Development of Novel Synthetic Methods of Organic Compounds Using Ketene as a Building Block.

使用乙烯酮作为结构单元开发有机化合物的新合成方法。

• 批准号: 08651018
• 负责人: HASHIMOTO Yukihiko
• 金额: $ 1.41万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08651018/
• 关键词: Ketenes; Asymmetric Synthesis; the Staudinger Reaction; beta-Lactams; 1-Phenylethylamine; 2-Chloropyridinium; [2+2]Cycloaddition; フェニルエチルアミン

Ketenes are generally unstable and reactive species, and only a few stable monomeric ketenes are available. Ketenes are known as useful reagents since they have unique reactivity due to their characterisric sutucture. However, because of their lack of stability, application over a wide area in organic synthesis has not been achieved so far. This research project is concerned with the development of novel stereoselective reactions, novel type of reactions using a ketene as a key intermediate.It is well known that beta-lactams can be synthesized by the reaction between a ketene and an imine. Since beta-lactams structure is a fundamental skeleton found in an important class of antibiotics, we first examined the development of new asymmetric methodology by using a chiral imine. As a result, it was found that a chiral imine derived from 1-(2,6-dichlorophenyl) ethylamine gave the corresponding beta-lactams in good to excellent yields with high stereoselectivity. Next, we designed a ketene having a chiral oxazolidinone auxiliary derived from erythro-2-amino-1,2-diphenylethanol. The ketene was easily prepared from the corresponding carboxylic acid via dehydration reaction with a 2-chloropyridinium salt. The reaction of the ketene with inines proceeded smoothly to give the desired beta-lactams with almost comlete stereoselectivity. Ketenes are also known to react with alkenes as well as imines to afford cyclobutanones. So, next we investigated intramolecular [2+2] cycloaddition reaction of chiral ketenes having a double bond. As a result, we found that the reaction proceeded smoothly to give the corresponding cyclobutanone derivatives with high stereoselectivity.

酮类化合物通常是不稳定的活性物质，只有少数稳定的单体酮类化合物可用。烯酮由于其独特的结构而具有独特的反应活性，因此被称为有用的试剂。然而，由于它们缺乏稳定性，迄今尚未在有机合成中得到广泛的应用。本研究项目是关于新型立体选择反应的发展，新型的反应使用烯酮作为关键中间体。众所周知，烯酮和亚胺之间的反应可以合成-内酰胺。由于β -内酰胺结构是一类重要抗生素的基本骨架，我们首先通过使用手性亚胺来研究新的不对称方法的发展。结果发现，由1-（2,6-二氯苯基）乙胺衍生的手性亚胺具有较高的立体选择性，产率很高。接下来，我们设计了一种由红-2-氨基-1,2-二苯乙醇衍生的具有手性恶唑烷酮辅助物的烯酮。由相应的羧酸与2-氯吡啶盐脱水反应制备了烯酮。烯酮与茚酮的反应进行得很顺利，得到了几乎完全立体选择性的β -内酰胺。烯酮也可以与烯烃和亚胺反应生成环丁酮。因此，我们下一步研究具有双键的手性烯酮分子内[2+2]环加成反应。结果，我们发现反应进行顺利，得到相应的具有高立体选择性的环丁酮衍生物。

项目成果

S.Matsui, Y.Hashimoto, and K.Saigo: ""Application of erythro-2-Amino-1,2-diphenylethanol as a Highly Efficient Chiral Auxiliary. Highly Stereoselective Staukinger-Type beta-Lactam Synthesis Using2-Chloro-1-methylpyridinium Salt as a Dehydrating Agent"" Sy

S.Matsui、Y.Hashimoto 和 K.Saigo：“赤-2-氨基-1,2-二苯基乙醇作为高效手性助剂的应用。”

S.Matsui: "Application of erythro-2-Amino-1,2-diphenyleihanol as a Highly Efficient Chiral Auxiliary Highly Stereoselective Staudinger-Type β-Lactam Synthesis Using 2-Chloro-1-methylpyridinium Salt as a Dehydrating A gent" Synthesis. (印刷中). (1998)

S.Matsui：“赤-2-氨基-1,2-二苯基乙醇作为高效手性辅助高立体选择性施陶丁格型β-内酰胺合成的应用，使用2-氯-1-甲基吡啶鎓盐作为脱水剂”合成。 （出版中）。

S.Matsui: "Appljeation of erythro-2-Amino-1,2-diphenylethauol as a Highly Efficient Chiral Auxiliary Highly Stereos elective Staudiuger-Type P-Lactam Synthesis Using 2-Chloro-1-methyl-pyridiuium Salt as a Pehydrating Agent." Synthesis. (印刷中). (1998)

S.Matsui：“使用 2-氯-1-甲基-吡啶鎓盐作为脱水剂，将赤-2-氨基-1,2-二苯基乙醇作为高效手性辅助高立体选择性 Staudiuger 型 P-内酰胺合成的应用。 “综合。（印刷中）。（1998）