Internal validation techniques (k-fold = 0.75 and R 2 pred = 0.83) indicated a statistically robust model. The model was predictive with an average prediction error (MAE) of 0.26 kcal/mol. We then evaluated two new out-of-sample substrates not included in the initial data set. The predicted reaction outputs of the bulky ester (S19) and aromatic amide (S20) were satisfactory, albeit with a maximum MAE of 0.43 kcal/mol (Figure ). Despite the clear univariate correlation between the experimentally observed G ‡ values and the specific partial charge (CHELPG) centered on carbon C3 of the substituted cyclohexane substrate, statistical two-parameter models based on CHELPG values were discarded due to their poor predictability capability (See SI section 9). We therefore focused our attention on the molecular description of the cyclohexane substituent.