From a query in Reaxys (see SI, subsection S1), we selected 10 C-H activation reactions with Pd(OAc) 2 as the catalyst and multiple directing groups and/or symmetry unequivalent reaction sites. Using our QM workflow, we were able to predict the regioselectivity of 9 out of 10 molecules (semi-)correctly. Five reaction sites were predicted to be within 1 kcal/mol of another possible reaction site in the reactant and were therefore classified as semi-correct, meaning we can not predict with our model which of the two regioisomers will be the main product of the reaction. Refinement using r 2 SCAN-3c single-point calculations did not result in better agreement with experimental observations. The 10 molecules with their experimentally observed main reaction site in green and all predicted reaction sites within a 1 kcal/mol threshold as a blue circle are shown in Figure . Using the previously mentioned approach following Tomberg et al. , we were able to obtain 4 out of 10 correct predictions. This is slightly worse than a null model that guesses the reaction site at random which would yield an accuracy of 0.46. This can be attributed to the fact that no data is available for several relevant C-H bonds in these 10 molecules. For 3 out of the 10 molecules, no pre-computed data for any of the C-H bonds was available, therefore, no prediction can be made.