金和銀金屬催化炔轉化成高度官能化之有機分子骨架

Gold and Silver-Catalyzed Transformations of Alkynes into Highly Functionalized Organic Framework

洛虎(Kardile, Rahul Dadabhau)

指導教授 ： 劉瑞雄

國立清華大學/理學院/化學系所/博士(2021年)

摘要

Abstract (Chinese)

本篇論文描述利用金或銀催化劑開發新型有機合成轉化，利用這些金屬催化劑溫和、具選擇性及有效率和易取得的基質合成轉化成廣泛有用得複雜有機分子等特性，為了容易理解，將分成四個章節進行介紹。

第一章關於1,4-二炔-3-醇與異噁唑或苯並異噁唑的金催化[4+1]環化反應生成吡咯的衍生物。此反應之化學選擇性的控制是透過起初異噁唑攻擊較少立體阻礙的炔烴形成金碳烯，進一步誘導第二個炔基進行12-遷移反應。利用1,4-二炔-3-醇、異噁唑甚至苯並異噁唑基質合成高度應用於廣泛的範圍。

第二章α-重氮酯和亞胺之間的金屬催化反應生成獨特的氮丙啶衍生物已經廣為人知，而本篇文獻發表關於分別利用叔丁氧基羰基保護基衍生亞胺以及重氮酯在金和銀金屬催化下的兩種新型烯烴化反應。我們的反應機構研究顯示這些新型烯烴化反應涉及到起初重氮酯對金屬及亞胺複合體形成曼尼希加成中間體，隨後透過羅斯坎普反應形成α-芳基-β-氨基丙烯酸酯或者透過形成銀碳烯生成β-芳基-β-氨基丙烯酸酯。

第三章關於2-（1-炔基）-2-烯烴-1-酮與蒽合成的金催化[4+3]環化反應生成具有高度外立體選擇性(dr> 25:1)環氧苯二氮類產物。這種新型的金催化效用能應用於廣闊的基質，更重要的是這種[4+3]環化反應運用掌性金催化劑在溫和環境條件(DCM, 0 °C)下表現鏡像選擇性形式已經發展良好的結果，其鏡像異構物過剩率(ee%)範圍在88.0-99.9%之間。根據密度泛函理論計算結果，我們逐步推測出反應進行路徑以合理化優異的外立體選擇性。
第四章描述利用2-（1-炔基）-2-烯烴-1-酮和乙烯基重氮酮在金催化反應下生成非對稱芳香雜環取代三芳基甲烷。在催化反應過程中，乙烯基重氮酮攻擊含金呋喃基芐基陽離子形成觀察到的C(1)-加成產物，我們也注意到乙烯基重氮酮可以環化生成吡唑衍生物並可與呋喃基芐基陽離子反應生成含吡唑三芳基甲烷為N(5)-加成路徑。

關鍵字

催化 ； 金 ； 銀

並列摘要

Abstract
This dissertation describes the development of new synthetic organic transformations by using gold or silver catalysts. The use of these metals enables mild, selective, and efficient transformations of readily available substrates into wide range of synthetically useful complex organic molecules. For ease of understanding, this dissertation is divided into four chapters.
Chapter one is comprised of novel gold-catalyzed [4+1]-annulation reactions between 1,4-diyn-3-ols and isoxazoles or benzisoxazoles to yield pyrrole derivatives. The reaction chemoselectivity is controlled by an initial attack of an isoxazole at a less hindered alkyne to form gold carbenes, further inducing a 1,2-migration of a second alkyne group. A broad substrate scope of 1,4-diyn-3-ols, isoxazoles, and even benzisoxazoles highlighted the reaction utility.

Chapter two is comprised of two new olefination reactions between N-Boc imines and diazo esters, to yield phenylaminoacrylates with one gold catalyst, and to yield phenylaminoacrylates with AgOTf catalyst. Our mechanistic study indicates that both reactions proceed via formation of diazo containing Mannnich-addition intermediates, which subsequently undergo a Roskamp reaction for gold complex and formation of silver carbenes via 1,2-hydrogen shift. We disclose new versions of such imines/diazo ester reactions intermediates, that will be inspiring to design novel catalytic reactions.

Chapter three is comprised of gold-catalyzed [4+3]-annulations of 2-(1-alkynyl)-2-alken-1-ones with anthranils to yield epoxybenzoazepine products with excellent exo-diastereoselectivity (dr>25:1). The utility of this new gold catalysis is manifested by applicable substrates over a broad scope. More importantly, the enantioselective versions of these [4+3]-cycloadditions have been developed satisfactorily with chiral gold catalysts under ambient conditions (DCM, 0 °C); the ee levels range from 88.0–99.9%. With DFT calculations, we postulate a stepwise pathway to rationalize the preferable exo-stereoselection.

Chapter four is comprised of gold-catalyzed synthesis of nonsymmetrical heteroaryl-substituted triarylmethanes using 2-(1-alkynyl)-2-alken-1-ones and vinyldiazo ketones is described. In this catalytic sequence, vinyldiazo ketones attack gold-containing 3-furylbenzyl cations to form the observed C(1)-addition products. We also note that vinyldiazo ketones can be thermally cyclized to yield pyrazole derivatives, which can react with 3-furylbenzyl cations to afford pyrazole-containing triarylmethanes, corresponding to a N(5)-addition path.

並列關鍵字

Catalysis ； Gold ； Silver

參考文獻

Chapter 1 References

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