Solvation Effects Drive the Selectivity in Diels-Alder Reaction Under Hyperbaric Conditions

High pressure effects on the Diels-Alder reaction in condensed phase are investigated by means oftheoretical methods, employing advanced multiscale modeling approaches based on physically groundedmodels. The simulations reveal how the increase of pressure from 1 to 10000 atm does not affect thestability of the reaction products, modifying the kinetics of the process by lowering considerably thetransition state energy. The reaction profile at high pressure remarkably differs from that at 1 atm,showing a submerged TS and a pre–TS structure lower in energy. The different solvation between endoand exo pre–TS is revealed as the driving force pushing the reaction toward a much higher preferencefor the endo product at high pressure.