서성은 최명수 2024-02 33761 https://aurora.ajou.ac.kr/handle/2018.oak/39374 학위논문(석사)--에너지시스템학과,2024. 2 The cyclic allene, first identified by Wittig in 1966, is a highly reactive intermediate with significant strain energy, similar to aryne, yet it is distinctively advantageous for its inherent chirality, attributable to its asymmetric axis, making it an advantageous building block in the synthesis of complex compounds. Despite the seminal discovery of cyclic allene by Wittig, the compound has received comparatively less attention over an extended period, especially when contrasted with aryne. The chiral sp3 carbon ring, synthesized through organic reactions of cyclic allene, serves as a versatile backbone for various bioactive molecule derivatives, maintaining the unique chirality of cyclic allene. The potential utility of cyclic allene as a building block for constructing stereochemically complex and structurally diverse compounds, especially for substances with a three-dimensional structure, is explored. Previous studies relied on racemic mixture of cyclic allene precursors obtained through chiral Supercritical fluid chromatography (SFC) separation to isolate single enantiomer. However, this approach demands diverse conditions suitable for different forms of cyclic allene precursors, necessitating numerous chiral columns and incurring substantial efforts and costs to establish a chiral SFC system. Due to the inherent high strain energy in cyclic allene, it is commonly employed in precursor, functionalized a silyl and triflate group. The in situ generation of cyclic allene is facilitated using F– sources, actively participating in the reactions. In our study, we employed SAMP ((S)-2-(methoxymethyl)pyrrolidine-1-amine)), developed by Enders and Corey in 1966, as a chiral auxiliary to synthesize enantioenriched cyclic allene precursors. Starting from commercially affordable L- proline, the synthesis of SAMP ((S)-2-(methoxymethyl-l)pyrrolidine-1-amine) involves a six step process, with the only purification requirement occurring during the final step through distillation. We successfully formed a single diastereomer through condensation and silylation reactions between SAMP and cyclohexanone, synthesizing a cyclic allene precursor with 99% enantiomeric excess (ee) optical purity. In 2018, Garg group's research highlights the key role of α-substituents in controlling racemization energy and driving stereoretentive reactions in cyclic allene. Therefore, we functionalize the α-position of cyclohexanone derivatives with various substituents to synthesize cyclic allene precursors with high optical purity. 1. Introduction 1_x000D_ 2. Result and Discussion 9_x000D_ 2.1. Synthesis of SAMP ((S)-2-(methoxymethyl)pyrrolidine-1-amine)) 9_x000D_ 2.2. Synthesis of Enantioselective Cyclic Allene Precursors via Cyclohexanones 10_x000D_ 2.3. Synthesis of Enantioselective Cyclic Allene Precursors via α-Functionalized Cyclohexanones 11_x000D_ 2.4. Detour of Approach 1 for Synthesis of Enantioenriched Cyclic Allene Precursor: 2-Methylcyclohexanone as Starting Material 15_x000D_ 2.4.1. Optimization of The Condensation Reaction (Challenge 2) 16_x000D_ 2.4.2. Optimization of The Silylation Reaction (Challenge 3) 19_x000D_ 2.4.3. Optimization for Ozonolysis Step (Challenge 4) 21_x000D_ 2.5. Synthesis of Enantioselective Cyclic Allene Precursors via γ-Functionalized Cyclohexanones 23_x000D_ 3. Conclusion 25_x000D_ 4. Experiment Section 27_x000D_ 4.1. General Information 27_x000D_ 4.2. General procedure for synthesis of SAMP 28_x000D_ 4.3. Procedure for synthesis of cyclic allene precursor 31_x000D_ 4.4. Procedure for recycling of SAMP 33_x000D_ 4.5. Procedure for synthesis of methyl-substituted cyclic allene precursor 33_x000D_ 4.6. General Procedure for Synthesis of Enantioselective Cyclic Allene Precursors via γ-Functionalized Cyclohexanones 36_x000D_ 4.7. Analytical HPLC data of cyclic allene precursor 38_x000D_ 4.8. Analytical data of the products 42_x000D_ 4.9. NMR Spectra of the Products 52_x000D_ 5. Reference 66_x000D_ eng The Graduate School, Ajou University 아주대학교 논문은 저작권에 의해 보호받습니다. Development of Enantioenriched Cyclic Allene Precursor via Stereoselective Derivatization of α-Silylcyclohexenones Thesis 아주대학교 대학원 Choi Myungsoo 일반대학원 에너지시스템학과 2024-02 Master https://dcoll.ajou.ac.kr/dcollection/common/orgView/000000033761 Cyclic allene Cyclic allene precursor Enantioselectivity