On the Role of Hydrogen Bond Strength and Charge Transfer in an On‐Water Diels–Alder Reaction: Semiempirical and Free Energy Calculations

On-water catalysis is widely exploited, yet the microscopic origin of rate enhancements at aqueous interfaces remains debated. In the spirit of the second-generation Car-Parrinello method, we use a modified Langevin-type scheme to accelerate density-functional based tight-binding molecular dynamics in order to investigate the free energy of two Diels-Alder reactions on-water: the cycloaddition of cyclopentadiene with ethyl cinnamate and that with ethyl thionocinnamate. The only difference between the two studied molecules is that the carbonyl oxygen of the cinnamate is a thiocarbonyl sulfur in the thionocinnamate; hence, the first is a strong and the second a weak hydrogen bond acceptor. The oxygen-containing dienophile reacts through an almost synchronous transition state with a barrier of ~13 kcal/mol, whereas the sulfur analogue follows an asynchronous pathway with a barrier of ~24 kcal/mol because a transient SC contact competes with CC bond formation. We find no increase in the number or strength of hydrogen bonds at the transition state. Instead, the catalytic role of the interface is to maintain an electronically productive hydrogen-bond environment that stabilizes charge reorganization along the reaction coordinate. These results indicate that, for the present on-water reactions, hydrogen-bond quality and charge-transfer capability are more decisive than the hydrogen-bond count alone.