One-pot Construction of Multi-stereocenters Utilizing Tandem Michael-aldol Reaction

利用串联迈克尔-羟醛反应一锅法构建多立体中心

• 批准号: 16390009
• 负责人: KATAOKA Tadashi
• 金额: $ 9.41万
• 依托单位: Gifu Pharmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390009/
• 关键词: tandem reaction; Michael reaction; aldol reaction; aldehyde; aldol; thione; Lewis acid; asymmetric synthesis; オキサゾリジンチオン; 連続反応; チオアミド; アセタール

1. Development of a new Michael-aldol reaction of thiolactams inducing malti-stereocenters : Reaction of N-cinnamoyl-oxazolidine-2-thione bearing a chiral center at the 4-or 5-position with an aldehyde was studied in the presence of a Lewis acid. A tricyclic compound with four new stereocenters was formed in a high chemical yield with a high diastereoselectivity.. Acetals diastereoselectively gave 2-(α-sulfanylbenzyl)-3-methoxypropionic acids in a high chemical yields. In the reactions the Lewis acid played both roles of an activator of enones and a generator of carbocations. The Lewis acid controlled the stereoselectivity of the Michael addition of the thione to an enone.2. Chemical transformation and utilization of the chiral Micheal-aldol products : The tricyclic compounds obtained from aldehydes were led to 1-phenyl-2-methylsulfanyl-1,3-propanediols possessing three consecutive chiral centers via acid hydrolysis, S-methylation and reduction. The Michael-aldol adducts derived from acetals were transformed into 2-(α-alkoxybenzyl)-3-sulfanylpropanols by the reductive removal of the chiral auxiliary. The chiral S-Acyl3-sulfanylpropanols acylated amines in high chemical yields, but the enantioselectivity of the reaction was very low.3. Intermolecular asymmetric Michael-aldol reactions using chiral cyclic thiocarbamates or thioureas : Several new cyclic thiocarbamates or thioureas were prepared and used for the asymmetric reactions of enones with aldehydes. The reactions proceeded more smoothly than the conventional ones but stereoselectivity of the reaction was low.We developed the asymmetric intramolecular Michael-aldol reactions of N-enoyl-oxazolidine・or thiazolidine-2-thiones with aldehydes or acetals in the presence of a Lewis acid and synthesized 1-phenyl-2-methylsulfanyl-1,3-propanediols or 2-(α-alkoxybenzyl)-3-sulfanylpropanols possessing three consecutive chiral centers.

1.硫内酰胺类化合物诱导多立体中心Michael-Aldol反应的研究：研究了在Lewis酸存在下，4-或5-位含手性中心的N-肉桂酰恶唑烷-2-硫酮与醛的反应。合成了一个具有四个新立体中心的三环化合物，具有高的化学产率和高的非对映选择性。缩醛非对映选择性地合成了2-(α-磺酰基)-3-甲氧基丙酸，化学产率较高。在反应中，路易斯酸既起到了烯酮激活剂的作用，又起到了碳正离子生成剂的作用。路易斯酸控制硫酮与烯的Michael加成反应的立体选择性。手性Michel-Aldol产物的化学转化及利用：以醛为原料合成的三环化合物经酸解、S甲基化和还原反应得到具有三个连续手性中心的1-苯基-2-甲硫基-1，3-丙二醇类化合物。由缩醛衍生的Michael-Aldol加合物通过手性助剂的还原脱除转化为2-(α-烷氧基苄基)-3-磺基丙醇。手性S-酰基-3-磺酰丙醇以较高的化学产率酰化了胺，但反应的对映选择性很低。使用手性环状硫代氨基甲酸酯或硫脲的分子间不对称Michael-Aldol反应：合成了几种新的环状硫代氨基甲酸酯或硫脲类化合物，用于烯酮与醛的不对称反应。在路易斯酸存在下，N-烯基-恶唑烷·或噻唑烷-2-硫酮与醛或缩醛的不对称分子内Michael-Aldol反应，合成了具有三个连续手性中心的1-苯基-2-甲硫基-1，3-丙醇或2-(α-烷氧基苄基)-3-磺基丙醇。

项目成果

Synthesis of 3-sulfanylpropanols containing three consecutive stereocenters via tandem Michael-aldol reaction of enoyl thioamides with acetals as key reaction

通过烯酰硫代酰胺与缩醛的串联迈克尔-羟醛反应合成含有三个连续立构中心的3-硫烷基丙醇

• 发表时间: 2005
• 期刊: Tetrahedron Letters 46,42
• 作者: 齊藤 亜紀夫;齊藤 亜紀夫;齊藤 亜紀夫;齊藤 亜紀夫;齊藤 亜紀夫;齊藤 亜紀夫;齊藤 亜紀夫;齊藤 亜紀夫;齊藤 亜紀夫;齊藤 亜紀夫;齊藤 亜紀夫;齊藤 亜紀夫;齊藤 亜紀夫;齊藤 亜紀夫;斎藤 亞紀夫;Shinichi Watanabe;Shinichi Watanabe;Shin-ichi Watanabe;Hironori Kinoshita
• 通讯作者: Hironori Kinoshita

One-pot Coupling of α,β-Unsaturated Carbonyl Compounds Bearing a Chalcogen Group and Electrophiles Using a Lewis Acid

使用路易斯酸对带有硫属基团的 α,β-不饱和羰基化合物和亲电子试剂进行一锅偶联

• 发表时间: 2006
• 期刊: Ann.Proc.Gifu Pharm.Univ. 55
• 作者: C.Mukai;M.Ohta;H.Yamashita;S.Kitagaki;Masahito Ochiai;Masahito Ochiai;Masahito Ochiai;kazunori Miyamoto;T.Kataoka
• 通讯作者: T.Kataoka