DEVELOPMENT OF HIGHLY CHEMOSELECTIVE DEPROTONATION USING ZINCATES

使用锌酸盐开发高化学选择性去质子化

• 批准号: 12672047
• 负责人: KONDO Yoshinori
• 金额: $ 2.18万
• 依托单位: TOHOKU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672047/
• 关键词: ORGANOZINCATES; DEPROTONATION; HYDROGEN-ZINC EXCHANGE REACTION; AROMATIC COMPOUNDS; NITROGEN HETEROAROMATICS; a-METALATION; REGIO SELECTIVITY; CARBON-CARBON BOND FORMATION; 含窒素芳香複素環・; α-メタル化; 炭素-炭素結合生成; 含窒素芳香複素環; パラジウム触媒; 化学選択的側鎖導入

As a new chemoselective deprotonative agent, TMP-zincate was designed. The agent was found to be easily prepared using LTMP and di-tert-butylzinc. The agent is stable ate complex and can be used for the selective metalation of functionalized aromatic compounds with electrophilic groups. Various electrophiles were reacted with the arylzincates prepared by this deprotonation, and the scope and limitation of the methodology was disclosed. The reaction was successfully applied for the deprotonation of heteroaromatic compounds such as pyridines, isoquinolines, quinolines, and other nitrogen heteroaromatics. On the metalation of substituted pyridines, unique regioselectivity was observed and a-metalation predominates when 2-halopyridines were employed for substrates. Further investigations on the origin of this regioselectivity are underway. Application of the deprotonation for solid phase synthesis was also investigated, and the possibility was examined although further optimization of reaction conditions are necessary. Relating the deprotonation, mesityllithium was found to be an another option for selective deprotonation on polymer support, and the investigation for the scope and limitation are underway.

设计了一种新型的化学选择性去质子剂TMP-锌酸盐。发现该试剂容易使用LTMP和二叔丁基锌制备。该试剂是稳定的络合物，可用于含亲电基团的功能化芳香族化合物的选择性金属化。用该方法制备的芳基锌酸酯与各种亲电试剂进行了反应，并对该方法的适用范围和局限性进行了讨论。该反应已成功应用于吡啶、异喹啉、喹啉等含氮杂环化合物的脱质子化反应。在取代吡啶的金属化反应中，观察到了独特的区域选择性，当以2-卤代吡啶为底物时，α-金属化占主导地位。对这种区域选择性的起源的进一步调查正在进行中。本文还研究了去质子化反应在固相合成中的应用，考察了其可能性，但还需进一步优化反应条件。与去质子化有关，均三甲苯基锂被认为是聚合物载体上选择性去质子化的另一种选择，其范围和局限性的研究正在进行中。

项目成果

Shilai, M., Uchiyama, M., Kondo, Y., Sakamoto, T.: "Preparation and Reaction of Pyridinyl Tellurides"J. Heterocyclic Chem.. 38. 481-484 (2001)

Shilai, M.、Uchiyama, M.、Kondo, Y.、Sakamoto, T.：“吡啶基碲化物的制备和反应”J。

M.Shilai,Y.Kondo,T.Sakamoto: "Selective Metallation of Thiophene and Thiazole Rings with Magnesium Amide Base"J.Chem.Soc.,Perkin Trans.1. 442-444 (2001)

M.Shilai，Y.Kondo，T.Sakamoto：“噻吩和噻唑环与氨基镁基的选择性金属化”J.Chem.Soc.，Perkin Trans.1。

Shilai, M., Uchiyama, M., Kondo, Y., Sakamoto, T.: "Preparation and Reaction of Pyridingl Tellurides"J. Heterocyclic Clom. 38. 481-484 (2001)

Shilai, M.、Uchiyama, M.、Kondo, Y.、Sakamoto, T.：“吡啶基碲化物的制备和反应”J。

Imahori, T., Uchiyama, M., Kondo, Y., Sakamoto, T.: "Regiocontrolled cleprotonative-zincation of bromopyvidines using aminozincates"Chem. Commun. 2450-2451 (2001)

Imahori, T.、Uchiyama, M.、Kondo, Y.、Sakamoto, T.：“使用氨基锌酸盐对溴吡啶进行区域控制的质子锌化”Chem。

Shilai, M., Kondo, Y., Sakamoto, T.: "Selective metalation of thiophene and thiazole rings with magnesium amide base"J. Chem. Soc., Perkin Trans.. 1. 422-444 (2001)

Shilai, M.、Kondo, Y.、Sakamoto, T.：“用酰胺镁碱选择性金属化噻吩和噻唑环”J。