Efficient synthesis of γ-oxo carboxylic esters and isotope-labeled 5-aminolevulinic acid (5-ALA) by Pd(OAc)2/phosphonium tetrafluoroborates catalyzed Fukuyama coupling reaction

Pd(OAc)2/phosphonium tetrafluoroborates efficiently catalyzed Fukuyama coupling reaction with p-tolyl thioesters and 3-ethoxy-3-oxopropylzinc bromide which provide γ-oxo carboxylic esters under mild conditions. Pd(OAc)2/PCy3·HBF4 is the most effective catalyst and provides a direct method for synthesizing functionalized γ-oxo esters with high efficiency from readily accessible carboxylic acids as starting materials. By utilizing the optimized conditions, isotope-labeled 5-aminolevulinic acid ((15N)-5-ALA) was efficiently synthesized.