Ludwig-Maximilians-Universität München, Department Chemie, Butenandtstrasse 5-13, Haus F, 81377, München, Germany.
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto, 606-8502, Japan.
Angew Chem Int Ed Engl. 2017 Apr 10;56(16):4612-4616. doi: 10.1002/anie.201700216. Epub 2017 Mar 22.
The treatment of various N-morpholino amides with TMPZnCl⋅LiCl (TMP=2,2,6,6-tetramethylpiperidyl) and Mg(OPiv) in THF at 25 °C provides solid zinc enolates with enhanced air and moisture stability (t in air: 1-3 h) after solvent evaporation. These enolates undergo Pd- and Cu-catalyzed cross-couplings with (hetero)aryl bromides as well as allylic and benzylic halides. The arylated N-morpholino amides were converted into various ketones by LaCl ⋅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.
用 TMPZnCl⋅LiCl（TMP=2,2,6,6-四甲基哌啶）和 Mg(OPiv) 在 THF 中处理各种 N-吗啉酰胺，然后在 25°C 下蒸发溶剂，得到具有增强的空气和水分稳定性的固体锌烯醇盐（t 在空气中：1-3 h）。这些烯醇盐在 Pd 和 Cu 催化下与（杂）芳基溴化物以及烯丙基和苄基卤化物发生交叉偶联。用 LaCl ⋅2 ⁇ LiCl 介导的格氏试剂酰化反应，将芳基化的 N-吗啉酰胺转化为各种酮。新的固体烯醇盐用于通过六步反应和 23%的总收率制备一种有效的抗乳腺癌候选药物。
