Catalytic oxidation of α-substituted cyclohexanone with steric hindrance to 6-oxohexanoic acid involved during the total synthesis of (+)-biotin

Abstract

A homogeneous catalyst system FeCl3/DMSO was developed to catalyze α-substituted cyclohexanone to corresponding 6-oxohexanoic acid, an important intermediate involved during the synthesis of (+)-biotin. A highly efficient oxidation with 95.3 % of conversion and 88.0 % of selectivity was achieved using oxygen as the oxidant, which shows great advantage over the traditional peroxide method from industrial aspects. The detailed reaction process was evaluated to determine the parallel reactions scheme consisted by two oxidative reactions and one chlorination reaction. The [Fe(DMSO)4Cl2]Cl complex detected by UV–vis and FT-IR spectrometer was proposed as the active component during the catalytic process. The control experiments, capture of important intermediates, and kinetic study were performed, which showed the oxidation proceeded via the combination of ionic and radical pathway. The FeCl3/DMSO can be recycled with minor yield loss.