Integrative Theory/Experiment‐Driven Exploration of a Multicomponent Reaction towards Imidazoline‐2‐(thi)ones

Predicting reactivity in multicomponent reactions (MCRs) is extremely difficult. These reactions proceed by multiple pathways and are inherently associated with a potentially large variation of reactants and functional groups. To date, theoretical chemistry has been used in hindsight to verify experimental observations. However, its use in the early stages of the development of a (multicomponent) reaction process can prevent laborious and time-consuming optimization studies by pinpointing the most relevant parameter(s) in the reactivity, thus focusing experimental efforts. Herein, we discuss a study that truly integrates theoretical and synthetic chemistry to unravel in full detail the complex and intricate reaction characteristics of the novel versatile MCR of -acidic iso(thio)cyanates, amines and aldehydes to access densely functionalized imidazoline-2-(thi)ones.