Asymmetric electrochemical carboxylation of prochiral acetophenone: An efficient route to optically active atrolactic acid via selective fixation of carbon dioxide

A novel method of selective fixation of carbon dioxide was developed in this work. In an undivided cell the pharmaceutically active intermediate 2-hydroxy-2-phenylpropionic acid (atrolactic acid) has been produced from prochiral acetophenone in the presence of two kinds of chiral alkaloids, cinchonidine and cinchonine, acting as the inductors which were inclined to afford R and S products, respectively. Since the alkaloid has a strong tendency to adsorb to the surface of the cathode, three different cathode materials (stainless steel, platinum and copper) were applied in the process of asymmetric electrochemical carboxylation. Eventually, very distinct results were obtained. When the stainless steel was used as the cathode, a highest enantiomeric excess (ee) of 29.8% was achieved with an electrocarboxylation yield of 24.5%. Using cinchonidine and cinchonine as the inductors, the ee value of the aimed 2-hydroxy-2-phenylpropionic acid was also measured as a function of the concentration ratio of the alkaloid to the cocatalyst of butanol, supporting electrolyte, temperature, charge passed, current density and solvent. In particular, the butanol may play a critical role of helping to accomplish the asymmetric electrocarboxylation induction. From further analysis of cyclic voltammograms of acetophenone before and after addition of the alkaloid and butanol, a possible induction mechanism was put forward accordingly.