Origins in the substituent effects in the aldol condensation of axially chiral thiohydantoins: a computational study

This study investigates aldol reactions between thiohydantoin derivatives and benzaldehyde, examining the substituent effects on the reaction mechanisms and reaction enantioselectivity. Agreement of calculations (M06-2X/6-311+G(d,p) / CPCM(THF)) with experiment suggests that the enantioselectivity is predominantly governed by thermodynamic control. Furthermore, distortion/interaction analysis elucidates the role of steric hindrance in determining product distributions.