Substituent effects on the reduction of 2-OMe, 2-SMe and 2-SeMe cyclohexanones by LiAlH4: An investigation of conformational equilibrium and transition states

Transition state (TS) structures for the reduction of 2-methoxy, 2-methylthio, and 2-methylselenocyclohexanone by LiAlH4 were optimized by density functional theory (B3LYP/6-31G(d,p)). Four transition state structures corresponding to the axial and equatorial attacks by LiAlH4 were located for each ketone conformer. Electronic potential maps were used to investigate the electronic effect of the substituent group on the stabilization of transition states (TS). Furthermore, it was analyzed the uneven carbonyl orbital distribution in LUMO (π*). Reduction stereoselectivity showed to be dependent on both ketone conformational ratio and reaction transition state.