With ArBr + 1˚ amines (3 unique reacting pairs), the literature precedent suggests a high dependence on bulky biaryl phosphine ligands , which can inhibit the unproductive β-hydride elimination pathway and prioritize the reductive elimination, will be observed. BrettPhos ligands were expected to be dominant in the reactome's variable importances , and indeed, we see that BrettPhos Pd G1 is by far the most important variable for this subdataset. Surprisingly, the even bulkier t-BuBrettPhos was not in contention for the top important variable . The ArBr + 2˚ amines (3 unique reacting pairs) show a negative dependence on the presence of P4-t-Bu, a phosphazene base, which despite known utility in cross-couplings , is universally bad for this subdataset. The other phosphazene base, P2-Et, is also ranked poorly by HiTEA (Fig. ). A recent systematic investigation of optimal standard Buchwald-Hartwig conditions noted that P2-Et underperformed other bases . With ArBr and ArI + 1˚ alcohols (both with 2 unique reacting pairs), and ArBr + amides (2 unique reacting pairs), ligands with rigid backbones and steric bulk which promote easier reductive elimination and prevent the deleterious K 2 -amidate complexes were expected to dominate, although a lower diversity of catalysts present in the variable importance analysis could be due to the lower random forest out of bag accuracy for these two reaction classes (Fig. ). For these three subdatasets, the subreactomes are in agreement with the literature's reactome with OMs RockPhos Pd G3 and OMs BrettPhos Pd G3 highlighted in HiTEA's analysis. Finally, we turn to ArCl + 1˚ amine couplings (6 unique reacting pairs). Here, the literature reports electron rich ligands that allow for more facile oxidative addition of the Ar-Cl bond and bulky scaffolds that limit the known β-hydrogen elimination pathway are preferred . However, the HTE subreactome had only Pd(OAc)2/BippyPhos as a variable of minor significance (Fig. ).