Creation of Novel Axially-Chiral Compounds : Developments toward Asymmetric Synthesis

新型轴向手性化合物的创造：不对称合成的进展

• 批准号: 06453189
• 负责人: FUJI Kaoru
• 金额: $ 4.74万
• 依托单位: KYOTO 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: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06453189/
• 关键词: Axial Chirality; Asymmetric Protonation; Asymmetric Olefination; 1,1'-Binaphthalene-2,2'-diol; 1,1'-Binaphthalene-8,8'-diol; Wittig Reaction; 軸不斉化合物; 不斉合成; Horner-Wadsworth-Emmons反応; エノレート; α-ジケトン; σ-対称; プロキラル

This research project has dealt with asymmetric synthesis using axially chiral compounds which possess 1,1'-binaphthalene skeleton. Especially, asymmetric Wittig reaction and asymmetric protonation were examined. Since Wittig reaction creates sp^2 carbon, its application to asymmetric synthesis had rather been limited. We demonstrated asymmetrization of sigma-symmetrical meso-compounds through discrimination of enantiotopic carbonyls of alpha-diketones. Using chiral phosphonates having 1,1'-binaphthalene-2,2'-diol moiety as a chiral auxiliary, highly enantioselective Wittig-type reactions were achieved with rigid cyclic alpha-diketones. Intramolecular Asymmetric Witting-type reactions were also performed to afford polycyclic ketones in moderate to high enantioselectivity.Since protonation is one of the most simple operations out of chemical transformations, asymmetric protonation of enolates should have wide variety of applications to production of optically active carbonyl compounds. We have investigated asymmetric protonation using chiral proton sources having 1,1'-binaphthalene-8,8'-diol moiety. Enantioselectivity of the protonation depended strongly on the countercation of the enolates. While the lithium enolate of an alpha-tetralone derivative gave the products of only 9% ee, the corresponding magnesium enolare afforded the product of 94% ee.

本研究计划主要是利用具有1，1 '-联萘骨架的轴向手性化合物进行不对称合成。重点考察了不对称Wittig反应和不对称质子化反应。由于维蒂希反应生成的是sp^2碳，因此它在不对称合成中的应用受到了限制。我们通过对α-二酮的对映羰基的鉴别证明了σ-对称内消旋化合物的不对称化。以含1，1 ′-联萘-2，2 ′-二醇的手性膦酸酯为手性助剂，实现了刚性环状α-二酮与手性膦酸酯的高对映选择性Wittig反应.分子内不对称Witting型反应也能以中到高的对映选择性得到多环酮.由于质子化是化学转化中最简单的操作之一，烯醇化物的不对称质子化在光学活性羰基化合物的制备中具有广泛的应用.我们研究了使用具有1，1 '-联萘-8，8'-二醇部分的手性质子源的不对称质子化。质子化的对映选择性强烈依赖于烯醇化物的抗衡阳离子。α-四氢萘酮衍生物的烯醇化锂得到的产物仅为9%ee，而相应的烯醇化镁得到的产物为94%ee。

项目成果

Fujie Tanaka: "1,1′-Binaphthalene-2,2′-diol as a Chiral Auxiliary. Diastereoselective Alkylation of Binaphthy1 Esters, Complex-Induced Proximity Effects in Enolate Formation, and One-Step Synthesis of an Optically Active β-Substituted Ketone" J. Am. chem.

Fujie Tanaka：“1,1-联萘-2,2-二醇作为手性助剂。联萘酯的非对映选择性烷基化、烯醇化物形成中络合物诱导的邻近效应以及光学活性 β-取代酮的一步合成“ J. Am. chem.

Fujie Tanaka: "1,1'-Binaphthalene-2,2'-diol as a Chiral Auxiliary Diastereoselective Alkylation of Binaphthyl Esters, Complex-Induced Proximity Effects in Enolate Formation, and One-Step Synthesis of an Optically Active -Substituted Ketone" J.Am.Chem.Soc.

Fujie Tanaka：“1,1-联萘-2,2-二醇作为联萘酯的手性辅助非对映选择性烷基化、烯醇化物形成中络合物诱导的邻近效应以及光学活性取代酮的一步合成”J

Kiyoshi Tanaka: "Asymmetric Michael Addition Reactions of Chiral Prop-2-enyl-and But-2-enylphosphonate Anions with Cyclic Enones" J. Org. Chem.,. 60. 8036-8043 (1995)

Kiyoshi Tanaka：“手性丙-2-烯基-和丁-2-烯基膦酸阴离子与环烯酮的不对称迈克尔加成反应”J. Org。

Kaoru Fuji: "Enantioselective Protonation of Enolates : Novel Chiral Proton Sources and Remarkable Effects of the Countercation" J.Org.Chem.60. 1914-1915 (1995)

Kaoru Fuji：“烯醇化物的对映选择性质子化：新颖的手性质子源和反阳离子的显着效果”J.Org.Chem.60。

Kaoru Fuji: "Enantioselective Protonation of Enolates:Novel Chiral Proton Sources and Remarkable Effects of the Counter Cation" J.Org.Chem.60. (1995)

Kaoru Fuji：“烯醇化物的对映选择性质子化：新型手性质子源和反阳离子的显着效应”J.Org.Chem.60。