Diels-Alder Reactions in Water are Determined by Microsolvation

TL;DR

This study uses ab initio molecular dynamics to show that microsolvation governs Diels-Alder reaction acceleration in water, with nanoconfinement not significantly altering the mechanism, implying other factors drive acceleration in microdroplets.

Contribution

It reveals that microsolvation of the dienophile's carbonyl group controls reaction acceleration, and nanoconfinement does not significantly change the mechanism, challenging assumptions about nanoconfinement effects.

Findings

Reaction acceleration is similar in bulk water and nanoconfined water.

Microsolvation stabilizes the transition state regardless of environment.

Acceleration in microdroplets likely arises from altered reaction environments, not microsolvation.

Abstract

Nanoconfined aqueous environments and the recent advent of accelerated chemistry in microdroplets are increasingly being investigated for catalysis. The mechanisms underlying the enhanced reactivity in alternate solvent environments, and whether the enhanced reactivity due to nanoconfinement is a universal phenomenon, are not fully understood. Here, we use ab initio molecular dynamics simulations to characterize the free energy of a retro-Diels-Alder reaction in bulk water at very different densities and in water nanoconfined by parallel graphene sheets. We find that the broadly different global solvation environments accelerate the reactions to a similar degree with respect to the gas phase reaction, with activation free energies that do not differ by more than kbT from each other. The reason for the same acceleration factor in the extremely different solvation environments is that it is the microsolvation of the dienophile's carbonyl group that governs the transition state stabilization and mechanism, which is not significantly disrupted by either the lower density in bulk water or the strong nanoconfinement conditions used here. Our results also suggest that significant acceleration of Diels Alder reactions in microdroplets or on-water conditions can't arise from local microsolvation when water is present, but instead must come from highly altered reaction environments that drastically change the reaction mechanisms.