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

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. 2-甲氧基苯甲酸-2，6-二叔丁基-4-甲氧基苯酯与几种有机金属化合物反应，均生成甲氧基取代产物和/或苯甲酸环上的共轭加成产物，随着负碳离子给电子能力的增强，后者的生成优先于前者。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.以手性环番和缩醛为底物进行了S_NAr反应，实现了手性元素在C-中心手性、平面手性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

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