Regioselective Syntheses of Multisubstituted Aromatic Compounds via Ester-Mediated Nucleophilic Alkylation

通过酯介导的亲核烷基化区域选择性合成多取代芳香族化合物

• 批准号: 10555318
• 负责人: MIYANO Sotaro
• 金额: $ 8万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10555318/
• 关键词: Nucleopholic Aromatic Substitution; Chelation Control; Indanol; ternaphthalene; Michellamine; Larreantin; Blestriarene; Thiacalix[4]arene; ビフェナンスロール; チアカリックスアレーン; アミノチアカリックスアレーン; Grignard試薬; リチウムアミド; 共役付加反応; 軸不斉ターナフタレン; 光学活性インダノール; 多置換芳香族化

We have investigated regioselective syntheses of multisubstituted aromatic compounds via the ester-mediated nucleophilic aromatic substitution(S_NAr)and the conjugate addition to benzoate rings. 1.The S_NAr reaction of 2-methoxybenzoates with Grignard reagents was found to be accelerated by introduction of a methoxy or halo substituent at the 3-position of the benzoate ring. The ligating ability of the 3-methoxy group was found to play a crucial role in enhancing the reactivity of the 2-methoxy moiety, while the electron-withdrawing ability was more important in the case of the halogens. 2.A stepwise S_NAr reaction of 2, 6-dimethoxybenzoates with two kinds of Grignard reagents was achieved by controlling the molar equivalence of the Grignard reagents to the substrates, giving the corresponding benzoic esters with different substituents at the 2- and 6-positions. Novel chiral alcohols, 1, 8-disubstituted fluorenols and 7-substituted 2, 2-dimethyl-1-indanols were conveniently synthesized … More by using the process and evaluated for their chiral induction abilities. 3.Novel ternaphthalenes were synthesized by the S_NAr reaction between 1, 5-(or 1, 4-)dialkoxynaphthalen-2, 6-(or 2, 3-)dicarboxylic esters and 1-naphthyl Grignard reagents or 1-alkoxy-2-naphthoic esters and naphthalen-1, 4-di-Grignard reagents. 4.A regioselective allylation of 3-bromo-2, 6-dimethoxybenzonic ester at the 2-position was achieved and utilized for a facile preparation of 5-bromo-8-methoxy-3-methylnaphthalen-1-ol, which is a key compound for the syntheses of michellamines. 5.A combination of the estermediated S_NAr reaction and the conjugate addition to benzoate rings made it possible to introduce three different substituents at the 2-, 4- and 6-positions of a 3-bromo-2, 6-dimethoxybenzoate, which was utilized for the synthesis of a larreantin analog. 6.A biphenyl-2-carboxylic ester, which had been prepared by the S_NAr reaction, was successfully utilized as a key synthetic intermediate for blestriarene C.7.Calix[4]arenes comprised of four aniline units were synthesized for the first time via the S_NAr reaction of tetramethyl ether of sulfinyl- or sulfonylcalix[4]arene with lithium benzylamide. Less

本文研究了通过酯介导的芳香亲核取代反应（S_NAr）和苯甲酸环上的共轭加成反应区域选择性合成多取代芳香化合物。1.在苯甲酸环的3位引入甲氧基或卤代取代基可加速2-甲氧基苯甲酸酯与格氏试剂的S_NAr反应。发现3-甲氧基的配位能力在增强2-甲氧基部分的反应性方面起着至关重要的作用，而吸电子能力在卤素的情况下更重要。2.2，6-二甲氧基苯甲酸酯与两种Grignard试剂通过控制Grignard试剂与底物的摩尔当量，实现了逐步S_NAr反应，得到了相应的2-和6-位上具有不同取代基的苯甲酸酯。方便地合成了新型手性醇、1，8-二取代芴醇和7-取代2，2-二甲基-1-茚满醇 ...更多信息 并对它们的手性诱导能力进行了评价。3.通过1，5-（或1，4-）二烷氧基萘-2，6-（或2，3-）二甲酸酯与1-萘格氏试剂或1-烷氧基萘-2-甲酸酯与萘-1，4-二格氏试剂的S_NAr反应合成了新的三萘。4.通过3-溴-2，6-二甲氧基苯甲酸酯在2-位上的区域选择性烯丙基化反应，合成了一种新的化合物5-溴-8-甲氧基-3-甲基萘-1-醇。5.通过酯介导的S_NAr反应和苯甲酸环上的共轭加成反应，在3-溴-2，6-二甲氧基苯甲酸酯的2-、4-和6-位引入了三个不同的取代基，并将其用于合成larreantin类似物。6.通过S_NAr反应合成了联苯-2-羧酸酯，成功地将其作为合成杯[4]芳烃C的关键中间体。7.首次通过亚磺酰基杯[4]芳烃的四甲基醚与苄基氨基锂的S_NAr反应合成了由四个苯胺单元组成的杯[4]芳烃。少

项目成果

服部徹太郎 他: "Cationic palladium (II) complex-catalyzed [2+2] cycloaddition and tandem cycloaddition-allylic rearrangement of ketene with aldehydes : an improved synthesis of sorbic acid"Chem.Commun.. 2000・1. 73-74 (2000)

Tetaro Hattori等：“阳离子钯(II)络合物催化的烯酮与醛的[2+2]环加成和串联环加成-烯丙基重排：山梨酸的改进合成”Chem.Commun. 2000・1。 74 (2000)

H.Katagiri: "Calix[4]arenes Comprised of Aniline Units"J.Am.Chem.Soc.. 123. 779-780 (2001)

H.Katagiri：“由苯胺单元组成的 Calix[4] 芳烃”J.Am.Chem.Soc.. 123. 779-780 (2001)

M.Date: "Efficient 1,8- and 1,9-Asymmetric Inductions in the Grignard Reaction of δ- and ε-Keto Esters of 1,1'-Binaphthalen-2-ols Bearing an Oligoether Tether as the 2'-Substituent : Application to a Synthesis of (-)-Malyngolide"J.Chem.Soc., Perkin Trans.

M.Date：“带有寡醚系链作为 2-取代基的 1,1-联萘-2-醇的 δ-和 ε-酮酯格氏反应中的高效 1,8- 和 1,9-不对称诱导：在(-)-Malyngolide的合成中的应用”J.Chem.Soc.，Perkin Trans。

Y.Tamai: "Pseudo-Macrocyclic Chelation Control in Remote Asymmetric Induction. Highly Efficient 1, 7-Asymmetric Inductive Hydride Reduction and Grignard Reaction of γ-Keto Esters of 1, 1'-Binaphthalen-2-ols Bearing an Appropriate Oligoether Group as the 2

Y.Tamai：“远程不对称感应中的伪大环螯合控制。带有适当低聚醚基团的 1, 1-联萘-2-醇的 γ-酮酯的高效 1, 7-不对称感应氢化物还原和格氏反应2

T.Hattori: "Is the CD Exciton Chirality Method Applicable to Chiral 1,1'-Biphenanthryl Compounds?" J.Am.Chem.Soc.120(35). 9086-9087 (1998)

T.Hattori：“CD 激子手性方法是否适用于手性 1,1-联菲基化合物？”