Peering into the Darkness: Quantum Chemistry Shines a Light on Reaction Mechanisms in the Gas-phase and in Solution

Computational chemistry has continued to advance allowing for more complex investigations into larger systems. A challenge remains the way that solvent should be accounted for in a system. Implicit solvent corrections are quick and can easily be added to a computational method when needed. However, solvents can play a more direct role in a reaction through hydrogen-bonding or by acting as a solvent catalyst. This involvement requires including the bulk solvent in calculations, which is not possible with standard QM methodologies. Addition of explicit solvent molecules requires careful consideration of the position and number of solvent molecules. Three mechanistic investigations are presented here, all involving a different treatment to model the system accurately. First, the barriers for the abstraction of hydrogen atoms on 1-butyl-3-methylimidazolium by an F atom were determined. The reactions were carried out in vacuuo, and as such, a gas-phase DFT model was enough to accurately describe the system. Secondly, a phosphoramidate reaction of [Cp*Ir(κ2-N,O-Xyl(N)P(O)(OMe)2][BArF4] with propyne was modelled in dichloromethane. No direct solvent involvement was identified during the experiment and robust experimental data confirmed that implicit solvent corrections accounting for dichloromethane were needed. Finally, two Diels-Alder reactions were modelled that were involved in the synthesis of methoxatin. The experimental results indicated a strong solvent effect, showing only significant yields in HFIP and TFE. Implicit solvent corrections did not determine the origin of this solvent effect. The inclusion of at least one explicit solvent molecule was needed to understand the effect of HFIP and TFE on the reactions. Access to reliable experimental data ensured the chosen methodology was sufficient for modelling each system well. Confidence in the insights from these studies is thus gained and enables feedback to be provided about the choice of substrate and solvent.