Solvation effects drive the selectivity in Diels–Alder reaction under hyperbaric conditions

Abstract

High pressure effects on the Diels–Alder reaction in condensed phase are investigated by means of theoretical methods, employing advanced multiscale modeling approaches based on physically grounded models.

High‐Pressure Reaction Profiles and Activation Volumes of 1,3‐Cyclohexadiene Dimerizations Computed by the Extreme Pressure‐Polarizable Continuum Model (XP‐PCM)

“…are performed to obtain reaction profiles at high pressures and activation volumes. Due to the large size of the system using a simulation box, the MD simulations were usually done with force fields, as illustrated in the works from the Weinberg group, [46–49] or by a hybrid quantum mechanics/molecular mechanics (QM/MM) approach, as shown in the work by Plotnikov and Martinez [50] and a recent work by Loco et al [51] …”

High-pressure reaction profiles and activation volumes of 1,3-cyclohexadiene dimerizations computed by the extreme pressure-polarizable continuum model (XP-PCM)

“…al. 50 The minimum is very shallow at low pressures (may be difficult to see in the figure, but it is there) but becomes apparent at 5.7 GPa. This minimum also shifts towards the TS as the pressure increases.…”

“…Molecular dynamics (MD) simulations or Monte Carlo simulations (an early example by Klärner et al 25 ) are performed to obtain reaction profiles at high pressures and activation volumes. Due to the large size of the system using a simulation box, the MD simulations were usually done with force fields, as illustrated in the works from the Weinberg group, 45,46,47,48 or by a hybrid quantum mechanics/molecular mechanics (QM/MM) approach, as shown in the work by Plotnikov and Martinez 49 and a recent work by Loco et al 50 We now report a thorough consideration of the potential energy surface (PES) of the thermal dimerization 1,3-cyclohexadiene, including [4+2]-ene pathways that were not considered previously. In addition, we report, for the first time, XP-PCM calculations on the activation volumes for the various dimerization reactions of 1,3-cyclohexadiene, offering a new approach for computationally studying the competing mechanisms of this reaction.…”

Hyperbaric reactions in organic synthesis. Progress from 2006 to 2021

“…High pressure is advantageous for reactions with sufficient negative changes in the activation volume (often referred to as ΔV ≠ ) which is defined as the difference in molar volumes between the transition state (TS) and the reacting substrates (IR) ΔV ≠ = V ≠ TS − ∑V IR , and can be either calculated theoretically [15][16][17] (and the references therein) or determined experimentally. 18,19 Such reactions can be divided into two main types: (a) combining two or more molecules (e.g.…”