以過渡金屬催化合成具官能基碳環及異員環新途徑之發展

Development of New Synthetic Approaches to Access Functionalized Carbocycles and Heterocycles by Transition Metal Catalysis

沙米爾(Samir Kundlik Pawar)

指導教授 ： 劉瑞雄

國立清華大學/理學院/化學系/博士(2015年)

摘要

Abstract (Chinese)

本文描述使用金與銀鹽類之有機合成轉換的新途徑之發展。藉由軟性親炔的金屬可使易取得的基質經由溫和、非對映選擇性、高效率地轉換成多種碳環、含氮或氧之雜環。為了更清楚地瞭解本文，本文分成四個章節。
第一章主要探討2-乙炔基芐醚與有機氧化物透過金催化環加成反應合成1,3-二氫異衍生物。這類以1,3-二氫異苯基呋喃為核心的化合物是自然界中最常見的結構之一，且十分廣泛的被應用在重要的結構以及生物學中。這種產物的核心結構是通過[4+ 1]環-α-羰卡賓和系留式醚類所構成。該催化劑的效用包括對苯基和不同醚類的各種取代。
第二章論述金以及銀催化炔醯胺、芳基氧雜環丁烷和芳基氮雜環丁烷進行一[4+2]環加成反應，形成六元雜環。氧雜環丁烷做為親核劑，而金--炔醯胺則為親電劑。在氮雜環丁烷的案例中，我們發現銀六氟銻比金催化劑更有效催化炔醯胺之[4+2]-環加成。此二環加成反應適用在合理的範圍內之炔醯胺、氧雜環丁烷以及氮雜環丁烷，進而表現其合成六元雜環之實用性，如6-氨基-3,4-二氫-2氫-吡喃和2-氨基-1,4,5,6-四氫吡啶。
第三章介紹炔醯胺分別與2H-氮環丙烯、疊氮烯烴透過金催化進行環加成，得到兩個不同類別的[3+2]或[4+3]環加成物。炔醯胺與2H-氮環丙烯類的環加成反應可得到吡咯類產物。而對於苯基取代富含電子的炔醯胺，與疊氮烯烴通過新穎的[4+ 3]環加成反應來形成-1H-苯基-[d]-氮雜產物。
第四章介紹透過共激活模式以1,6-二炔與-8-甲基喹啉N-氧化物合成出3-酮萘酚和3-酮基酚衍生物合成方法之發展。本反應的價值反應在其適用於廣泛的苯和非苯類衍生基質。

關鍵字

金催化 ； 和環 ； 炔醯胺 ； 氧化加成 ； 異員環

並列摘要

Abstract
This dissertation describes development of new synthetic organic transformations by using gold and silver salts. The use of these soft alkynophilic metals enables mild, diastereoselective and efficient transformations of a variety of readily available substrates to wide range of synthetically useful carbocyclic and nitrogen or oxygen containing heterocyclic products. For better understanding the thesis is divided into four chapters.
The first chapter deals with the Gold-catalyzed reactions of 2-ethynylbenzyl ethers with organic oxides for synthesis of 1,3-dihydroisobenzofuran derivatives through a formal cycloaddition reaction. Such 1,3-dihydroisobenzofuran core is one of the most commonly encountering skeletons in nature and the core scaffold has a wide spread application in structural and biological importance. The core structures of the resulting products are constructed through a formal [4+1] cycloaddition among α-carbonyl carbenoids and tethered ethers. The utility of this catalysis includes various substituents on phenyl groups and different ethers.

The second chapter deals with the Gold- and Silver-catalyzed [4+2] cycloaddition reactions of ynamides with aryl-oxetanes and aryl-azetidines to form six membered heterocycles. Oxetanes function as nucleophiles whereas gold--ynamides are present as electrophiles. In the case of azetidines, silver hexafluoroantimonate was found to be more active than gold catalyst in their [4+2]-cycloadditions with ynamides. The two cycloadditions are applicable to a reasonable range of ynamides, oxetanes and azetidines, thus manifesting their synthetic utility to access six-membered heterocycles such as 6-amino-3,4-dihydro-2H-pyrans and 2-amino-1,4,5,6-tetrahydropyridines.

The third chapter describes the Gold-catalyzed cycloadditions of ynamides with azidoalkenes or 2H-azirines to give [3+2] or [4+3] formal cycloadducts of two different classes. Cycloadditions of ynamides with 2H-azirine species afford pyrrole products. For ynamides substituted with an electron-rich phenyl group, their reactions with azidoalkenes proceed through novel [4+3] cycloadditions to deliver 1H-benzo[d]azepine products instead.

The fourth chapter presents development of a oxidative cyclizations of 1,6 diynes with 8-methylquinoline N-oxides through dual activation mode to achieve 3-keto naphthols and 3-keto phenol derivatives. The value of the reaction is reflected by their applicability to a broad range of benzene- and nonbenzene-derived substrates.

並列關鍵字

Gold-Catalyzed ； Formal cycloaddition ； Ynamides ； oxidative cyclizations ； Heterocycles

參考文獻

Chapter I

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