Sampling of Transition States for Predicting Diastereoselectivity Using Automated Search Method-Aqueous Lanthanide-Catalyzed Mukaiyama Aldol Reaction.

To predict the stereoselectivity of large and flexible reaction systems, structural sampling of many transition states (TSs) is required. We used an automated search method, the artificial force induced reaction (AFIR) method, for TS sampling and found 91 syn- and 73 anti-TSs for the diastereoselective C-C bond formation step of the aqueous lanthanide-catalyzed Mukaiyama aldol reaction. Among them 11 syn- and six anti-TSs are found to contribute significantly to the diastereomeric ratio at room temperature.