Asymmetric Protonation of Enolates with Optically Active Imides as Proton Sources

以光学活性酰亚胺作为质子源的烯醇化物的不对称质子化

• 批准号: 08455423
• 负责人: YANAGISAWA Akira
• 金额: $ 2.5万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 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-08455423/
• 关键词: Asymmetric Protonation; Optically Active Imide; Enantioselectivity; Enolates; Protonating Agent; Kemp's Tricarboxylic Acid; 2-Oxazoline; 2-Alkylcycloalkanone; kempのトリカルボン酸; 2-アルキルシクロアルカノン

Asymmetric protonation of prochiral metal enolates is an effective route to optically active carbonyl compounds. Although a number of groups have made important contributions to the continuing progress in this process, most of these are the reactions of enolates having polar groups including amino, hydroxyl, or phenyl groups, and there have been few satisfactory reports on the asymmetric induction of enolates of simple ketones such as 2-methylcyclohexanone. We have already reported that the new chiral proton source, (S,S) -or (R,R) -imide, which possesses an asymmetric 2-oxazoline ring, can be easily prepared from Kemp's tricarboxylic acid and (1R,2S) -or (1S,2R) -2-amino-1,2-diphenylethanol, and protonates various lithium enolates of alpha-monoalkylatedcycloalkanones with excellent to moderate enantioselectivity.In this research, we further examined the asymmetric protonation of simple prochiral metal enolates with the chiral imide and related imides. An increase in enantioselectivity … More was observed in the asymmetric protonation of prochiral lithium enolates with (S,S) -imide using lithium salt as an additive. For example, (R) -enriched 2-n-pentylcyclopentanone was obtained in a nearly quantitative yield with 90% ee when the corresponding lithium enolate was generated in the presence of 5 equiv of LiBr in Et_2O and was protonated with (S,S) -imide in THF.Higher enantioselectivity was observed for the reaction of lithium enolate of 2-methylcyclohexanone with optically active 1-cyclohexylethylamine derived (S) -or (R) -imide, which possesses a chiral amide group, than with (S,S) - or (R,R) -imide. Noteworthy was the fact that the enantioselectivity was highly dependent on the steric bulkiness of alkyl substituents of cyclohexane ring of the imide. These chiral imides were further successfully applied to a diastereoselective protonation of a chiral enolate. When the lithium enolate of (-) -menthone was protonated by (S,S) -imide or (R) -imide, cis-ketone was the major product formed. In contrast, a high trans-selectivity was obtained for the reaction with (R,R) -imide or (S) -imide. The catalytic process of this diastereoselective protonation has been realized using a catalytic amount of these chiral imides and stoichiometric amount of an achiral proton source. Less

前手性金属烯醇盐的不对称质子化反应是制备光学活性羰基化合物的有效途径。尽管许多研究小组对该方法的持续进展做出了重要贡献，但其中大多数是具有极性基团（包括氨基、羟基或苯基）的烯醇化物的反应，并且关于简单酮（如2-甲基环己酮）的烯醇化物的不对称诱导的令人满意的报道很少。我们已经报道了由肯普三羧酸和（1 R，2S）-或（1 S，2 R）-2-氨基-1，2-二苯基乙醇可以很容易地制备具有不对称2-恶唑啉环的新的手性质子源（S，S）-或（R，R）-酰亚胺，并以优异到中等的对映选择性质子化α-单烷基化环烷酮的各种烯醇化锂。我们进一步研究了简单的前手性金属烯醇化物与手性酰亚胺和相关酰亚胺的不对称质子化。增加对映体选择性 ...更多信息 在前手性烯醇锂与（S，S）-酰亚胺的不对称质子化反应中，以锂盐为添加剂，观察到了一个不对称质子化反应。例如，当在Et_2O中5当量LiBr的存在下生成相应的烯醇化锂并用（S，2-甲基环己酮的烯醇化锂与光学活性的（S）-或（R）-环己基乙胺的反应具有较高的对映选择性- 酰亚胺，其具有手性酰胺基团，而不是（S，S）-或（R，R）-酰亚胺。值得注意的是，对映选择性高度依赖于酰亚胺的环己烷环上的烷基取代基的空间体积。这些手性酰亚胺进一步成功地应用于手性烯醇化物的非对映选择性质子化。（-）-薄荷酮烯醇化锂与（S，S）-酰亚胺或（R）-酰亚胺质子化时，主要生成顺式酮。相反，对于与（R，R）-酰亚胺或（S）-酰亚胺的反应，获得了高的反式选择性。这种非对映选择性质子化的催化过程已经实现了使用催化量的这些手性酰亚胺和化学计量量的非手性质子源。少

项目成果

A.Yanagisawa: "Diastereoselective Protonation of Chiral Enolate with Chiral Iimides" Synlett. 956-958 (1997)

A.Yanagisawa：“手性烯醇化物与手性酰亚胺的非对映选择性质子化”Synlett。

A.Yanagisawa: "Diastereoselective Protonation of Chiral Enolate with Chiral Imides" Synlett. 956-958 (1997)

A.Yanagisawa：“手性烯醇化物与手性酰亚胺的非对映选择性质子化”Synlett。

A.Yanagisawa: "Enantioselective Protonation of Prochiral Enolates with Chiral Imides" Tetrahedron. (印刷中).

A.Yanagisawa：“前手性烯醇化物与手性酰亚胺的对映选择性质子化”四面体（正在出版）。

A.Yanagisawa: "Comprehensive Asymmetric Catalysis" Springer (印刷中),

A.Yanagisawa：“综合不对称催化”Springer（印刷中），

A.Yanagisawa et al: "Diastereoselective Protonation of Chiral Enolate with Chiral Imides" Synlett. 956-958 (1997)

A.Yanagisawa 等人：“手性烯醇化物与手性酰亚胺的非对映选择性质子化”Synlett。