The second reaction step involves a Chan-Lam coupling reaction between the product of the first reaction step (3b) and methylboronic acid (4b). This reaction employs a copper catalyst, which makes the reaction mechanism more complex, and validating the reaction solely based on the highest MCA and MAA is probably not sufficient. However, looking at the MCAs and MAAs we see that none of the proposed reaction centers have the highest MCA and MAA. In terms of the MAAs, the workflow did not identify any electrophilic sites in 4b, and the highest MAA is therefore found in 3b. This MAA is marked with a star ("*") as the attached proton moves to the neighboring nitrogen atom during the geometry optimization. The highest MCA is 428 kJ/mol, which is only 17 kJ/mol higher than the MCA of the proposed reaction center. Removing the proton from the proposed reaction center would make it the most nucleophilic site. However, based on predicted pKa values by MarvinSketch from ChemAxon the phenol group is more acidic, and a deprotonation of this phenol group would lower the MCA of the proposed reaction center as seen in the supporting information.