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.

大规模不对称合成具有优异功能的手性分子是近年来合成化学中最重要的挑战之一。为此，设计新型催化循环和手性催化剂至关重要。我们发现催化手性二醚和氨基醚促进有机锂在非极性介质中的反应。活化是由这些供体催化剂对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。1。 5 mol%手性氨基醚催化剂存在下，烯醇锂酯与亚胺反应不对称催化合成高ee的β-内酰胺。 2．有机锂与亚胺反应不对称催化合成90%以上的胺。 3．在手性二醚催化剂存在下，在高ee下进行有机锂与α，β-不饱和酯的催化不对称共轭反应。

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)