Accelerated Reactivity Mechanism and Interpretable Machine Learning Model of N-Sulfonylimines Towards Fast Multicomponent Reactions

Abstract

Predicting the outcome of chemical reactions using machine learning models has emerged as a promising research area in chemical science. However, the use of such models to prospectively test new reactions by interpreting chemical reactivity is limited. We have developed a new fast and one-pot multicomponent reaction of <i>N</i>-sulfonylimines with heterogenous reactivity. Fast reaction times (<5 min) for both acyclic and cyclic sulfonylimine encouraged us to investigate plausible reaction mechanisms using quantum mechanics to identify intermediates and transition states. The heterogeneous reactivity of <i>N</i>-sulfonylimine lead us to develop a human-interpretable machine learning model using positive and negative reaction profiles. We introduce chemical reactivity flowcharts to help chemists interpret the decisions made by the machine learning model for understanding heterogeneous reactivity of <i>N-</i>sulfonylimines. The model learns chemical patterns to accurately predict the reactivity of <i>N</i>-sulfonylimine with different carboxylic acids and can be used to suggest new reactions to elucidate the substrate scope of the reaction. We believe our human-interpretable machine learning approach is a general strategy that is useful to understand chemical reactivity of components for any multicomponent reaction to enhance synthesis of drug-like libraries.

Accelerated Reactivity Mechanism and Interpretable Machine Learning Model of N-Sulfonylimines toward Fast Multicomponent Reactions

“…In summary, we have developed a fast MCR of acyclic or cyclic N -sulfonylimines that was used as a representative reaction type to develop ML models for predicting reaction outcomes in a blind prospective manner . The fast and peculiar reactivity mechanism of N -sulfonylimines was explained using DFT calculation to understand the critical role of transition states and intermediates.…”