Development of Novel Asymmetric Synthetic Reactions

1. 手性螯合中间体的不对称烷基化反应基于螯合固定反应构象的概念，对不对称烷基化反应进行了检验。结果表明，这一概念成功地适用于不对称迈克尔反应。因此，通过l -缬氨酸酯和< β > -酮酯缩合，然后金属化制备手性螯合锂胺。这些锂胺与二叔丁基甲基enemalonate发生反应，水解后，根据溶剂和添加剂的组合，产生相应的Michael加合物的两种对映体。该策略同样适用于对映选择性不对称Michael反应。< γ > -羟甲基- < γ > -丁内酯对映体均以廉价的l-谷氨酸为原料，可方便、大量地制备出< γ > -羟甲基- < γ > -丁内酯对映体，是抗白血病天然产物（如扩音剂和spatol）的不对称合成物。在上述合成过程中，我们已经清楚地看到，相应的< γ > -羟甲基- < γ > -丁内酰胺，也是由l-谷氨酸以光学纯形式制备的，由于其不同寻常的构象，在不对称合成中是一种非常有用的手性试剂。建立了以该内酰胺为原料非对映选择性不对称合成< β > -取代羧酸的新方法。手性路易斯酸和手性碱对映选择性不对称合成进一步发展了以旋氧二氯化铝为手性路易斯酸催化的对映选择性diols - alder反应。利用手性锂酰胺碱，实现了分子中<sigma> -平面的前手性环羰基化合物的对映选择性去质子化反应。产物分离为三甲基硅烯醇醚，其化学性质等同于烯酸阴离子。该方法可广泛应用于各种手性合成物的合成。对这一反应提出了一些机理解释。少

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