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.

本研究从手性离去基团的不对称反应的研究开始。首先，发现由(R)-扁桃酸制备的光学活性苯并咪唑衍生物在非手性酰胺烯醇化物的不对称酰化中作为有效的手性离去基团，提供高达65% ee的光学活性α-烷基-β-草酰胺。该反应尝试应用于β-内酰胺抗生素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-内酰胺很容易外消旋，这与之前的情况不同。这一结果似乎表明使用手性 binap-Ru 络合物不对称还原外消旋 3-酰基-β-内酰胺的可能性。尽管烯丙基铜被发现是酰氯烯丙基化的良好试剂，但发现烯丙基金属的不对称酰化是困难的。另一方面，通过用带有手性的锂化咪唑对羰基化合物进行烷基化，开发了手性咪唑衍生物的新合成方法。氮上的四氢吡喃基。新制备的咪唑衍生物作为手性配体在不对称反应中进行了研究。 Istuno和Corey开发的oxazaborolidine对不对称还原机制的初步研究提出了不对称诱导机制的另一种可能性。在苯甲醛与二乙基锌和咪唑衍生物手性配体的不对称烷基化反应中，通过在咪唑衍生物上引入蒽骨架，实现了高达73%ee的反应。由此，我们成功地开发了利用手性离去基团和各种不同的手性配体对酰胺烯醇化物进行不对称酰化反应。有关不对称反应的新发现。进一步的研究正在进行中。