Prediction of Major Regio-, Site-, and Diastereoisomers in Diels-Alder Reactions by Using Machine-Learning: The Importance of Physically Meaningful Descriptors

Machine learning can predict the major regio-, site-, and diastereoselective outcomes of Diels-Alder reactions better than standard quantum-mechanical methods and with accuracies exceeding 90% provided that i) the diene/dienophile substrates are represented by physical-organic descriptors reflecting the electronic and steric characteristics of their substituents and ii) the positions of such substituents relative to the reaction core are encoded (vectorized) in an informative way.