The results in Figure show that by locating the highest MCA and MAA among the two reactants (the values marked in bold), it is possible to predict the selectivity of the reaction. The most electrophilic site is the carbonyl carbon of 1a with a MAA of 395 kJ/mol, which is 89 kJ/mol higher than the second-highest MAA. The MAA of the carbonyl carbon is marked with a star ("*") as the chlorine atom acts as a leaving group during the geometry optimization when attaching the methyl anion to the carbonyl carbon. The most nucleophilic site in Figure is the primary amine of 2a with a MCA of 449 kJ/mol, which is 56 kJ/mol higher than the second-highest MCA. Hence, the experimentally observed nucleophilic acyl substitution reaction can be correctly predicted by locating the highest MCA and MAA despite the two reactants 1a and 2a having a total of 27 nucleophilic and 20 electrophilic sites identified by the workflow. Now, we will turn to Figure to analyze and validate the reaction steps proposed by Manifold and demonstrate how the workflow can be applied as a post-filtering tool. A CASP tool like Manifold usually outputs many different retrosynthetic routes, but some of the steps in the retrosynthetic routes may not be feasible due to selectivity issues. We propose using MCAs and MAAs as a tool to predict chemical selectivity and flag steps that are potentially incorrect. The retrosynthetic routes can then be ranked based on the number of warning flags similar to how retrosynthetic routes are commonly ranked based on the number of synthetic steps and the total price of building blocks. The first reaction step in Figure involves an ester amidation between 1b and 2b. However, based on the highest MCA and MAA, a more favorable reaction would be an ester amidation between two 2b compounds with MCA and MAA of 478 and 242 kJ/mol for the primary amine and the carbonyl carbon, respectively. The latter is marked with a star ("*") as the proton from the phenol group moves to the carbonyl oxygen during the geometry optimization when attaching the methyl anion to the carbonyl carbon. The MAA of the carbonyl carbon in 1b is 186 kJ/mol, which is 56 kJ/mol lower than the highest MAA. In fact, another site in 1b has a MAA that is 35 kJ/mol higher than the MAA of the carbonyl carbon. This reaction step should therefore be flagged as the chance of this reaction step being a success is low. Instead, one could imagine a similar retrosynthetic route starting with a nucleophilic acyl substitution similar to the one shown in Figure by replacing 1b with 1a.