Computational chemistry has become an indispensable tool in modern organic synthesis, enabling the prediction of reactivity and selectivity and providing mechanistic insight that is often inaccessible through experiment alone. The strategic integration of computational studies with synthetic experimentation offers a powerful framework for understanding and controlling chemical transformations. This presentation highlights the effectiveness of this synergistic approach across a range of contemporary reactions.
We showcase applications in photoredox catalysis, radical functionalization and substitution processes, where computational investigations have elucidated key mechanistic and energetic features governing reactivity and selectivity. In particular, theoretical studies have identified critical parameters controlling polarized and open-shell reaction pathways, enabling rational optimization of reaction conditions. This combined strategy has facilitated the divergent synthesis of polyfunctionalized bioactive heterocycles and the late-stage modification of complex, pharmaceutically relevant molecules.
Beyond synthetic methodology, computational tools have been applied to materials design and to fundamental studies of organic reactivity, including torquoselectivity and captodative-substitution-induced acceleration effects in pericyclic transformations. Collectively, these studies reveal intriguing structure–reactivity relationships and highlight the potential of a sustainable, predictive, and computer-aided synthetic design paradigm for the development of bioactive molecules and functional materials.