The here developed predictive QM-based model calculates which potential reaction site is most likely to react based on its corresponding reaction energy. Following the Bell-Evans-Polanyi principle, the relative energy of the intermediate should correlate linearly with the energy of the transition state. The site with the lowest reaction energy is expected to correspond to the experimentally observed reaction site. Therefore, instead of locating the structure of the transition state, the preceding palladacycle intermediate structure is generated and optimized, as shown in Figure . Using this approximation the generation and optimization of structures simplifies greatly. In an automized workflow, all unique and possible combinations of C-H bonds and ortho-directing groups (heteroatom with lone pair) in the substrate are found following this procedure: