Development of Novel Asymmetric Synthetic Reactions

新型不对称合成反应的发展

基本信息

批准号：
60870075
负责人：
KOGA Kenji
金额：
$ 6.08万
依托单位：
University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research
财政年份：
1985
资助国家：
日本
起止时间：
1985 至 1986
项目状态：
已结题

项目摘要

1. Asymmetric Alkylation Reactions via Chiral Chelated IntermediatesExaminations were made on the asymmetric alkylation reactions based on the concept of fixing the reactive conformation by chelation. It is shown that this concept is applicable successfully to the asymmetric Michael reaction. Thus, chiral chelated lithioenamines were prepared by condensation of L-valine ester and <beta> -keto esters followed by metalation. The reaction of these lithioenamines with di-tert-butyl methylenemalonate afforded, after hydrolysis, both enantiomers of the corresponding Michael adducts, depending on the combination of solvents and additives used. This strategy was found to be applicable also to the enantioselective asymmetric Michael reaction.2. Asymmetric Alkylation Reaction using Optically Active Butyrolactone and ButyrolactamBoth enantiomers of <gamma> -hydroxymethyl- <gamma> -butyrolactone were found to be prepared easily and in quantity from inexpensive L-glutamic acid, and were found to be … More useful chiral synthons for the asymmetric synthesis of antileukemic natural products, such as megaphone and spatol. In the course of the above synthetic efforts, it has become clear that the corresponding <gamma> -hydroxymethyl- <gamma> -butyrolactam, also prepared in optically pure form from L-glutamic acid, is a highly useful chiral reagent in asymmetric synthesis due to its unusual conformation. Novel method for the diastereoselective asymmetric synthesis of <beta> -substituted carboxylic acids using this lactam was developed.3. Enantioselective Asymmetric Synthesis using Chiral Lewis Acids and Chiral BasesEnantioselective Diels-Alder reaction catalyzed by optically active alkoxyaluminum dichlorides as chiral Lewis acids was further developed. Enantioselective deprotonation reaction of prochiral cyclic carbonyl compounds having <sigma> -plane in their molecules was realized by using chiral lithium amide bases. The products were isolated as trimethylsilyl enol ethers, which are chemically equicalent to enolate anions. This method should be applicable widely for the synthesis of various chiral synthons. Some mechanistic explanations of this reaction were proposed. Less

1。基于螯合通过固定反应性概念的概念，通过手性螯合中间二硫代反应进行了非对称烷基化反应。结果表明，该概念成功地适用于非对称的迈克尔反应。这是通过L-羟酯和<beta> -Keto酯的缩合制备手性螯合的锂苯胺，然后进行金属化。这些岩氧甲胺与二丁基甲基苯甲酸酯的反应得到了水解后，相应迈克尔的两个对映异构体，取决于使用的溶液和添加剂的组合。发现该策略也适用于对映选择性不对称的迈克尔反应2。 Asymmetric Alkylation Reaction using Optically Active Butyrolactone and Butyrolactone Both enantiomers of <gamma> -hydroxymethyl- <gamma> -butyrolactone were found to be prepared easily and in quantity from inexpensive L-glutamic acid, and were found to be … More useful chiral synthons for the asymmetric synthesis of antileukemia natural products, such as megaphone and spatol。在上述合成工作的过程中，很明显，相应的<gamma> - 羟甲基 - <gamma> -butyrolactam，也从L-谷氨酸中以光学纯的形式制备，是一种非常有用的手吉剂试剂，这是由于其非对称的合成而由于其不良构象而导致的不对称合成。使用该乳胶的<beta>取代羧酸的非对映选择性不对称合成的新方法已开发。3。进一步开发了使用手性刘易斯酸和手性碱基选择性的DIELS-ALDER反应的对映射性不对称合成，这些反应被光学活跃的烷氧基二氯酸酯作为手性刘易斯酸催化。通过使用手性锂酰胺基碱，实现了其分子中具有<sigma>平面的对照式质子化反应。将产物分离为三甲基硅烷基烯醇醚，化学上等效于烯烃。该方法应广泛适用于各种手性合成子的合成。提出了对该反应的一些机械解释。较少的