because it has wide applications in polymer, pharmaceutical, battery industries. Furthermore, the nitrile group can easily be converted to various other functional groups including amide, carboxylic acid, amine, ketone, and heterocycle. Recent advances in photoredox catalysis enabled facile access to free radical species for the HAT reaction. The concept of applying HAT for organic synthesis and the reported examples of C–H functionalizations via HAT, especially using decatungstate, are discussed in chapter 3. The previously reported C(sp3)–H cyanations via HAT have limited scope with the drawback of using highly toxic metal cyanide or hydrogen cyanide. Highly efficient decatungstate-catalyzed C(sp3)–H cyanation is developed under mild conditions with tosyl cyanide (chapter 4). With the strong HAT ability of decatungstate catalyst, unactivated C(sp3)–H bond could be cyanated, demonstrating high functional group tolerance and remarkable efficiency even with ppm loading of catalyst.		-
dc.description.abstract루테늄 촉매를 이용한 알코올과 아민에서부터 아마이드를 염기가 없는 조건에서 탈수소화 반응을 통해 합성한 일과, 텅스텐 촉매를 사용하여 효율적인 C(sp3)–H 결합의 시안화 반응을 개발하였다. 논문의 첫 부분에서는 알코올과 아민으로부터 탈수소화를 통한 아마이드 합성법에 대해 기술하고자 한다. 아마이드는 생화학, 제약 등에서 많은 수요가 있어, 원자 경제적인 아마이드 합성이 지속적으로 요구되고 있다. 이러한 관점에서 수소만을 부산물로 내어놓는 알코올과 아민의 탈수소화를 통한 짝지음 반응은 큰 관심을 끌고있다. 1장에서는 이러한 탈수소화 반응 및 이를 이용한 유기합성에 관해서 다루게 될 것이다. 수많은 탈수소화를 통한 아마이드 합성 방법이 개발 됐지만 대부분은 강한 염기를 필요로 하였고, 이에 2장에서는 추가적인 염기가 없는 조건에서 탈수소화를 통한 아마이드 합성법의 개발에 대해 소개하고자 한다.
논문의 두번째 부분에서는 수소 원자 이동을 통한 C(sp3)–H 결합의 활성화를 통한 작용기화를 다루고자 한다. 특히, 다양한 산업에서 이용 될 뿐만 아니라, 유기합성에서 중요한 중간체인 나이트릴의 합성에 대해 논하고자 한다. 최근 광산화환원 촉매를 이용한 단전자 기작의 반응들이 활발하게 연구되고 있고, 수소 원자 이동에 대해서 더 쉬운 접근이 가능해졌다. 3장에서는 이러한 광산화환원 반응을 이용한 수소 원자 이동에 대해서 다루고자 한다. 특히, 저렴하면서도 직접적으로 수소 원자 이동 반응을 진행할 수 있는 텅스텐 산화물을 이용한 반응들에 대해 집중적으로 다루고자 한다. 4장에서는 텅스텐 촉매를 이용하여, 기존의 효율이 매우 낮았던 C(sp3)–H 결합의 시안화 반응의 효율을 크게 끌어올리는 반응 개발에 대해 소개하고자 한다.		-
dc.description.tableofcontentsPart I. Amides synthesis from C–N bond formation via catalytic dehydrogenation of alcohol 1
Chapter 1. Catalytic dehydrogenative amide synthesis from alcohols and amines 1
1.1 Introduction 1
1.2 C–H activation method: Dehydrogenation of aliphatic compounds 2
1.2.1 Oxidative dehydrogenation 2
1.2.2 Acceptorless dehydrogenation 7
1.3 Conventional amide synthesis 10
1.4 Amide synthesis via catalytic dehydrogenation of alcohol 11
1.5 Conclusion 16
1.6 References 17




Chapter 2. N-heterocyclic carbene-based well-defined ruthenium hydride complexes for direct amide synthesis from alcohols and amines under base-free conditions 22
2.1 Introduction 22
2.2 Results and discussion 24
2.2.1 Optimization of the reaction condition 24
2.2.2 Substrate scope evaluation 25
2.2.3 Mechanistic investigation 29
2.3 Conclusion 30
2.4 Experimental section 31
2.4.1 General information 31
2.4.2 General procedure for amide synthesis 31
2.4.3 Characterization of amide compounds 32
2.5 References 38

Part II. Aliphatic nitrile synthesis from direct C(sp3)–H bond cyanation 41
Chapter 3. Polyoxometalate catalysis hydrogen atom transfer based C(sp3)–H activation 41
3.1 Introduction 41
3.2 C–H activation method: Hydrogen atom transfer (HAT) 42
3.3 Polyoxometalate catalysis 49
3.3.1 Introduction and selected catalytic examples 49
3.3.2 Photocatalytic C(sp3)–H functionalization by decatungstate catalyst 51
3.4 Conclusion 56
3.5 References 57
Chapter 4. Direct C(sp3)–H Cyanation Enabled by Highly Active Decatungstate Photocatalyst 60
4.1 Introduction 61
4.2 Results and discussion 65
4.2.1 Optimization of the reaction condition 65
4.2.2 Simple organic molecules substrate scope evaluation 66
4.2.3 Complex molecules substrate scope evaluation 69
4.2.4 Evaluating catalyst efficiency 70
4.2.5 Mechanistic investigation 71
4.3 Conclusion 73
4.4 Experimental section 74
4.4.1 General information 74
4.4.2 UV-Vis spectra 76
4.4.3 Complementary Reaction Optimizaztion data 77
4.4.4 General Procedure for the C(sp3)–H Cyanation Reaction 82
4.4.5 Characterization of nitrile compounds 83
4.4.6 Mechanistic investigation 100
4.5 References 106

Appendix .
NMR Spectra .
Chapter 2 110
Chapter 4 119




List of Tables .
Chapter 2 ,
Table 2.1 Catalyst screening for amide synthesis 25
Table 2.2 Amide synthesis from amines and 2-phenylethanol 27
Table 2.3 Amide synthesis from 3-phenyl-1-propylamine and alcohols 28
Table 2.4 Transamidation of 4 with 1a 29

Chapter 4 .
Table 4.1 Optimization of the reaction conditions 65
Table 4.2 Reduction of catalyst loading 71
Table 4.3 Evaluation of catalytic conditions for C–H cyanation of cyclooctane 77
Table 4.4 Optimization of equivalences of cyclooctane 78
Table 4.5 Solvent screening 79
Table 4.6 Reduction of catalyst loading 81
Table 4.6 Quantum yield measurement 103


















List of Schemes .

Chapter 1 ,
Scheme 1.1 Dehydrogenation of aliphatic compounds 2
Scheme 1.2 Enzymatic dehydrogenation using metal oxo catalyst 2
Scheme 1.3 Oxidative dehydrogenation using oxygen as an oxidant 2
Scheme 1.4 The first transition metal-mediated dehydrogenation using TBE as an oxidant 3
Scheme 1.5 Transfer dehydrogenation of alcohol using a sacrificial hydrogen acceptor 4
Scheme 1.6 Transfer dehydrogenation of secondary amine to imine and primary amine to nitrile 5
Scheme 1.7 Palladium catalyzed transfer dehydrogenation of heterocycle 6
Scheme 1.8 AD of alkane with (PCP)IrHn complex 8
Scheme 1.9 Dehydrogenative alcohol activation 9
Scheme 1.10 Conventional amide bond formation using acyl halide or anhydride 10
Scheme 1.11 Early examples on catalytic dehydrogenative lactam formation 11
Scheme 1.12 The first intermolecular amide formation utilizing metal-ligand cooperation by aromatization-dearomatization 12
Scheme 1.13 Selected examples on AD amide synthesis utilizing metal-ligand cooperation 12
Scheme 1.14 Early examples on in situ ruthenium catalytic systems 14
Scheme 1.15 Exceptionally mild oxidative amide formation using Cu/nitroxyl catalyst 15
Scheme 1.16 Organophotocatalytic oxidative amide formation 15
Chapter 2 ,
Scheme 2.1 Proposed mechanism for acceptorless dehydrogenative amide synthesis starting from Ru chloride complex 23
Scheme 2.2 Proposed mechanism for dehydrogenative amidation via a direct pathway or via a base-catalyzed transamidation pathway through esters. 30

Chapter 3 ,
Scheme 3.1 Radical philicity and polarity match principle 43
Scheme 3.2 Category of photocatalytic HAT events 44
Scheme 3.3 Photocatalytic C(sp3)–H activation using aromatic ketones 45
Scheme 3.4 Eosin Y catalyzed C(sp3)–H functionalization under visible light irradiation 46
Scheme 3.5 Photocatalytic C(sp3)–H fluorination using metal oxide as photocatalysts 46
Scheme 3.6 Thiol organocatalyst for indirect HAT 47
Scheme 3.7 Persulfate mediated indirect HAT 48
Scheme 3.8 Aliphatic and aromatic compound oxidation catalyzed by POMs and green oxidant 50
Scheme 3.9 Changing selectivity by using POM-doped catalyst 51
Scheme 3.10 Decatungstate-catalyzed alkylation, vinylation, and carbonylation 51
Scheme 3.11 Rate-constant for hydrogen atom abstraction by excited decatungstate 52
Scheme 3.12 Site selectivity of TBADT-catalyzed C–H functionalization 52
Scheme 3.13 TBADT catalyzed α-iminoester or nitrile synthesis 53
Scheme 3.14 Aerobic oxidation using TBADT under batch and flow reaction 54
Scheme 3.15 TBADT and cobalt catalyzed dehydrogenation and alkenylation 55
Scheme 3.16 Metallaphotoredox catalyzed aryl and trifluoromethylation 55

Chapter 4 ,
Scheme 4.1 Direct C(sp3)–H cyanation 63
Scheme 4.2 Scope of substrates 68
Scheme 4.3 Cyanation of natural products and bioactive molecules 70
Scheme 4.4 Proposed reaction mechanism 73
Scheme 4.5 Optimization of cyanide sources 80
Scheme 4.6 Radical quenching experiment by adding TEMPO 100


List of Figures .

Chapter 2 ,
Figure 2.1 Well-defined Ru-NHC complexes 24

Chapter 4 ,
Figure 4.1 UV-Vis spectra of TBADT solution 10-4 M (black line), tosyl cyanide solution 5×10-2 M (red line), cyclooctane solution 4×10-1 M (blue line) in acetonitrile/water (19:1 (v/v)). 76
Figure 4.2 Selective ion chromatogram of the crude mixture showing ions of mass 238.90–239.90 100
Figure 4.3 Mass spectrum of peak eluted at 11.4 min 101
Figure 4.4 Absorbance of the Ferrioxalate Solutions 102
Figure 4.5 Absorbance of 10-4 M TBADT in CH3CN/H2O (19:1 (v/v)) 103
Figure 4.6 Kinetic isotope effect measurement with 2b and 2b-D12 105		-
dc.format.extentx, 162-
dc.language.isoeng-
dc.publisher서울대학교 대학원-
dc.subjectMethodology-
dc.subjectOrganic synthesis-
dc.subjectOrganometallic catalysis-
dc.subjectPhotocatalysis-
dc.subjectC(sp3 )– H 활성화-
dc.subject탈수소화-
dc.subject루테늄-
dc.subject알코올-
dc.subject아민-
dc.subject아마이드-
dc.subject광촉매-
dc.subject수소 원자 이동-
dc.subject텅스텐-
dc.subject나이트릴-
dc.subject.ddc540-
dc.titleRuthenium-Catalyzed Dehydrogenative Amide Synthesis and Tungsten-Catalyzed C(sp3)–H Cyanation of Alkane-
dc.title.alternative루테늄 촉매에 의한 아마이드 결합의 탈수소화적 합성 및 텅스텐 촉매에 의한 알케인의 C(sp3)–H 시안화 반응-
dc.typeThesis-
dc.typeDissertation-
dc.contributor.AlternativeAuthorKunsoon Kim-
dc.contributor.department자연과학대학 화학부-
dc.description.degree박사-
dc.date.awarded2021-08-
dc.identifier.uciI804:11032-000000167149-
dc.identifier.holdings000000000046▲000000000053▲000000167149▲-
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