A similar catalyzed mechanism with water acting in place of the hydroxyl reduces ∆G † to 43.5 kcal/mol. Both mechanisms have been previously discussed but were rediscovered here without explicit guidance to the exploration algorithm. YARP also identified an unreported mechanism catalyzed by a proton shuttle network formed by a water molecule and a hydroxyl group at the 6-position (Fig. ), which reduced the ∆G † to 36.1 kcal/mol. This new pathway strongly favors HEH formation and has hitherto been missed by studies relying on manual TS characterization.