The Ess et al. work focused on the activation energies and didn't deal with the activation volumes of the reaction. Theoretical calculations of ∆𝑉 ‡ , especially from firstprinciples, have been a challenge. A simple and intuitive way to compute ∆𝑉 ‡ is to calculate the difference in van der Waals (vdW) volumes of the molecule at the reactant and transition states. The vdW volume is the volume of interlocking vdW spheres (often with scaled vdW radii) centered on the constituting atoms of the molecule. However, likely due to the negligence of intermolecular interactions and solvent effect, ∆𝑉 ‡ computed by this method are always too small in magnitude. An empirical packing coefficient was introduced to account for such negligence and to correct the underestimated ∆𝑉 ‡ , computed by this method. A new method for more rigorous ∆𝑉 ‡ calculations is the recently-developed extreme pressure polarizable continuum model (XP-PCM). As an extension of the popular polarizable continuum model (PCM) that tackles molecular solution energies at the standard condition of pressure, the XP-PCM allows for quantum chemical calculations of the energy profiles of chemical reactions under pressure. The effect of the pressure is introduced in XP-PCM via a repulsive interaction between the reactive molecular system and the surrounding solvent medium. Within XP-PCM, ∆𝑉 ‡ can be computed, according to the transition state theory, as the derivative of activation free energy with respect to pressure. The XP-PCM method has been applied to the calculations of the energy profiles of a subset of pericyclic reactions. Interesting phenomena such as a shift of the transition state and a switch of the rate determining step have been discovered by the calculations. Furthermore, the computed ∆𝑉 ‡ are in reasonable agreement with experimental value. Recent work by Fukuda and Nakatani applied the XP-PCM method to a retrocycloaddition. The necessary details of the physical basis and computational protocol of the XP-PCM method are given in the Computational Methodology section. In additional to reaction profiles, the XP-PCM method has also been applied to the studies of the effect of pressure on a variety of molecular properties, such as equilibrium geometries, vibrational frequencies, electronic excitation energies. We note here relevant approaches derived from the mechanochemistry field for high-pressure calculations on molecules and reactions. Notably, the recent GOSTSHYP method from the Stauch group 44 is capable of calculating activation volumes of reactions. Another approach for simulating high-pressure organic reactions employs a simulation box with periodic boundary condition, filled with solvated reactant molecules.