With the three different kind of runs tested here we find 19 of the 20 target reactions shown in Table . The one reaction not found by meta-MD (R2191) is shown in Figure (a). Though R10077 (Figure ) was found by meta-MD with our secondary parameter set, it was predicted to have a too high barrier (≈ 60 kcal/mol) using the GFN2-xTB RMSD-PP estimate. We note that these two target reactions (Figure ) both involve oxiranimines and have similar mechanisms. Unlike the reactions causing problems in the search from single molecule reactants above, these two reactions have low reaction energies at the GFN2-xTB level of theory (-37 kcal/mol for R2191 and -29 kcal/mol for R10077).