科研成果 科研团队 学者观点 学术论文 学生科研
 
首页-科学研究-网上学术厅-学术论文
Hydrogen-Bond-Directed Enantioselective Decarboxylative Mannich Reaction of b-Ketoacids with Ketimine
发布时间:2015-07-21        

The decarboxylative Mannich reaction (DMR) of b-ketoacidswith imines has emerged as a very important tool for thesynthesis of natural products and biologically active com-pounds. The elegant work of Robinson on the total synthesisof (?)-tropinone represents the first practical example ofutilizing the DMR as a key step in organic synthesis.[1]Herbert and co-workers[2]and Mangla and Bhakuni[3]thendeveloped a similar decarboxylative Mannich condensationsof b-ketoacids with D1-pyrroline and D1-piperideine for thesynthesis of biologically relevant alkaloids, such as septicine,phenanthroindolizidines, and cryptopleurine. Despite thesenotable achievements, little progress has been made in thedevelopment of an asymmetric version for this importantreaction. Recently, the group of Tian developed a chiral-auxiliary-based method in which b-ketoacids undergo highlydiastereoselective decarboxylative Mannich transformationwith optically active 2-(tert-butanesulfinyl-imino)glyoxyla-tes,[4a]and Lu and co-workers described a catalytic asymmet-ric DMR of b-ketoacids with aldimines to afford b-aminoketones with a maximum of ee value of 83%.[4b]However, allsuch studies have focused on the aldimine-based electro-philes. In contrast, the use of ketimines as the electrophilicacceptors for the decarboxylative Mannich reactions of b-ketoacids still remains a formidable challenge and there hasbeen no report in the literature, to date, of such a potentiallyuseful transformation.[5]The obvious benefits that hydrogen-bonding catalysis canoffer in asymmetric synthesis have been recognized in recentyears.[6]A unique characteristic of hydrogen-bonding catalysisis that the catalyst not only activates the reaction partnersthrough hydrogen-bond interactions, but also positions themin close proximity with the desired relative geometry, and assuch, the reaction is often facilitated in a synergistic manner,a manner similar to that of enzymatic catalysis. Herein, wereport the results of our efforts in developing a hydrogen-bond-directed enantioselective decarboxylative Mannichreaction of b-ketoacids by employing cyclic N-acyl ketiminesas the electrophilic acceptor (Figure 1). This new reaction wascooperatively promoted by saccharide-based bifunctionalorganocatalysts. The catalysts contain a tertiary amine andthiourea moieties which simultaneously activate the sub-strates and are responsible for excellent overall stereochem-ical control. The potential application of this catalyticasymmetric decarboxylative Mannich reaction was furtherexemplified in a highly enantioselective synthesis of the anti-HIV drug DPC 083

  1. 10.Hydrogen-Bond-Directed Enantioselective Decarboxylative Mannich Reaction of Beta-Ketoacids with Ketimines Application to the Synthesis of Anti-HIV Drug DPC?083.pdf
 
天大概况
校长致辞
现任领导
历届掌校人
大学章程
历史沿革
统计数据
机构设置
天大校区
天大新闻
天大要闻
教学科研
校友动态
学生活动
学院新闻
媒体声音
天大校报
视频新闻
科学研究
网上学术厅
科研机构
科研合作
科研服务
学术交流
学术期刊
人才培养
师资队伍
本科生教育
研究生教育
继续教育
高端培训
校园文化
天大故事
校园风光
校园生活
社会责任
文化研究
国际交流
海外访学
合作办学
国际认证
国际科研合作
留学生培养
孔子学院
地址:天津市南开区卫津路92号 | 邮编:300072
津ICP备05004358号 津教备0316号