Quantum chemistry study on the reduction of prechiral ketone by sodium borohydride

The asymmetric reduction mechanism of p-methylcyclohexanone by sodium borohydride was investigated with ab initio calculations. Four-member ring and six-member ring mechanisms have been studied, both of which have three reaction paths with the main path through two-step transition state. The study shows that though four-member ring transition state mechanism without solvent participation could explain the reduction of p-methylcyclohexanone reasonably, the calculated ratio of enantiomers could not match the experimental result. The further study of the six-member ring mechanism with the participation of iso-propanol demonstrates that the calculated ratio of enantiomers agrees with the experimental results essentially. All above results show that the reaction experiences the six-member ring transition state with two-step path.