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

## TL;DR

This study explores how water molecules affect the outcome of a chemical reaction involving 2-aminoacrolein and 1,3-butadiene, showing that solvent size strongly influences the reaction's product distribution.

## Contribution

The study introduces explicit solvation models with up to 45 water molecules to analyze solvent effects on ambimodal reaction pathways.

## Key findings

- The number of water molecules significantly affects the branching dynamics of the post-transition state bifurcation.
- GFN2-xTB simulations accurately reproduce the solvent effects observed in density functional theory calculations.
- Solvent size influences the formation of both (4 + 2) and (4 + 3) cycloadducts via a single transition state.

## Abstract

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.

Post‐transition state bifurcation in the reaction of 2‐aminoacrolein with 1,3‐butadiene is investigated using explicit solvation (up to 45 water molecules). GFN2‐xTB dynamics reveal strong solvent‐size effects on branching to (4 + 2) and (4 + 3) cycloadducts via an ambimodal transition state.© 2025 WILEY‐VCH GmbH