Quantum chemical calculations for reaction prediction in the development of synthetic methodologies

Quantum chemical calculations have been used in the development of synthetic methodologies to analyze the reaction mechanisms of the developed reactions. Their ability to estimate chemical reaction pathways, including transition state energies and connected equilibria, has led researchers to embrace their use in predicting unknown reactions. This perspective highlights strategies that leverage quantum chemical calculations for the prediction of reactions in the discovery of new methodologies. Selected examples demonstrate how computation has driven the development of unknown reactions, catalyst design, and the exploration of synthetic routes to complex molecules prior to often laborious, costly, and time-consuming experimental investigations. This perspective showcases how quantum chemical calculations drive predictive strategies to explore unknown reactions, catalysts, and synthetic routes toward complex molecules in synthetic methodology development.