Enantioselective Synthetic Reactions using Chiral Lithium Amide Bases

使用手性氨基锂碱的对映选择性合成反应

• 批准号: 03403023
• 负责人: KOGA Kenji
• 金额: $ 20.99万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (A)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03403023/
• 关键词: Asymmetric deprotonation; Asymmetricalkylation; Chiral lithium amide; Asymmetric protonation; Asymmetric catalytic reaction; Enantioselective reaction; Ligand exchange; Multinuclear NMR; キラル塩基; 不斉合成; 不斉アルドール反応; 不斉プロント化; メカニズム; リチウムアミド; X線結晶解

Studies using deuterated cyclohexanone derivatives determined the protons that are selectively deprotonated in the asymmetric deprotonation reactionsThe stereochemistry of the asymmetric alpha-alkylation of cyclic ketones was clarified on the basis of the reactions with 4-substituted cyclohexanonesAsymmetric protonation of achiral enolates was achieved, based on which the method to convert racemic ketones into optically active ones was established. Studiesusing deuterated compounds clarified that this protonation proceeded through protonation of chiral aminesThe solution structures of three chiral lithium amides were determined by ^6Li and ^<15>N-NMR spectroscopy, and their crystal structures were determined by X-ray analysis. The solution structure (agregation state) was able to be controlled by strong external ligands. The relationship between these results and the actual reactions was clarified.The asymmetric deprotonation reactions described above were extended to catalytic asymmetric reactions, the mechanism of which was proposedCatalytic asymmetric alkylation was successfully achieved with high efficiency. The mechanistic study is in progress.Asymmetric aldol and Darzens reactions using chiral bases were achieved

1.以氘代环己酮衍生物为研究对象，确定了在不对称去质子化反应中选择性去质子的质子。2.以4-取代环己酮为例，阐明了环酮不对称α-烷基化反应的立体化学。3.实现了非手性烯醇化物的不对称质子化，并在此基础上建立了外消旋酮转化为光学活性酮的方法。用~ 6Li和~ 1H-NMR确定了三种手性氨基锂的溶液结构<15>，用X射线衍射确定了它们的晶体结构。溶液结构（聚集态）能够通过强的外部配体控制。将上述不对称去质子化反应推广到催化不对称反应中，并提出了催化不对称反应的机理，成功地实现了催化不对称烷基化反应。反应机理研究正在进行中，实现了手性碱催化的不对称Aldol和Darfur反应

项目成果

Kazumasa Aoki: "Enantioselective Deprotonation of 4-Substituted Cyclohexanones by Chiral Lithium Amides Having a Fluorine-containing Group" Tetrahedron Letters. 34. 1505-1508 (1993)

Kazumasa Aoki：“具有含氟基团的手性氨基锂对 4-取代环己酮进行对映选择性去质子化”四面体字母。

D.Sato: Journal of American Chemical Society. 114. 761-763 (1992)

D.Sato：美国化学会杂志。

Yoshihiro hasegawa: "Control of Diastereoselectivity in the Alkylation of Chiral Lithium Enolates Mediated by a Chiral Secondary Amine Ligand." Tetrahedron Letters. 34. 1963-1966 (1993)

Yoshihiro hasekawa：“手性仲胺配体介导的手性锂烯醇化物烷基化中非对映选择性的控制。”

Daisaku Sato: "Crystallographic and Li-6 and N-15 NMR Studies of a Chiral Bidentate Lithium Amide" J.Am. Chem. Soc. 114. 761-763 (1992)

Daisaku Sato：“手性二齿氨基锂的晶体学和 Li-6 和 N-15 NMR 研究”J.Am.

T.Yasukata: "Enantioselective Protonaeion of Achiral Lithium Enolates Using a chiral Amine in the Presence of Lithiam Bromide" Tetrahedron:Asymmetry. 4. 35-38 (1993)

T.Yasukata：“在溴化锂存在下使用手性胺对非手性烯醇锂进行对映选择性质子化”四面体：不对称性。