Synthesis of γ-keto carboxylic acids from γ-keto-α-chloro carboxylic acids via carbonylation—decarboxylation reactions catalysed by a palladium system

Abstract

A palladium-based catalytic system is highly active in the synthesis of γ-keto acids of type ArCOCH 2CH 2COOH via carbonylation-decarboxylation of the corresponding α-chloride. Typical reaction conditions are: P(CO) = 20–30 atm; substrate/H 2O/Pd = 100–400/800–1000/1 (mol); temperature: 100–110 °C; [Pd]=0.25 × 10 −2−1 × 1O −2 M; solvent: acetone; reaction time: 1–2 h. A palladium(II) complex can be used as catalyst precursor. Under the reaction conditions above, reduction of the precursor to palladium metal occurs to a variable extent. High catalytic activity is observed when the precursor undergoes extensive decomposition to the metal. Pd/C is also highly active. Slightly higher yields are obtainable when the catalytic system is used in combination with a ligand such as PPh 3. A mechanism for the catalytic cycle is proposed: (i) The starting keto chloride undergoes oxidative addition to reduced palladium with formation of a catalytic intermediate having a Pd-[CH(COOH)CH 2COPh] moiety. The reduced palladium may be the metal coordinated by other atoms of palladium and/or by carbon monoxide and/or by a PPh 3 ligand when catalysis is carried out in the presence of this ligand. It is also proposed that the keto group in the β-position with respect to the carbon atom bonded to chlorine weakens the CCl bond, easing the oxidative addition step and enhancing the activity of the catalyst. (ii) Carbon monoxide ‘inserts’ into the PdC bond of the above intermediate to give an acyl catalytic intermediate having a Pd-[COCH(COOH)CH 2COPh] moiety. (iii) Nucleophilic attack of H 2O to the carbon atom of the carbonyl group bonded to the metal of the acyl intermediate yields a malonic acid derivative as product intermediate. This, upon decarboxylation, gives the final product. Alternatively, the desired product may form without the malonic acid derivative intermediate, through the following reaction pathway: the acyl intermediate undergoes decarboxylation with formation of a different acyl intermediate, having a Pd-[CO-CH 2CH 2COPh] moiety, which, upon nucleophilic attack of H 2O on the carbon atom of the carbonyl group bonded to the metal, yields the final product.