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Development of Asymmetric Acylation Reaction by Using Chiral Leaving Group and Its Application to the Synthesis of Useful Materials

手性离去基团不对称酰化反应的进展及其在有用材料合成中的应用

基本信息

批准号：
05680508
负责人：
KATSUKI Tsutomu
金额：
$ 1.28万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

This research was commenced with the study on asymmetirc reaction by employing chiral leaving group. First, optically active benzimidazole derivative prepared from (R)-mandelic acid was found to serve as an effective chiral leaving group in the asymmetric acylation of achiral amide enolate affording optically active alpha-alkyl-beta-oxoamide in up to 65% ee. This reaction was attempted to apply to the synthesis of a key synthetic intermediate of beta-lactam antibiotics. Although no optical yield was observed in the acylation of beta-lactam enolate, it became obvious that the acylated product, 3-acyl-beta-lactam, racemized easily different from the previous case. This result seemed to suggest the possibility of asymmetric reduction of racemic 3-acyl-beta-lactam by using chiral binap-Ru complex. Asymmetric acylation of allylmetal was found to be difficult though allylcopper was found to be a good reagent for allylation of acid chloride.On the other hands, new synthetic method of chiral imidazole derivatives was developed by using alkylation of carbonyl compounds with the lithiated imidazole bearing chiral tetrahydropyranyl group on nitrogen. The newly prepared imidazole derivatives were examined as chiral ligand in asymmetric reactions. Preliminary study on the mechanism of asymmetric reduction using oxazaborolidine which was developed by Istuno and Corey, suggested another possibility of mechanism for asymmetric induction. In the asymmetric alkylation of benzaldehyde with diethylzinc and chiral ligand of imidazole derivatives, up to 73%ee was achieved by introducing anthracene framework on imidazole derivative.Thus we succeeded in the development of asymmetric acylation of amide enolate by using chiral leaving group along with various new findings concerned with asymmetric reaction. Further studies are in progress.

本研究是从手性离去基团对不对称反应的研究开始的。首先，以（R）-扁桃酸为原料合成了光学活性苯并咪唑衍生物，发现其在非手性酰胺烯醇化物的不对称酰化反应中可作为有效的手性离去基团，得到光学活性α-烷基-β-氧代酰胺，其ee值高达65%，并尝试将该反应应用于β-内酰胺类抗生素的关键合成中间体的合成。虽然在β-内酰胺烯醇化物的酰化中没有观察到光学产率，但很明显，酰化产物3-酰基-β-内酰胺容易外消旋化，与以前的情况不同。这一结果表明手性联萘钌配合物可用于外消旋3-酰基-β-内酰胺的不对称还原。烯丙基铜是酰氯烯丙基化反应的良好试剂，但烯丙基金属的不对称酰化反应比较困难，另一方面，利用含手性四氢吡喃基的锂化咪唑与羰基化合物的烷基化反应，发展了手性咪唑衍生物的合成新方法。研究了新合成的咪唑衍生物作为手性配体在不对称反应中的应用。对Istuno和Corey提出的恶唑硼烷不对称还原反应机理进行了初步研究，提出了不对称诱导反应的另一种可能机理。在咪唑衍生物的手性配体和二乙基锌与苯甲醛的不对称烷基化反应中，通过在咪唑衍生物上引入蒽骨架，获得了高达73%ee的不对称烷基化反应，从而成功地发展了利用手性离去基团沿着的酰胺烯醇化物的不对称酰化反应。进一步的研究正在进行中。