Here we showcase how the workflow can be extended for the application of the workflow to a substrate with a meta-directing group. The substrate was investigated by Achar et al. and the reaction site was determined by the authors to be the H 2 with a meta:other regioselectivity of up to 25:1 and a yield up to 85%. In order to extend our approach to meta-/para-and remote-directing groups, we use a different approach to identify relevant palladacycle complexes as in points 1. and 2. outlined in section 3. Instead of using SMARTS patterns to detect pairs of ortho-directing groups and reaction sites, we detect all potential reaction sites by detecting all C-H bonds at sp 2 hybridized carbon atoms as well as all heteroatoms with lone pairs separately and remove symmetry equivalent sites. Then, we obtain all potential pairs of C-H bonds and heteroatoms as the Cartesian product of the two sets. Next, we filter out all pairs for which no reasonable 3D geometry can be generated. To determine whether or not a pair of C-H bond and heteroatom can form a reasonable 3D geometry, we generate a 3D geometry of a dummy "palladacycle"-intermediate between the substrate and a CCl 2 fragment using ETKDG. The CCl 2 fragment is used to mimic the Pd(OAc) 2 catalyst, which cannot be used since the following step relies on the Merck molecular force field (MMFF, version MMFF94s), which is not parameterized for transition metals like Pd. If the embedding fails, the corresponding pair is removed. When a 3D geometry could be obtained, we optimized the structure using the MMFF94s. Next, we calculate the sum of (out-of-plane) angle terms and torsion terms of the MMFF94s forcefield for the optimized structure. The geometry is considered reasonable if the sum of the angle and torsion terms is below a threshold of 10 kcal/mol. From here on, we proceed with the workflow as described in section 3.