Studies on New Methodologies via Heteroatom-Directed Conjugate Addition for Synthesis toward Solanoeclepin A

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研究生：	鄭佳怡 Cheng, Chia-Yi
論文名稱：	Studies on New Methodologies via Heteroatom-Directed Conjugate Addition for Synthesis toward Solanoeclepin A
指導教授：	磯部稔 Minoru Isobe
口試委員:	廖俊臣汪炳鈞林俊成陳清玉
學位類別：	博士 Doctor
系所名稱：	理學院 - 化學系 Department of Chemistry
論文出版年：	2012
畢業學年度：	101
語文別：	英文
論文頁數：	283
中文關鍵詞：	共軛加成反應、四員環、五員環、乙炔碸
外文關鍵詞：	heteroatom-directed conjugate addition, cyclbutane, Sulfonyl Acetylene
相關次數：	點閱：1 下載：0
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本論文之研究目的已開發新的合成方法，以建構五員環和四員環化合物，進而運用在天然物solanoeclepin A的合成上。其中我們先探討乙炔碸對於多種親核劑加成的反應性，依據親核劑的強度我們得到三種不同類型的產物 (i) 加成產物93, (ii) 加成(共軛加成)產物94與 (iii) 取代產物95。接著再利用分子內共軛加成環化反應可得到環戊酮化合物120。

另一方面，我們也利用具有光學活性(R)-香旱芹酮 87經由數部合成反應製備前驅物169。隨後利用heteroatom-directed conjugate addition方法誘導親核劑與環氧化合物169進行加成反應與陰離子環化反應，可合成得到環丁烷化合物170。

Contents
中文摘要    i
Abstract    ii
Acknowledgments    iii
Abbreviations    iv
Contents    vi
Figure Index    x
Table Index    xi

Chapter I. Introduction    1
I-1. Introduction of Heteroatom-Directed Conjugate Addition    1 
I-1-1 Heteroatom-Directed Conjugate Addition by - or-oxygen chelation    2
I-1-2 Heteroatom-Directed Conjugate Addition in the Synthesis of Natural Products    4
I-2. Introduction and Synthetic Strategy of Solanoeclepin A    6
I-2-1. Introduction and Synthetic Review of Solanoeclepin A    6
I-2-2. Cyclobutane Ring Formation through Heteroatom-Directed Conjugate Addition    10
I-3. Organometallic Reactions    13
I-3-1. 1,4-Addition by Utilizing Cuprate Reagents    13
I-3-2. Trialkylzincate Reagents    14
I-3-3. Applications of Trialkylzincate Reagent    15
I-4. Research Motif and Proposal    17
Chapter II. Results and Discussion    19
II-1. Addition of Nucleophiles to Sulfonyl Acetylene    19
II-1-1. Addition of Carbon Nucleophiles to Sulfonyl Acetylene    20
II-1-2. Addition of Heteroatom Nucleophiles to Sulfonyl Acetylene    29
II-1-3. Intramolecular nucleophile to form cyclopentanone through     conjugate addition    34
II-1-4. Introduction of the Angular Methyl Group at C3 Carbon    37
II-1-5. Synthesis of the Substitute of Acetyl Group at C2 Carbon    42
II-2. Cyclobutane Formation by Exploiting Heteroatom-Directed Conjugate Addition    44
II-2-1. Studies of the Synthesis of anti Epoxy Vinylsilane    44
II-2-2. Studies of the Synthesis of anti Epoxy Vinylsulfone    49
II-2-3. Studies of the Cyclobutane Ring Formation    52
II-3. Conclusion    58
Chapter III. Experimental and References    60
III-1. General    60
III-2. Experimental Procedure    62
III-2-1. Synthesis of compound 97b    62
III-2-2. Synthesis of compound 98b    62
III-2-3. Synthesis of compound 99b    63
III-2-4. Synthesis of compound 91b    63
III-2-5. Synthesis of compound 91a    64
III-2-6. Products by Carbon Nucleophiles to the Acetylenic Sulfones 91a and 91b.    65
III-2-7. Products by Heteroatom Nucleophiles to the Acetylenic Sulfones 91a /91b.    71
III-2-8. Synthesis of compound 117.    76
III-2-9. Synthesis of compound 123    77
III-2-10. Synthesis of compound 125    77
III-2-11. Synthesis of compound 126    78
III-2-12. Synthesis of compound 119    79
III-2-13. Synthesis of compound 120    80
III-2-14. Synthesis of compound 132    81
III-2-15. Synthesis of compound 135    82
III-2-16. Synthesis of compound 83b    83
III-2-17. Synthesis of compound 139    84
III-2-18. Synthesis of compound 142    85
III-2-19. Synthesis of compound 143.    86
III-2-20. Synthesis of compound 144    87
III-2-21. Synthesis of compound 145    88
III-2-22. Synthesis of compound 146    89
III-2-23. Synthesis of compound 147    90
III-2-24. Synthesis of compound 152    91
III-2-25. Synthesis of compound 153    92
III-2-26. Hydrosilylation of 153 under Various Conditions    93
III-2-27. Synthesis of compound 160    96
III-2-28. Synthesis of compound 161    97
III-2-29. Synthesis of compound 162    98
III-2-30. Synthesis of compound 163    99
III-2-31. Synthesis of compound 167    100
III-2-32. 1,2-Addition of a-Epoxy Ketone 167    101
III-2-33. Hydrosilylation of b-Acetylenyl Adducts 168    103
III-2-34. Lithium acetylide addition to 169 and Cyclobutane Ring Formation 170    105
III-2-28. Synthesis of bis-PNB ester cyclobutane 175    107
III-3 References    109
Appendix (I) X-ray data and NMR spectra of compounds    114
Appendix (II) Publishcation    267






















Figure Index
Figure 1. Syn-adduct by chelation with oxygen atom.    1
Figure 2. Diastereoselectivity by - or -chelating manner.    3
Figure 3. Solanoeclepin A    7
Figure 4. Ate complexes.    14
Figure 5. Comparison of a-adduct 102a between known compounds 111a and 111b…    23
Figure 6. HMBC experiment of anti-methyl adduct 102a.    24
Figure 7. NOESY experiment of anti-methyl adduct 102a.    24
Figure 8. Products of Vinylmagnesium bromide to 91a and 91b.    25
Figure 9. HMBC experiment of 106.    26
Figure 10. HMBC experiment of 107.    27
Figure 11. HMBC experiment of 108.    28
Figure 12. HMBC experiment of 109.    28
Figure 13. ORTEP of the crystal structure of 112b and 113b.    31
Figure 14. ORTEP of the crystal structure of 117.    33
Figure 15. 1H and 13C-NMR spectra of cyclopentanone 120.    37
Figure 16. 1H and 13C-NMR spectra of allene 139.    41
Figure 17. 1H and 13C-NMR spectra of allene 147 and 151.    46
Figure 18. ORTEP of the crystal structure of 152.    46
Figure 19. 1H-NMR spectra of 154, 155 and 156.    48
Figure 20. ORTEP of the crystal structure of 163.    50
Figure 21. ORTEP of the crystal structure of 169 and 173.    54
Figure 22. HMBC experiment of cyclobutene 170.    55
Figure 24. ORTEP of the crystal structure of 175    56
Table Index
Table 1. syn-Adduct was inducted by Methyllithium chelating with -oxygen atom...    2
Table 2. anti-Adduct was inducted by Nucleophile chelating with -hydroxyl group....    3
Table 3. Products by Carbon Nucleophiles to the Acetylenic Sulfones 91a and 91b.    22
Table 4. Chemical Shifts of Vinyl Proton    29
Table 5. Products by Heteroatom Nucleophiles to the Acetylenic Sulfones 91a /91b.    30
Table 6. Characteristic 1H-NMR spectra data of 147 and 151.    45
Table 7. Hydrosilylation of 153 was examined with various conditions.    47
Table 8. Characteristic 1H-NMR spectra data of 154, 155 and 156.    48
Table 9. Lithium acetylide addition to 169 and cyclobutane ring formation 170.    55


                                

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