Pinto Artur, Jia Yanxing, Neuville Luc, Zhu Jieping
Institut de Chimie des Substances Naturelles, CNRS, 91198 Gif-sur-Yvette Cedex, France.
Chemistry. 2007;13(3):961-7. doi: 10.1002/chem.200601016.
An efficient synthesis of functionalized 3-alkyl-3-cyanomethyl-2-oxindole 1 by a palladium-catalyzed domino Heck-cyanation reaction has been developed. Reaction of ortho-iodoanilide 5 with potassium ferro(II)cyanide, K(4)[Fe(CN)(6)], dissolved in DMF in the presence of palladium acetate and sodium carbonate afforded oxindole 1 in good to excellent yields. An enantioselective domino Heck-cyanation process has been developed for the first time using (S)-DIFLUORPHOS as a chiral supporting ligand, and an enantioselectivity of up to 79 % ee in the enantiomerically enriched oxindole was obtained under optimized conditions. A concise total synthesis of esermethole and physostigmine, powerful inhibitors of acetyl- and butyryl-cholinesterase, is documented.
已开发出一种通过钯催化的多米诺 Heck-氰化反应高效合成官能化 3-烷基-3-氰甲基-2-吲哚酮 1 的方法。邻碘苯胺 5 与溶解在 DMF 中的亚铁氰化钾 K(4)[Fe(CN)(6)] 在醋酸钯和碳酸钠存在下反应，以良好至优异的产率得到吲哚酮 1。首次使用 (S)-二氟膦作为手性辅助配体开发了对映选择性多米诺 Heck-氰化过程，在优化条件下，对映体富集的吲哚酮中的对映选择性高达 79% ee。记录了乙酰胆碱酯酶和丁酰胆碱酯酶的强效抑制剂依色甲醚和毒扁豆碱的简洁全合成。
