Machine Learning Enables a Top-Down Approach to Mechanistic Elucidation in Asymmetric Catalysis

General reaction behavior is rarely reported in asymmetric catalysis, not simply because it is difficult to achieve, but also due to the methods used for its identification and study. Traditional approaches involve compartmentalization, where the impact of individual components is initially analyzed, followed by assimilation using simple response and structure matching techniques. However, extending this method to accommodate complex conditions and diverse reactions proves challenging. Here, we present a data-driven method that relies on clusterwise linear regression to derive and predictively apply general mechanistic models of enantioinduction, with minimal human intervention. When applied to the palladium-catalyzed decarboxylative asymmetric allylic alkylation (DAAA) reaction, unexpected interactions governing enantioselectivity are revealed, supported by high-level computations and additional experiments. Our results demonstrate this workflow as a powerful tool for automating mechanistic elucidation and effectively identifying general reaction performance.