透過原子經濟性反應以金金屬催化炔類成官能基多樣化雜環

Gold-catalyzed Transformations of Alkynes into Highly Functionalized Heterocycles via Atom-economy Process

瑞吉(Sahani, Rajkumar Lalji)

指導教授 ： 劉瑞雄

國立清華大學/理學院/化學系所/博士(2017年)

摘要

本論文描述利用金和銀催化劑發展新的有機催化反應。利用這些金屬可以促使反應以易於取得的起始物經由溫和、具選擇性且有效率地進行轉換並獲得雜環產物。本論文共分為四章以利於理解。

第一章是利用炔酰胺與疊氮烯或2H-氮丙啶藉由金催化環加成能得到三類產物，分別為[3 + 2] - 或[4 + 3] - 環加成產物。當用具有酯基的烷基（或氫）取代Cβ-取代基-2H-氮丙啶時，炔酰胺與2H-氮丙啶物質的環加成反應能產生兩個區域選擇性的吡咯產物。 對於具豐電子的苯基取代基之炔酰胺，它們與疊氮烯能進行新穎的[4 + 3] - 環加成反應進行，並得到1H-苯並[d]-氮雜產物。

第二章是利用環氧化物或氧雜環丁烷能和丙炔酸叔丁酯衍生物順利進行金催化環化反應[4 + n]-（n = 3,4），並有效地產生七或八元環氧產物。 在[4 + 3]環化反應中，產物分析顯示環氧化物進行分子內SN2攻擊後依然能保留立體化學。我們還發現了一種由叔丁基丙酸酯與γ-內酯進行[4 + 5]環化反應，以表示此反應能用於中等大小的環類化合物。

於第三章我們開發了兩個新的藉由金催化對異噁唑與丙炔酸酯進行環化反應。大多數異噁唑會直接對炔進行間位攻擊而得到[4 + 1]-環化產品;該過程會導致丙炔酸酯容易進行炔裂解。無取代的異噁唑能進行具區域選擇性的氮原子攻擊得到[2 + 2 + 1] / [4 + 2]-環化產物。我們假設這兩個反應會先分別行成七元雜環中間體，在進行反應得到產物。

於第四章我們得到了一個新的藉由金催化對鄰氨基苯與丙酸鹽進行環化反應。大部分鄰氨基苯與丙酸鹽都會遵循氧原子攻擊路徑而得到[4 + 2] / [4 + 1]環化而得到環氧乙烯 [2,3-c]喹啉-2-羧酸酯產物，有些具有電子富集取代基的丙炔酸酯和鄰氨基苯甲酸能得到喹諾酮和喹啉-4（1H）-酮衍生物，是藉由它們相應的氧化烯[2,3-c]喹啉-2-羧酸酯進行重排而得。使用Au（I）和Zn（II）進行中繼催化，也可以將鄰氨基苯和丙炔酸酯進行一鍋反應合成高含氧四氫喹啉。

關鍵字

金金屬催化反應 ； 同相金金屬催化 ； 雜環合成 ； 和環反應 ； 還化反應 ； 有機轉換反應

並列摘要

This dissertation describes development of new synthetic organic transformation using gold and silver catalysts. The use of these metals enable mild, selective and efficient transformation to give a range of heterocyclic products from readily available substrates. This thesis is divided into four chapters for ease of understanding.

Chapter one is comprised of Gold-catalyzed cycloadditions of ynamides with azidoalkenes or 2H-azirines to give [3+2]- or [4+3]-cycloadducts in three classes. Cycloadditions of ynamides with 2H-azirine species afford pyrrole products in two regioselectivities, when the Cβ-substituent 2H-azirine is replaced from an alkyl (or hydrogen) with an ester group. 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.

Chapter two is comprised of Gold-catalyzed [4+n]-annulations (n = 3, 4) of tert-butyl propiolate derivatives with epoxides or oxetanes to yield seven- or eight-membered oxacyclic products efficiently. In the context of the [4+3]-annulations, product analysis reveals a retention of stereochemistry in an intramolecular SN2 attack of an epoxide. We also report a [4+5]-annulation between one tert-butyl propiolate and γ-lactol, to manifest the utility toward medium-sized rings.

Chapter three is comprised of development of two new gold-catalyzed annulations of isoxazoles with propiolates. Most isoxazoles follow an initial O-attack at alkynes to afford [4+1]-annulation products; this process results in a remarkable alkyne cleavage of initial propiolates. Unsubstituted isoxazoles proceed through a N-attack regioselectivity to yield formal [2+2+1]/[4+2]-annulation products. We postulate that these two annulation products arise initially from two seven-membered heterocyclic intermediates, further preceding to products.

Chapter four is comprised of a distinct gold-catalyzed annulation between anthranils and propiolates. Most of anthranils and propiolates follow a O-attack pathway to enable [4+2]-annulations, yielding oxireno[2,3-c]quinoline-2-carboxylates; Some propiolates and anthranils having electron rich substitutions resulted in quinolone and quinolin-4(1H)-one derivatives. One-pot synthesis of highly oxygenated tetrahydroquionolines from anthranils and propiolates is also achived through relay catalysis with Au(I) and Zn(II) catalysts.

並列關鍵字

Gold-catalyzed reaction ； Homogeneous gold-catalysis ； Heterocycle synthesis ； Annulation reaction ； Cyclization reaction ； Organic transformation

參考文獻

[1] Liming Zhang, Acc. Chem. Res., 2014, 47, 877-888.

[11] M. S. Novikov, A. F. Khlebnikov, Tetrahedron, 2013, 69, 3363-3401.

[12] K. Isomura, S. Kobayashi, H. Taniguchi, Tetrahedron Lett. 1968, 9, 3499-3502.

[13] H. Alper, J. E. Prickett, J. Chem. Soc., Chem. Commun. 1976, 483.

[14] D. F. Taber, W. Tian, J. Am. Chem. Soc. 2006, 128, 1058-1059.