Enantioenriched Cyclic Allene Platform for Accessing Beyond-Racemic Events
- 주제(키워드) Cyclic Allene
- 주제(DDC) 621.042
- 발행기관 아주대학교 일반대학원
- 지도교수 서성은
- 발행년도 2026
- 학위수여년월 2026. 8
- 학위명 석사
- 학과 및 전공 일반대학원 에너지시스템학과
- 실제URI http://www.dcollection.net/handler/ajou/000000036590
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Cyclic allenes are highly strained, axially chiral intermediates that offer a unique platform for axial-to-point chirality transfer, enabling the rapid construction of multiple stereogenic centers in a single step. Despite their potential as versatile building blocks, the field has been hindered by a significant challenge: the lack of scalable and cost-effective access to enantioenriched precursors. Existing methods have largely relied on impractical asymmetric routes or expensive chiral resolutions, restricting previous investigations primarily to reactivity-focused studies using racemic forms. In this study, we report a preparatively scalable and economical asymmetric synthetic strategy for heteroatom-free cyclic allene precursors. The absolute configurations of these precursors were unambiguously determined through single- crystal X-ray crystallographic analysis of key late-stage intermediates. This synthetic breakthrough provided a robust platform for the first systematic and quantitative investigation of enantioretention across a broad range of cycloadditions, including （4+2）, （3+2）, and （2+2） manifolds. Our comprehensive dataset reveals unexpected deviations from conventional predictions based solely on cyclic allene racemization. These findings necessitate a revised mechanistic model involving a secondary racemizable intermediate, providing deeper insights into the stereochemical pathways of these transient species. Furthermore, we identify that azide partners exhibit uniquely excellent enantioretention in （3+2） cycloadditions—a phenomenon that is mechanistically rationalized herein. By overcoming long-standing synthetic barriers, this work not only advances the fundamental understanding of cyclic allene chemistry but also paves the way for their broader application in asymmetric synthesis. Keyword : Cyclic Allene
more목차
1. Introduction 1
2. Result and Discussion 7
2.1. Precursor Synthesis and Characterization 7
2.2. Cycloadditions 15
2.3. Mechanistic Study 21
2.4. Enantioselective Depletion 27
3. Conclusion 33
4. Experimental Section 34
4.1. General Information 34
4.1.1. Materials 34
4.1.2. Spectroscopic Methods 35
4.1.3. Procedure for Literature Survey 36
4.1.4. Previous Synthetic Strategies for Enantioenriched Kobayashi-Type Precursors 45
4.2. Preparation of Key Compounds 46
4.2.1. Preparation of Chiral Auxiliaries 46
4.2.2. Preparation of Alkylated Cyclohexenones 49
4.2.3. Preparation of Azomethine Imine 53
4.2.4. Preparation of Azidoarenes (Ar–N3) 54
4.3. Synthesis of Cyclic Allene Precursors 61
4.3.1. Our Synthetic Strategies for Enantioenriched Precursors 61
4.3.2. Synthesis of Enantioenriched Precursors 63
4.3.3. Synthesis of Racemic Precursors 95
4.3.4. Scale-Up Synthesis 102
4.3.5. Synthetic Preparation for Crystallography 110
4.3.6. Synthetic Preparation for Mechanistic Investigation 113
4.4. Cycloaddition Reactions 116
4.4.1. General Procedure 116
4.4.2. (4+2) Cycloaddition Reactions 117
4.4.3. (3+2) Cycloaddition Reactions with Nitrone 133
4.4.4. (2+2) Cycloaddition Reactions 155
4.4.5. Cycloaddition Reactions Using (R)-11 172
4.4.6. (3+2) Cycloaddition Reactions with Azomethine Imine 178
4.4.7. (3+2) Cycloaddition Reactions with Azidoarenes (Ar–N3) 183
4.5. Time-Course Experiments 206
4.5.1. General Procedure 206
4.5.2. Time-Course Experiments for (3+2) Cycloaddition Reactions with Azidobenzene 207
4.5.3. Time-Course Experiments for (4+2) Cycloaddition Reactions with Furan 211
4.5.4. Time-Course Experiments for (3+2) Cycloaddition Reactions with Nitrone 220
4.5.5. Time-Course Experiments for (2+2) Cycloaddition Reactions with MBL 229
4.6. Re-Exposure Experiments 238
4.6.1. General Procedure 238
4.6.2. Re-exposure Experiment with (R)-14 and (R)-3c 239
4.6.3. Re-exposure Experiment with (R)-14 and rac-3c 241
4.7. Crystallographic Data 243
4.7.1. Crystallization Methods 243
4.7.2. Experiment Details for Single-Crystal X-ray Diffraction 244
4.7.3. Procedures for Single-Crystal Structure Analysis 245
4.7.4. Summary 247
4.8. Theoretical Investigation 253
4.8.1. Computational Methods 253
4.8.2. Asymmetric α-Silylation 254
4.8.3. Comparison of Concerted, Stepwise, and Mixed Cycloaddition Pathways 256
4.8.4. Further Discussion on Pyramidal Inversion versus Elimination 282
4.8.5. Calculated Energies 284
4.8.6. Cartesian Coordinates of Calculated Structures 285
4.9. NMR Spectra of Characterized Compounds 315
5. Reference 486
