Prior to real experimentation, we wanted to understand the performance of MTBO in simulated studies. We examined two literature reports that contain experimental results from Suzuki-Miyaura coupling reactions, and one report with results from a Buchwald-Hartwig cross-coupling (demonstrated in the Supporting Information), building a predictive model for the reaction yield to behave as the ground-truth for simulated optimization studies. Buchwald-Hartwig and Suzuki-Miyaura couplings are ubiquitous in the pharmaceutical and fine chemicals industries as they allow rapid construction of aromatic scaffolds through reactions with few impurities. We therefore chose these reaction classes because of their high value and applicability to real-world scenarios. More details on benchmark training can be found in the Supporting Information.