  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.
