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 mechanisms guiding the chemicals towards the most favorable reaction products. However, at this purpose, it is mandatory to use reliable and computationally tractable theoretical methods. 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.