Does Confinement Always Lead to Thermodynamically and/or Kinetically Favorable Reactions? A Case Study using Diels–Alder Reactions within ExBox+4 and CB[7]

The impact of geometrical confinement on the thermodynamic as well as kinetic aspects of a model cycloaddition reaction between 1,3‐butadiene and ethylene have been investigated based on density functional theory calculations. To this end, organic hosts ExBox+4 and cucurbit[7]uril (CB[7]) were used to impose confinement effects on the reactants, transition state (TS), and product involved in the reaction. The results suggest that the shape of the host and thereby the nature of the confining regime dictates the thermodynamic outcome of the reaction. The reaction becomes thermodynamically more spontaneous inside CB[7] as compared with that in either ExBox+4 or in the “unconfined” gaseous state. Furthermore, the rate constant associated with the reaction increases manifold inside CB[7]. Atoms‐in a‐molecule, noncovalent interaction, natural bond orbital, as well as energy decomposition analyses suggest that the close geometrical proximity of the reactants inside CB[7] as well as extra stabilization of the TS in the encapsulated state may dictate the outcome. Forced to react: The cycloaddition reaction of 1,3‐butadiene and ethylene becomes thermodynamically and kinetically more favorable inside cucurbit[7]uril as compared with that inside ExBox+4 as well as in the unconfined state.