1.雙功能金雞納鹼催化 3-高醯基香豆素與亞甲基吲哚酮進行不對稱 (3+2) 環加成反應建構全碳掌性中心之螺環吲哚酮 2.經由兩性離子中間體進行化學選擇之威悌反應合成茚並- [1,2-b]吡咯
No Thumbnail Available
Date
2020
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
1.實驗使用起始物3-高醯基香豆素 (3-homoacyl coumarin) 與亞烷基吲哚酮(alkylidene oxindoles) ，藉由雙功能金雞納鹼催化劑催化逐步的(stepwise) (3+2) 環加成反應去建立具有對掌體選擇性 (enantioselective) 之螺環吲哚酮其架構中含有全碳的五環結構並且有連續五個立體中心，可以得到良好的產率以及立體選擇性，此外我們也更換亞烷基吲哚酮上的取代，包含兩種具有羰基取代的酯基 (ester group)、苯甲醯基 (benzyl group) 以及去除羰基之苯基 (phenyl group) 去比較羰基在氫鍵催化下的影響。放大反應證實此反應即使在克級條件下進行仍然能夠維持良好的產率以及立體選擇性。
關鍵字 : 香豆素、選擇性、螺環吲哚酮
2.第二部分的研究利用本實驗室過去在2012年所發表之磷兩性離子 (phosphorus zwitterion) 之合成策略，利用三組分反應(three-component reaction)建構新型磷兩性離子中間體，並在醯氯 (acyl chloride) 以及鹼的作用下，進行威悌反應建構茚並- [1,2-b]吡咯，出乎意料的是使用不同膦試劑能得到螺環噁二唑(spirooxadiazole)衍生物，經由探討發現利用不同親和性的膦試劑能夠影響其脫去與否，進而使得反應導向不同的結果。相比於過去合成茚並- [1,2-b]吡咯的策略，本篇提供一個全新的合成策略，不但能有良好的產率其產物的取代基也相當廣泛。
關鍵字 : 威悌反應、化學選擇性、茚並- [1,2-b]吡咯
1.The spirooxindole scaffolds are privileged heterocyclic motifs that are widely found in pharmacologically interesting compounds. Here, we describe a novel organocatalytic asymmetric stepwise (3+2) cascade reaction of 3-homoacylcoumarins and oxindole alkylidenes affording cyclopentane-fused spirooxindoles with five contiguous stereocenters including one quaternary carbon. Furthermore, the employment of the quinine-based squaramide bifunctional catalyst provided moderate to excellent yields (45-99%) and stereocontrol (2:1 to >20:1 dr, 61 to 99% ee) of the desired products. The expanded substrate scopes from esteryl and ketyl to aryl alkylidene oxindoles gave excellent results as well. A series of controlled experiments with these substrates, as mentioned above, revealed the mechanism of (3+2) cycloaddition is stepwise. Keywords : coumarin, stepwise (3+2) cycloaddition, stereocontrol 2.The pyrrole-containing substrates, indeno[1,2-b]pyrroles, have demonstrated remarkable biological activities in the earlier reports, such as antitumor activities. However, only few reports provided synthetic methods for this valuable indeno[1,2- b]pyrrole derivatives. Owing to their immense pharmaceutical importance, the development of new methodologies for the synthesis of indeno[1,2-b]pyrrole derivatives is highly desirable. Herein, we reported a facile synthesis of indeno[1,2-b]pyrrole derivatives via an indandione-oxime phosphorus zwitterion formation and chemoselective Wittig reaction process with indandione-oxime alkylidenes under mild conditions. Noteworthy, the present work has shown contradictory results from our reported betaacylation chemistry, which using similar substrate indandione alkylidenes. Furthermore, synthesis of spiro[indene-1,2'-[1,3,4]oxadiazol]-3(2H)-ones was realized with MePPh2. Keywords : indeno[1,2-b]pyrrole, chemoselectivity, wittig reaction
1.The spirooxindole scaffolds are privileged heterocyclic motifs that are widely found in pharmacologically interesting compounds. Here, we describe a novel organocatalytic asymmetric stepwise (3+2) cascade reaction of 3-homoacylcoumarins and oxindole alkylidenes affording cyclopentane-fused spirooxindoles with five contiguous stereocenters including one quaternary carbon. Furthermore, the employment of the quinine-based squaramide bifunctional catalyst provided moderate to excellent yields (45-99%) and stereocontrol (2:1 to >20:1 dr, 61 to 99% ee) of the desired products. The expanded substrate scopes from esteryl and ketyl to aryl alkylidene oxindoles gave excellent results as well. A series of controlled experiments with these substrates, as mentioned above, revealed the mechanism of (3+2) cycloaddition is stepwise. Keywords : coumarin, stepwise (3+2) cycloaddition, stereocontrol 2.The pyrrole-containing substrates, indeno[1,2-b]pyrroles, have demonstrated remarkable biological activities in the earlier reports, such as antitumor activities. However, only few reports provided synthetic methods for this valuable indeno[1,2- b]pyrrole derivatives. Owing to their immense pharmaceutical importance, the development of new methodologies for the synthesis of indeno[1,2-b]pyrrole derivatives is highly desirable. Herein, we reported a facile synthesis of indeno[1,2-b]pyrrole derivatives via an indandione-oxime phosphorus zwitterion formation and chemoselective Wittig reaction process with indandione-oxime alkylidenes under mild conditions. Noteworthy, the present work has shown contradictory results from our reported betaacylation chemistry, which using similar substrate indandione alkylidenes. Furthermore, synthesis of spiro[indene-1,2'-[1,3,4]oxadiazol]-3(2H)-ones was realized with MePPh2. Keywords : indeno[1,2-b]pyrrole, chemoselectivity, wittig reaction
Description
Keywords
香豆素, 螺環吲哚酮, 選擇性, 威悌反應, 化學選擇性, 茚並- [1,2-b]吡咯, coumarin, stepwise (3+2) cycloaddition, stereocontrol, chemoselectivity, wittig reaction, indeno[1,2-b]pyrrole