THE TERTIARY AMIDE AS AN EFFECTIVE DIRECTOR OF ORTHO LITHIATION
THE TERTIARY AMIDE AS AN EFFECTIVE DIRECTOR OF ORTHO LITHIATION
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DOI：
10.1021/jo00340a008
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发表时间：
1982-01-01
影响因子：
3.6
通讯作者：
BROWN, RA
中科院分区：
文献类型：
--
作者：
BEAK, P;BROWN, RA
叔酰胺！ V，N-二乙基苯甲酰胺(1)和N，N，N-二异丙基苯甲酰胺(3)分别在-78℃下用仲丁基锂/TMEDA或正丁基锂/TMEDA处理得到邻位锂化物质2。1的锂化随后与甲基碘、乙基碘、二苯甲酮、丙酮、苯甲醛或三甲氧基硼烷-过氧化氢反应得到预期的邻位取代产物。邻位和对位取代的苯甲酰胺中二乙酰胺和氯、甲氧基、磺酰胺、（二甲氨基）甲基或恶唑啉官能团之间的分子内竞争使得叔酰胺基在规定条件下比任何非甲酰胺官能团更有效地引导金属化。间位取代的二乙基苯甲酰胺中的氯基和甲氧基观察到定向效应的互补性，但甲基则不然。发现仲酰胺的定向能力与仲丁基锂/TMEDA在THF中于78℃下的叔酰胺相当，尽管产率较低。 13C NMR 化学位移对于通过某些产物的内酯化化学确认的结构分配特别有用。用1V，N-二异丙基-2，6-二氘代苯甲酰胺进行的标记研究表明，3的邻位的锂化是直接的，而不是最初形成的氮杂阴离子重排的结果。举例说明了通过适当选择有机锂碱来控制邻位或苄位的金属化，例如N，N-二异丙基-对甲苯酰胺。注意到叔酰胺对于控制邻位锂化和区域特异性芳族取代的价值。通过去质子化形成区域特异性邻位金属化芳族化合物（如方案 I 中的取代苯所示）是一个具有合成价值和机械兴趣的反应。一个经典且具有开创性的案例是吉尔曼和维蒂格在 40 多年前报道了苯甲醚与正丁基锂反应生成 2-锂苯甲醚。 1 早期发展，最初由 Gilman 和 Hauser 进行
The tertiary amides! V, lV-diethylbenzamide (1) and JV, jV-diisopropylbenzamide (3) give the ortho-lithiated species 2 on treatment with sec-BuLi/TMEDA or n-BuLi/TMEDA, respectively, at-78 C. Lithiation of 1 followed by reaction with either methyl iodide, ethyl iodide, benzophenone, acetone, benzaldehyde, or trimethoxy-borane-hydrogen peroxide gives the expected ortho substituted product. Intramolecular competition between the diethylamide and chloro, methoxyl, sulfonamide,(dimethylamino) methyl, or oxazoline functions in orthoand para-substituted benzamides establishes the tertiary amido group to be more effective in directing metalation than any noncarboxamide functional group under the prescribed conditions. Complimentarity of directing effects is observed with the chloro and methoxyl groups in the meta-substituted diethylbenzamides but not with the methyl group. The secondary amide is found to have a directing ability comparable to the tertiary amide with sec-BuLi/TMEDA at-78 C in THF although the yields are low. 13C NMR chemical shifts are particularly useful for the structural assignments which are confirmed chemically by lactonization of some products. A labeling study with lV, JV-diisopropyl-2, 6-dideuteriobenzamide suggests that lithiation of the ortho positionof 3 is direct and not the resultof rearrangement of an initially formed-aza anion. Control of metalation at the ortho or benzylic position by proper selection of the organolithium base is illustrated for fVJV-diisopropyl-p-toluamide. The value of the tertiary amide for control of ortho lithiations and regiospecific aromatic substitutions is noted.The formation of regiospecifically ortho metalated aro-matics by deprotonation, illustrated for substituted benzenes in Scheme I, is a reaction of synthetic value and mechanistic interest. A classic and seminal case is the reaction of anisóle with n-butyllithium to give 2-lithio-anisole reported byGilman and by Wittig over 40 years ago. 1 Early developments, initially by Gilman and Hauser