Efficient and accurate description of Diels-Alder reactions using density functional theory

Modeling chemical reactions using Quantum Chemistry is a widely used predictive strategy capable to complement experiments in order to understand the intrinsic mech- anisms guiding the chemicals towards the most favorable reaction products. However, to do so, it is mandatory to use reliable and computationally tractable theoretical meth- ods. In this work, we focus on six Diels-Alder reactions of increasing complexity and perform an extensive benchmark of middle- to low-cost computational approaches to predict the characteristic reactions energy barriers. We found that Density Functional Theory, using the ωB97XD, LC-ωPBE, CAM-B3LYP, M11 and MN12SX functionals, with empirical dispersion corrections coupled to an affordable 6-31G basis set, provides quality results for this class of reactions, at a small computational effort. Such efficient and reliable simulation protocol opens perspectives for hybrid QM/MM molecular dynamics simulations of Diels-Alder reactions including explicit solvation.