Palladium-catalyzed enantioselective domino heck-cyanation sequence: development and application to the total synthesis of esermethole and physostigmine.
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.
Pinto
Artur
A
Institut de Chimie des Substances Naturelles, CNRS, 91198 Gif-sur-Yvette Cedex, France.
Jia
Yanxing
Y
Neuville
Luc
L
Zhu
Jieping
J
D002384:Catalysis; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry*; D010830:Physostigmine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D009570:Nitriles; D009942:Organometallic Compounds; C518152:esermethole; D010165:Palladium; D010830:Physostigmine