For the case of Paal-Knorr-furan synthesis, the USPTO 'Ring Breaker' is not able to predict a disconnection for substrates 1 and 2 in Figure . Whereas, the 'Ring Breaker' model trained on the Reaxys data predicts the literature disconnection for both substrate 1 (template rank 1, p=0.983) and substrate 2 (template rank 1, p=0.998) in Figure with a high probability. The case of pyrrole synthesis further highlights an interesting problem, whereby the correct disconnection can be predicted by the USPTO 'Ring Breaker' model for a simplified ring system (Figure , substrate 3). However, when the molecular complexity around the ring system was increased by replacement of the methyl groups with phenyl groups (Figure , substrate 4), the model failed to respond to the change and was not able to predict an outcome. On the other hand, the 'Ring Breaker' model trained on Reaxys was able to correctly identify the ring system (Figure , substrate 3) and predict the retrosynthetic disconnection reported in the literature. This highlights the underlying problem of template based approaches. The templates must be specific enough to yield a substructure match to the compound they are applied to and produce feasible reactants, whilst being general enough to be applicable across a broad range of suitable compounds without being promiscuous. Balancing these two requirements means that in cases such as the pyrrole synthesis, the template predicted for the simplified ring system cannot be applied to the more complex ring system shown and is further exemplified in the supporting information (SI_3). In contrast to 'Ring Breaker', the standard model is only able to predict the correct set of precursors for compound 2, which uses the Paal-Knorr-furan synthesis. obtained from the literature employing commonly used ring formations. For each prediction, the patent id or Reaxys id corresponding to the template used has been given as a precedent. In all cases, the probability 'p(x)' of predicting the template for the given compound has been shown, where 'x' refers to the prediction's rank (i.e. 'p(1) = 0.983' means the first prediction with an associated probability of 0.983). In cases where the precursors have been highlighted in a box, the predicted disconnection matches that reported in the literature or is the correct one as identified by expert chemists, the notation is equivalent for consistency. The literature reference from which the compound was obtained is given for each example where appropriate. In cases where the literature reference has not been given, the compound was purposefully simplified to determine if the correct disconnection could be predicted. We have refrained from exhaustively showing all possible disconnections and have chosen the first prediction that can be applied to generate a set of reactants, regardless of whether they reflect the 'ground truth', to show the raw predictions. Models trained on the USPTO and Reaxys datasets are complementary in this case, whereby predictions that can be made with one may not necessarily be made with the other.