過渡金屬應用於雜環化合物合成之研究｜國立清華大學博碩士論文庫

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研究生：	庫馬 Manyam Praveen Kumar
論文名稱：	過渡金屬應用於雜環化合物合成之研究 Synthesis of Heterocyclic Compounds by Transition Metal Catalyzed Reaction: New Methodologies
指導教授：	劉瑞雄 Rai-Shung Liu
口試委員:
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：	2006
畢業學年度：	94
語文別：	英文
論文頁數：	349
中文關鍵詞：	雜環化合物合成、過渡金屬應用
外文關鍵詞：	Synthesis of Heterocyclic, Transition Metal Catalyzed Reaction
相關次數：	點閱：2 下載：0
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本論文內容討論一些過渡金屬催化反應及其在有機合成上的應用。為了方便和了解此內容，我們將其分成四個章節。第一、第三和第四章節討論釕金屬催化反應應用在有機合成上。可利用非環或環狀骨架經由有機金屬錯合物進行雜環環化或分子內環化
成功的合成雜環系統。
第一章節描述2-alkynyl-phenol-alkanol衍生物使用Tp[Ru]PF6經由6-endo-dig模式進行有效率選擇性的環化合成。此環化的實用性可明顯的利用在合成雜環系統，例如isochromene衍生物。這類的反應在有機合成上是很重要且具高度挑戰性的。
第二章節是利用[RhCl(CO2)]2催化環化環氧炔建立一個容易且有效率的合成途徑運用在合成2,5雙取代呋喃化合物。這有實用性的方法可被應用在合成複雜的天然物分子。而呋喃結構也經常出現在一些重要的天然物和藥物分子上。
第三章節描述使用Tp[Ru]PF6新的催化系統經由環氧酮有效率的重排反應可成功的合成1,2雙酮化合物。1,2雙酮化合物在天然物合成上都扮演著關鍵步驟。1,2雙酮化合物在有機物轉換上具有很大的變化性且在合成天然物或具生物活性結構分子是非常有潛力的前驅物。
　　第四章節描述使用Zn(OTf)2當催化劑的新合成方法可提供簡單有效率的步驟環化易取得的炔丙醇合成出吲哚、苯喃和噁唑。關於合成噁唑，我們使用Tp[Ru]PF6和Zn(OTf)2共同催化的方法。此合成的反應機構已被完整的說明。這重要的方法已經被用在雜環合成反應上。而吲哚、苯喃和噁唑在很多天然物中是很重要的骨架，因此持續發展新型合成方法是一個重要的目標。

The thesis discusses a few transition metal-catalyzed reactions and their application in organic systhesis. For convenience and better understanding, the thesis is divided into four chapters. The first and the last two chapters deals with ruthenium-catalyzed reactions and application in organic synthesis. The synthesis of heterocyclic systems from acyclic or cyclic building blocks is typically achieved through the use of the heteroannulation or intramolecular cyclization process from organometallic complexes.
The first chapter describes an efficient regioselective cyclization of 2-alkynyl-phenol-alkanol derivatives via 6-endo-dig mode catalyzed by Tp[Ru]PF6 catalyst. The synthetic utility of this cyclization is manifested in the synthesis of heterocylcles such as isochromene derivatives. These reactions are important and challenging topic in organic synthesis.
The second chapter establishes a facile, effective route for synthesizing 2,5-disubstituted furans via [RhCl(CO2)]2-catalyzed cyclization of epoxyalkanes. These useful method could be applied to the synthesis of complex natural products. Furan molecules are essential part of some important natural products and pharmaceuticals.
The third chapter describes the synthesis of 1,2-diketones via an efficient rearrangement of a,b-epoxyketones using a new catalytic system, Tp[Ru]PF6. These 1,2-diketone are key intermediates in the synthesis of a wide range of natural products. 1,2-Diketones and organic moieties could be subjected to a wide variety of further chemical transformations to give potential intermediates, as precursors for the synthesis of natural products as well biologically active compounds.

The last chapter describes a new methodology involving Zn(OTf)2 as catalyst providing an easy and effective approach for synthesizing indoles, benzofurans, and oxazoles through the cyclization of propargyl alcohols with commercially available starting materials. For the synthesis oxazoles, we have used co-catalyst Tp[Ru]PF6 along with Zn(OTf)2. The mechanism of this process was completely elucidated. These significant methods are applicable to the heterocylces synthesis. Indoles, benzofurans, and oxazoles moieties represents an important substructures in many natural products, and development of novel synthetic approaches to these skeletons continues to be an important goal.

ACKNOWLEDGEMENT                                            iii
ABSTRACT                                                       iv
LIST OF SCHEMES                                                vi
LIST OF TABLES                                                  xi
LIST OF FIGURES                                                 xii
LIST OF PUBLICATIONS                                           xiii
LIST OF ABBREATIONS                                            xiv
CHAPTER 1: An Efficient Regioselective Cyclization of 1-(2-alkynyl-Phenyl)-alkan-ol derivatives via 6-endo-dig mode Catalyzed by Ruthenium Complex.
Introduction                                               1
Results and Discussion                                      8
Conclusion                                               18
CHAPTER 2: A Highly Efficient Synthesis of Furan by Rhodium-Catalyzed
Cyclization of Internal Epoxyalkyne.
Introduction                                               30
Results and Discussion                                      42
Conclusion                                                51
CHAPTER 3: Highly Efficient Ruthenium Catalyzed Rearrangement of
α,β-Epoxyketones to 1,2-Diketones.
Introduction                                               68
Results and Discussion                                      80
Conclusion                                                91
CHAPTER 4: Zn(OTf)2-catalyzed cyclization of the Propargyl alcohols with
Anilines, Phenols and Amides for the Synthesis of Indoles, Benzofurans and
Oxazoles via different Regioselective Annulation.
Introduction                                              108
Results and Discussion                                     123
Conclusion                                               139
Experimental section                                       140
Crystal Structures                                         165
References                                               184
1H AND 13C NMR SPECTRA                                        188

                                

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4.3.0 Conclusion:
1. A new methodology with Zn(OTf)2 as a catalyst, we achieved a facile synthesis of indole, benzofuran and oxazole easily through the cyclization of propargyl alcohols with anilines, phenols and amides, with excellent yields and complete regioselectivies. The skeletal structures of indole products differ from those of benzofurans and oxazoles.
2. The mechanism of formation of indole and oxazole products, in which Zn(OTf)2 catalyzes the C(2)-addition of aniline and amide nucleophiles to propargyl alcohol moieties, was also elucidated. For indole formation, Zn(OTf)2 is active for not only the intramolecular cyclization of a-amino ketone intermediates but also for the isomerization of a-amino ketone intermediates through a 1,2-nitrogen shift.
3. Zn(OTf)2 shows similar reaction pathways for benzofuran and oxazole syntheses, except that in the resulting a-carbonyl intermediates do not undergo isomerization in the presence of Zn(OTf)2 catalyst.

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