An overview of modern approaches to palladium-catalyzed allylation and deacylative allylation of 3-acetyl-2-oxindoles with allylic alcohols

by Islambek

ABSTRACT

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Palladium plays a major part in catalysis of carbon-carbon bond formation at C-3 site of 2-oxindoles. Among C-C bond formation by palladium allylation is popular, especially allylation by carbonates and acetates generated from allyl alcohols, which have -OH being poor leaving group. During allylation process allyl-Pd intermediates are observed. Indeed, synthesis of alcohol derivatives is usually avoided due to cost and multiple steps. Therefore, allylic alcohol is usually purchased. There are versatile methodologies for palladium catalyzed allylation of oxindoles. First one is based on the Meerwein-Eschenmoser Claisen rearrangement of indoline-2-ones involving a transformation of 2-amino allyl vinyl ethers to γ,δ-unsaturated amides. First, 3-(1-Methoxyethenyl)-1H-indole is treated with NCS and 1,4-dimethyl- piperazine followed by Cl₃CCO₂H and 2-methyl- 2-propen-1-ol. After that resulting hemiaminal is added to L*Pd(SbF₆) in CH₂Cl₂, where L is ligand. BINAP, tol-BINAP and xyl-BINAP ligands give 48%, 47% and 50% yield respectively, while i-PrPHOX and t-BuPHOX give 79 and 89% yield. Second method is based on allylation of 3-acyl-indoline-2-ones with derivatives of esters and ketones. Here, MeCO₂-oxindole derivatives are converted into oxindole enolates after retro-condensation by allylic alcohol. Then, enolate reacts with Pd-π allyl complex to give allylic oxindole. 0.25 mmol (1 equivalent) of oxindole, 1.2 eq of NaH and 5 mol% of Pd(PPh3 )₄ are consumed to give 91% yield. Third method is Pd(OAc)2, triethylborane and 1,3-bis(diphenylphosphino)propane (dppp) catalyzed allylation of 3-acyl-2-oxindole with allyl alcohol that gives 99% yield of 3-acetyl-3-allyl-1-methyl-2-oxindole. Replacing dppp with rac-BINAP and Et₃B with rac-BINOL phosphoric acid and using Pd(OAc)₂ instead of Pd(dba)₂ gave monoallylated 2-oxindoles with 98% yield. Fourth method is a straight allylation of indoline-2-ones with non-active allyl alcohol in presence of Pd(OAc)2/Ph3P and benzoic acid. At 5 mol % of Pd(OAc)2, 5 mol % Ph3P and 5 mol % PhCO2H the yield is higher than 99%. Similar yield was obtained by catalytic presence of 5mol % of Pd(PPh3)4 and PhCO2H.