Development and Application of Nucleophilic Aromatic Substitution Reaction Mediated by Unclassical Activating Groups

非经典活化基团介导的亲核芳香取代反应的开发与应用

• 批准号: 07555587
• 负责人: MIYANO Sotaro
• 金额: $ 1.66万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07555587/
• 关键词: Nucleophilic Aromatic Substitution; Conjugate Addition; Activating Group; ortho-Effect; Axially Chiral Binaphthyl; Triarylamine; Chiral Auxiliary; Chiral Aminophosphine; 芳香族求核置換反応; フルオレノール; インダノール; 共役付加; グリニャ-ル試薬; 有機リチウム試薬; アリル置換反応; キラルアセター

Although nucleophilic aromatic substitution reaction (S_NAr) is an important process in organic synthesis, it generally requires severe reaction conditions and/or the presence of highly electron-withdrawing, so-called "activating" groups on the aromatic nucleus, which limits its applicability. We have investigated the chelation-assisted S_NAr reaction mediated by unclassical activating groups and obtained the following results. 1.The reactions of 2,6-di-tert-butyl-4-methoxyphenyl 2-methoxybenzoate with several organometallics were found to give the methoxy-substitution products and/or the conjugate addition products to the benzoate ring, preferring the latter products at the expense of the former with the increase of the electron-donating ability of the carbanion species. 2.The S_NAr reactions were found to be accelerated by introducing a substituent which could ligate to the metal center of the nucleophiles into the 3-position of the benzoate ring. 3.Facile synthesis of O-methylhamati … More ne was achieved by the asymmetric biaryl coupling reaction of a chiral 1-menthoxy-2-naphthoate with an aryl Grignard reagent as the key step. 4.Chiral cyclophanes and an acetal were employed as the substrate of the S_NAr reaction and highly efficient conversions of chiral elements among C-centro-, planar and axial chirality were attained. 5.Triarylamines were conveniently prepared by the reaction of a 2- or 4-fluorobenzoate with lithium diarylamides. 6.Novel chiral alcohols, 1,8-disubstituted fluorenols and 7-substituted 2,2-dimethyl-1-indanols were synthesized via the S_NAr reaction and resolved. The latter were proved to be highly resistant to racemization and could effectively be utilized as chiral auxiliaries. 7.2-Sulfonyl-as well as 2-sulfinyl-substituted 1-methoxynaphthalenes were found to undergo the S_NAr reaction. Factors affecting the activating power of the 2-substituents were elucidated. 8.Chiral aminophosphines were prepared via the S_NAr reaction of 2-diphenylphosphinoyl-1-methoxynaphthalene with chiral lithium amides, followed by reduction of the phosphinoyl function. They could effectively be utilized as the ligands for palladium-catalyzed allylic substitution reaction. Less

虽然亲核芳香取代反应（S_NAr）是有机合成中的一个重要过程，但它通常需要苛刻的反应条件和/或在芳香核上存在高度吸电子的所谓“活化”基团，这限制了它的应用。本文研究了非经典活化基团介导的螯合辅助S_NAr反应，得到了以下结果。1.发现2-甲氧基苯甲酸2，6-二叔丁基-4-甲氧基苯基酯与几种有机金属化合物的反应会产生甲氧基取代产物和/或苯甲酸环的共轭加成产物，随着负碳离子物种给电子能力的增强，后者的选择性优先于前者。2.在苯甲酸环的3-位上引入一个能与亲核试剂金属中心连接的取代基，可加速S_NAr反应。3. O-甲基氨基甲酸酯的简易合成 ...更多信息 通过手性1-薄荷氧基-2-萘甲酸酯与芳基格氏试剂的不对称联芳基偶联反应，得到了一个新的手性化合物。4.以手性环番和乙缩醛作为S_NAr反应的底物，实现了手性元素在C-中心、平面和轴向手性之间的高效转化。5.通过2-或4-氟苯甲酸酯与二芳基氨基锂的反应方便地制备三芳基胺。6.通过S_NAr反应合成了1，8-二取代芴醇和7-取代2，2-二甲基-1-茚满醇等新型手性醇，并对其进行了拆分。后者被证明是高度抗外消旋化，可以有效地利用作为手性助剂。7.2-磺酰基和2-亚磺酰基取代的1-甲氧基萘都能发生S_NAr反应。阐明了影响2-取代基活化能力的因素。8.通过2-二苯基膦酰基-1-甲氧基萘与手性氨基锂的S_NAr反应，再还原膦酰基官能团，合成了手性氨基膦。它们可以有效地用作钯催化烯丙基取代反应的配体。少

项目成果

T. Hattori: "Synthesis of Chiral Aminophosphines via Nucleophilic Aromatic Substitution and Their Application to Palladium-Catalyzed Enantioselective Allylic Substitution" Enantiomer. 2(印刷中). (1997)

T. Hattori：“通过亲核芳香取代合成手性氨基膦及其在钯催化对映选择性烯丙基取代中的应用”对映体 2（出版中）。

T.Hattori: "Chelation-Assisted Nucleophilic Aromatic Substitution of 2-Sulfonyl-Substituted 1-Methoxynaphthalenes by Grignard Reagents : Factors Determining the Activating Ability of the 2-Sulfonyl Substituents." J.Chem.Soc., Perkin Trans.1. 1997-8. 1117-

T.Hattori：“格氏试剂对 2-磺酰基取代的 1-甲氧基萘进行螯合辅助亲核芳香取代：决定 2-磺酰基取代基活化能力的因素。”

T.Hattori: "Practical Synthesis of 4, -Methylbiphenyl-2-carboxylic Acid." Synthesis. 1995-1. 41-43 (1995)

T.Hattori：“4, -甲基联苯-2-羧酸的实际合成”。

N.Koike: "Ester-Mediated Nucleophilic Aromatic Substitution of 2,3-Alkylidenedioxybenzoic Esters by Aryl Lithium Reagents" Chem.Lett.1997-7. 641-642 (1997)

N.Koike：“通过芳基锂试剂对 2,3-亚烷基二氧基苯甲酸酯进行酯介导的亲核芳香取代”Chem.Lett.1997-7。

T.Hattori: "Chelation-assisted nucleophilic aromatic substitution of 2-sulfonyl-substituted 1-methoxynaphthalenes by Grignard reagents:factors determining the activating ability of the 2-sulfonyl substiuents" J.Chem.Soc.,Perkin Trans.1. 1997(8). 1117-1123

T.Hattori：“通过格氏试剂对 2-磺酰基取代的 1-甲氧基萘进行螯合辅助亲核芳族取代：决定 2-磺酰基取代基活化能力的因素”J.Chem.Soc.，Perkin Trans.1。