Catalytic Asymmetric Synthesis of Functional Chiral Molucules

功能手性分子的催化不对称合成

• 批准号: 05453181
• 负责人: TOMIOKA Kiyoshi
• 金额: $ 4.8万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 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
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05453181/
• 关键词: Asymmetric synthesis; Chiral catalyst; Organolithiums; Chiral diether; Anino ether; beta-Lactam; Imines; Conjugate addition; 機能性キラル分子; 不斉合成; 不斉触媒; キラルエーテル; アミン; 触媒反応

Asymmetric synthesis of chiral molucules of excellent function in a large scale is one of the most important challenges in recent synthetic chemistry. For this purpose, design of a novel catalytic cycle and chiral catalyst is essential. We have found that catalytic chiral diether and amino ether promte the reaction of organolithiums in nonpolar medium. The activation is caused by deaggregation of organolithiums by these donor catalysts. This concept was extended to quite promising reactions as shown below.1. Catalytic asymmetric synthesis of beta-lactam of high ee by the reaction of lithium ester enolate with imine in the presence of 5 mol% chiral amino ether catalyst.2. Catalytic asymmetric synthesis of anines of more than 90% ee by the reaction of organolithium with imines.3. Catalytic asymmetric conjugate reaction of organolithiums to alpha, beta-unsaturated esters was performed in high ee in the presence of chiral diether catalyst.

大规模不对称合成功能优异的手性分子是当前合成化学的重要挑战之一。为此，设计一种新型的催化循环和手性催化剂是必不可少的。我们发现，在非极性介质中，催化剂手性二醚和氨基醚促进了有机锂的反应。活化是由这些供体催化剂引起的有机锂的解聚引起的。这个概念被扩展到非常有希望的反应，如下所示。在5mol%手性氨基醚催化剂存在下，烯醇化锂酯与亚胺反应催化不对称合成高ee值β-内酰胺.有机锂与亚胺反应催化不对称合成了ee值大于90%的苯胺.在手性二醚催化剂存在下，有机锂催化不对称共轭合成α，β-不饱和酯的反应在高ee值下进行。

项目成果

Isao Inoue, Mitsuru Shindo, Kenji Koga, and Kiyoshi Tomioka: "Steric Tuning in Chiral Ligand Mediated Enantioselective Alkylation of Imines." Tetahedron : Asymmetry. 4. 1603-1606 (1993)

Isao Inoue、Mitsuru Shindo、Kenji Koga 和 Kiyoshi Tomioka：“手性配体介导的亚胺对映选择性烷基化的空间调节”。

Motomu Kanai, Kenji Koga, and Kiyoshi Tomioka: "Solvent Effect and NMR Behavior in a Chiral Amidophosphine Mediated Reaction of Organocuprate with Chalcone." J.Chem.Soc., Chem.Commun.1248-1249 (1993)

Motomu Kanai、Kenji Koga 和 Kiyoshi Tomioka：“有机铜酸盐与查耳酮介导的手性氨基膦反应中的溶剂效应和 NMR 行为”。

Kazumasa Aoki, Makoto Nakajima, Kiyoshi Tomioka, and Kenji Koga: "Reinvestigation of Optical Purities of Optically Active Trimethylsilyl Enol Ethers of 4-Substituted Cyclohexanones." Chem.Pharm.Bull.41. 994-996 (1993)

Kazumasa Aoki、Makoto Nakajima、Kiyoshi Tomioka 和 Kenji Koga：“4-取代环己酮光学活性三甲基硅烯醇醚光学纯度的重新研究”。

K.Tomioka et al: "Asymmetric Addition of Aryllithiums to Naphthalene BHA-Esters Catalyzed by a Chiral Ligand" Tetrahedron Letters. 34. 681-682 (1993)

K.Tomioka 等人：“手性配体催化芳基锂与萘 BHA 酯的不对称加成”四面体快报。

K.Ando et al: "Asymmetric Alkylation of α-alkyl β-Keto Esters to α,α-Alkyl β-Keto Esters Having(R)-or(S)-Chiral Quaternary Center Depending on the Solvent System" Tetrahedron. 49. 1579-1588 (1993)

K.Ando 等人：“根据溶剂系统将 α-烷基 β-酮酯不对称烷基化为具有 (R)-或 (S)-手性季中心的 α,α-烷基 β-酮酯”四面体 49。 1579-1588 (1993)