학위논문 (박사)-- 서울대학교 대학원 : 자연과학대학 화학부, 2019. 2. 이철범.본 학위 논문에는 로듐 촉매에 의한 비대칭 고리화 반응의 개발에 대한 연구 결과가 수록되어 있다. 고리화 반응을 위한 전 이금속-바이닐리딘 매개 촉매 반응의 활용 가능성을 확장시키기 위하여(제 1 장), 말단 알카인에 연결된 엔아민에서 일어나는 로듐 촉매 알켄화 반응에 대한 연구를 수행하였다(제 2 장). 로듐-바이 닐리딘 착물을 촉매 중간체로 활용하여 알카인-엔아민의 고리화 반응을 수행하고, 궁극적으로 카이랄 엔아민을 사용한 부분 입체 선택적 탄소-탄소 결합 형성 반응을 통해 카이랄 사차 탄소를 지 닌 사이클로펜텐 합성법을 제안한다.
본 논문의 후반부는 로듐 촉매와 유기붕소산에 의한 알카 인의 이웃 자리 탄소기능화 반응의 연구 결과를 다루고 있다(제 3 장). 알카인-이민의 로듐 촉매 연쇄 첨가-고리화 반응에서는 단일 로듐 촉매가 순차적인 분자간, 분자내 1,2-탄소로듐화 반응을 매개 하여 알킬리덴-사이클로뷰틸아민의 합성을 가능토록 한다(제 4 장). 또한 로듐 촉매에 배위할 수 있는 카이랄 리간드에 의한 거울상 선택적 반응을 통해 높은 광학 활성을 갖는 사이클로뷰틸아민의 합성법을 보인다. 앞서 확인한 알켄-로듐 중간체의 탄소-질소 이중 결합 첨가 반응성을 바탕으로 알카인-하이드라존의 로듐 촉매 연 쇄 첨가-고리화-재배열 반응을 개발하였다(제 5 장). 본 연구에서는 로듐-촉매 연쇄 고리화 반응과 레트로-엔 반응의 융합을 통해 무흔적 사이클로알켄 합성을 수행하고, 반응 중간체를 분석하여 반응 메커니즘을 규명한다. 로듐-카이랄 리간드 착물은 알켄-로듐 중간 체의 비대칭 탄소-질소 이중 결합 첨가 반응을 유도하고, 결과적으 로 분자 밖 입체 중심을 지닌 사이클로펜틴을 높은 거울상 순도로 합성한다.Described here is the development of rhodium-catalyzed asymmetric cyclization reactions of alkynes. For the amplification of synthetic utilities of transition metal vinylidene mediated catalysis in carbocyclization reactions (Chapter 1), a rhodium-catalyzed intramolecular alkenylation of enamines tethered with terminal alkyne was developed (Chapter 2). By using a rhodium-vinylidene complex as a catalytic intermediate, 5-endo-dig Conia- ene type process could be achieved with alkynylenamine substrates. Furthermore, chiral enamines derived from chiral primary amines could induce diastereoselectivity in the C‒C bond formation, giving rise to cyclopentenes that have a chiral quaternary carbon.
In contrast to the works described above for the anti-Markovnikov carbofunctionalization of terminal alkynes, following studies focused on a rhodium-catalyzed vicinal carbofunctionalization of alkynes with organoboron compounds (Chapter 3). In a rhodium-catalyzed tandem addition‒cyclization of alkynylimines, a single rhodium catalyst mediated a sequential inter- and intramolecular 1,2-carborhodations, providing alkylidene cyclobutylamines (Chapter 4). We have shown that hydrolysis- prone aliphatic sulfonylimines could participate in a tandem process, and the exploration of chiral diene ligands enabled the asymmetric induction making chiral cyclobutylamine with excellent enantioselectivity. With the feasibility of catalytic alkenyl addition to the C=N bond, the scope of the C=N bond was expanded by using sulfonylhydrazones instead of imines (Chapter 5). Under mild and operationally simple reaction conditions, traceless endocyclic alkene synthesis could be achieved based on the merger of rhodium-catalysis and pericyclic rearrangement. Mechanistically, alkynylhydrazones gave cyclic hydrazide intermediate by the rhodium-catalysis with organoboronic acids, and it was decomposed to the product via allylic diazene with the extrusion of dinitrogen gas. Furthermore, chiral diene ligands could induce enantioselective addition of the alkenyl rhodium intermediate to the C=N bond, affording an enantioenriched C‒N stereocenter whose chirality is transferred to an allylic position via stereospecific rearrangement.Chapter 1. Transition Metal Vinylidene Mediated Catalytic Carbocyclization of Alkynes
1.1 Introduction 19
1.2 Carbocyclization by nucleophilic addition
1.2.1 Enol and enamine nucleophiles 19
1.2.2 Alkene and alkyne nucleophiles 21
1.2.3 Carbocyclization initiated by oxygen nucleophiles 25
1.3 Carbocyclization by pericyclic reaction
1.3.1 Electrocyclization 29
1.3.2 Cycloaddition 31
1.3.3 Sigmatropic rearrangement 34
1.4 Carbocyclization with disubstituted metal vinylidenes 36
1.5 Conclusion 45
1.6 Reference 47
Chapter 2. Rhodium-Catalyzed Carbocyclization of Alkynylenamines
2.1 Introduction 50
2.2 Results and discussion
2.2.1 Carbocyclization of N-benzyl alkynylenamine 55
2.2.2 Substrate scope 58
2.2.3 Asymmetric carbocyclization of alkynylenamines 60
2.2.4 Proposed mechanism and mechanistic studies 63
2.2.5 Dual catalysis: Merging rhodium-catalysis with organocatalysis 70
2.3 Conclusion and future studies 80
2.4 Reference 83
2.5 Experimental section
2.5.1 General remarks 85
2.5.2 Synthesis and characterization for compounds
2.5.2.1 General procedure for alkylation of β-ketoesters 85
2.5.2.2 General procedure for the alkynylenamines 88
2.5.2.3 General procedure for the rhodium-catalyzed carbocyclization of alkynylenamines 93
2.5.3 Determination of the enantiomeric excess 96
Chapter 3. Rhodium-Catalyzed Tandem Addition– Cyclization Reactions of Alkynes with Organoborons
3.1 Introduction 99
3.2 Tandem addition‒cyclization with unsaturated carbon‒heteroatom bonds 100
3.3 Tandem addition‒cyclization with unsaturated carbon‒carbon bonds 105
3.4 Conclusion 113
3.5 Reference 114
Chapter 4. Rhodium-Catalyzed Tandem Addition– Cyclization of Alkynylimines
4.1 Introduction 116
4.2 Results and discussion
4.2.1 Substrate scope 120
4.2.2 Asymmetric carbocyclization of alkynylimine 123
4.3 Conclusion 126
4.4 Reference 127
4.5 Experimental section
4.5.1 General remarks 128
4.5.2 Synthesis and characterization for substrates 128
4.5.3 General procedure for the rhodium-catalyzed tandem cyclization 131
4.5.4 Characterization for products 132
4.5.5 Procedure for enantioselective rhodium-catalyzed tandem cyclization 138
4.5.6 Preparation of the rhodium-diene complex 4.25 138
Chapter 5. Rhodium-Catalyzed Tandem Addition– Cyclization–Rearrangement of Alkynylhydrazones
5.1 Introduction 139
5.2 Results and discussion
5.2.1 Preliminary results 146
5.2.2 Optimization of reaction conditions 150
5.2.3 Substrate scope of organoboronic acids 153
5.2.4 Substrate scope of alkynylhydrazones 157
5.2.5 Arylative ring contraction of cyclohexenones 170
5.2.6 Competition experiments with alkynylaldehyde 173
5.2.7 Asymmetric carbocyclization of alkynylhydrazones 175
5.2.8 Mechanistic studies 182
5.3 Conclusion 186
5.4 Reference 187
5.5 Experimental section
5.5.1 General remarks 190
5.5.2 Synthesis and characterization for substrates 191
5.5.3 General procedure for the rhodium-catalyzed tandem reaction 215
5.5.4 Characterization for products 216
5.5.5 Competition experiments with alkynylaldehyde 246
5.5.6 Determination of the absolute stereochemistry of 5.35 247
5.5.7 Mechanistic studies 249Docto
