Solvent Effects on the Selectivity of Ambimodal Dipolar/Diels-Alder Cycloadditions: A Study Using Explicit Solvation Models.

The reaction between 2-aminoacrolein and 1,3-butadiene serves as a representative example of post-transition state bifurcation (PTSB), leading to both Diels-Alder (4 + 2) six-membered and dipolar (4 + 3) seven-membered cycloaddition products via a single ambimodal transition state structure. Previous quantum chemical studies employing an implicit solvation model have highlighted the significant influence of polar solvents on the branching dynamics of this bifurcation, primarily due to the stabilization of charge-separated dipolar intermediates. Herein, the PTSB behavior is investigated in further detail using an explicit solvation model comprising up to 45 water molecules. Both static reaction path calculations and molecular dynamics simulations are carried out on water cluster models of selected sizes, employing the parameter-optimized semiempirical GFN2-xTB method, which accurately reproduces results obtained from density functional theory. The findings reveal that the PTSB dynamics are highly sensitive to the number of water molecules involved.