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 by a palladium-catalyzed domino Heck-cyanation reaction has been developed. Reaction of ortho-iodoanilide with potassium ferro(II)cyanide in the presence of palladium acetate and sodium carbonate afforded oxindole derivs., e.g., I, 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 (II, R = Me) and (+-)-physostigmine (II, R = CONHMe), powerful inhibitors of acetyl- and butyryl-cholinesterase, is also described. [on SciFinder (R)]


Published in:
Chemistry--A European Journal, 13, 3, 961-967
Year:
2007
Keywords:
Note:
CAN 146:337762
28-2
Heterocyclic Compounds (More Than One Hetero Atom)
Institut de Chimie des Substances Naturelles,CNRS,Gif-sur-Yvette,Fr.
Journal
0947-6539
written in English.
3375-31-3 (Palladium diacetate) Role: CAT (Catalyst use), USES (Uses) (prepn. of oxindole derivs. via palladium-catalyzed intramol. Heck-cyanation of N-aryl acrylamides in presence of potassium ferrocyanide); 13943-58-3 (Potassium ferrocyanide); 102804-50-2; 122128-46-5; 154386-63-7; 929610-20-8; 929610-21-9; 929610-22-0; 929610-23-1; 929610-24-2; 929610-25-3; 929610-26-4; 929610-27-5; 929610-28-6 Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of oxindole derivs. via palladium-catalyzed intramol. Heck-cyanation of N-aryl acrylamides in presence of potassium ferrocyanide); 34944-03-1P; 136977-64-5P; 136977-87-2P; 176327-11-0P; 929610-29-7P; 929610-30-0P; 929610-31-1P; 929610-32-2P; 929610-33-3P; 929610-34-4P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of oxindole derivs. via palladium-catalyzed intramol. Heck-cyanation of N-aryl acrylamides in presence of potassium ferrocyanide); 920-46-7; 18342-66-0; 191348-14-8 Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of physostigmine via amidation of iodo(methoxy)aniline with metharyloyl chloride followed by methylation, palladium-catalyzed Heck-cyanation, reductive amination/cyclization, methylation, demethylation and esterification); 2291-51-2P; 46479-71-4P; 65131-82-0P ((+-)-Esermethole); 70354-71-1P; 929610-35-5P; 929610-36-6P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of physostigmine via amidation of iodo(methoxy)aniline with metharyloyl chloride followed by methylation, palladium-catalyzed Heck-cyanation, reductive amination/cyclization, methylation, demethylation and esterification); 69926-97-2P ((+-)-Physostigmine) Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of physostigmine via amidation of iodo(methoxy)aniline with metharyloyl chloride followed by methylation, palladium-catalyzed Heck-cyanation, reductive amination/cyclization, methylation, demethylation and esterification); 32005-36-0 (Bis(dibenzylideneacetone)palladium); 445467-61-8; 503538-70-3 Role: CAT (Catalyst use), USES (Uses) (stereoselective prepn. of oxindole derivs. via palladium-phosphine-catalyzed asym. intramol. Heck-cyanation of N-aryl acrylamides in presence of potassium ferrocyanide); 131101-13-8P; 132620-31-6P; 685089-46-7P; 929610-37-7P Role: SPN (Synthetic preparation), PREP (Preparation) (stereoselective prepn. of oxindole derivs. via palladium-phosphine-catalyzed asym. intramol. Heck-cyanation of N-aryl acrylamides in presence of potassium ferrocyanide)
Laboratories:




 Record created 2010-11-25, last modified 2018-09-13


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