Preparation and Application of Solid, Salt-Stabilized Zinc Amide Enolates with Enhanced Air and Moisture Stability
Preparation and Application of Solid, Salt-Stabilized Zinc Amide Enolates with Enhanced Air and Moisture Stability
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DOI：
10.1002/anie.201700216
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发表时间：
2017-04-10
影响因子：
16.6
通讯作者：
Knochel, Paul
中科院分区：
文献类型：
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作者：
Chen, Yi-Hung;Ellwart, Mario;Knochel, Paul
在25 ℃下，在THF中用TMPZnCl中心点LiCl（TMP= 2，2，6，6-四甲基哌啶基）和Mg（OPiv）（2）处理各种N-吗啉代酰胺，提供了在溶剂蒸发后具有增强的空气和水分稳定性（在空气中的t（1/2）：1-3 h）的固体烯醇化锌。这些烯醇化物与（杂）芳基溴以及烯丙基和苄基卤进行钯催化和铜催化交叉偶联。以LaCl_3中心点2 LiCl为催化剂，芳基化N-吗啉代酰胺与格氏试剂发生酰化反应，生成各种酮。新的固体烯醇化物用于制备有效的抗乳腺癌候选药物，共六步，总产率为23%。
The treatment of various N-morpholino amides with TMPZnCl center dot LiCl (TMP= 2,2,6,6-tetramethylpiperidyl) and Mg(OPiv)(2) in THF at 25 degrees C provides solid zinc enolates with enhanced air and moisture stability (t(1/2) in air: 1-3 h) after solvent evaporation. These enolates undergo Pd-and Cucatalyzed cross-couplings with (hetero) aryl bromides as well as allylic and benzylic halides. The arylated N-morpholino amides were converted into various ketones by LaCl3 center dot 2 LiCl mediated acylation with Grignard reagents. The new, solid enolates were used to prepare a potent anti-breast-cancer drug candidate in six steps and 23% overall yield.