Synthesis of γ-ketocarboxylic acids via reduction of γ-keto-α-hydroxycarboxylic acids with carbon monoxide catalyzed by a PdHCl system

A PdHCl catalytic system is highly active in the synthesis of γ-ketoacids of type ArCOCH2CH2COOH via reduction with CO of the ketohydroxy acids ArCOCH2CHOHCOOH. Typical reaction conditions are: PCO: 20-30 atm; Pd/ substrate/H2O/HCl = 1/400-1000/800-3000/ 100-1000 (mol); temperature: 100-110°C; [Pd]: 10-3 to 10-2 M; solvent: dioxane; reaction time: 1-2 h. The reaction occurs in high yield only when the palladium precursor is used in combination with HCl and in the presence of H2O. Under the reaction conditions employed, the palladium(II) complex used as catalyst precursor decomposes to palladium metal. Pd/C is also highly active. It is proposed that the catalytic cycle proceeds through the following steps: (i) The chloride ArCOCH2CHClCOOH, which forms in situ from the starting substrate and HCl, undergoes oxidative addition to reduced palladium with formation of a catalytic intermediate having a Pd-[CH(COOH)CH2COPh] moiety. (ii) Interaction of H2O and CO on the metal yields an intermediate having also a carbohydroxy ligand, (HOOC)-Pd-[CH(COOH)CH2COPh]. (iii) This intermediate, after β-hydride abstraction from the carbohydroxy ligand, gives off CO2 and reductive elimination gives product PhCOCH2CH2COOH. Alternatively, HCl may react with the intermediate proposed in step (i), yielding directly the product and a Pd(II) species, which is reduced by CO to a Pd(0) species, which starts another catalytic cycle. © 1994.