Challenges with Literature-Derived Data in Machine Learning for Yield Prediction: A Case Study on Pd-Catalyzed Carbonylation Reactions

The application of machine learning (ML) to predict reaction yields has shown remarkable accuracy when based on high-throughput computational and experimental data. However, the accuracy significantly diminishes when leveraging literature-derived data, highlighting a gap in the predictive capability of the current ML models. This study, focusing on Pd-catalyzed carbonylation reactions, reveals that even with a data set of 2512 reactions, the best-performing model reaches only an <i>R</i>² of 0.51. Further investigations show that the models' effectiveness is predominantly confined to predictions within narrow subsets of data, closely related and from the same literature sources, rather than across the broader, heterogeneous data sets available in the literature. The reliance on data similarity, coupled with small sample sizes from the same sources, makes the model highly sensitive to inherent fluctuations typical of small data sets, adversely impacting stability, accuracy, and generalizability. The findings underscore the inherent limitations of current ML techniques in leveraging literature-derived data for predicting chemical reaction yields, highlighting the need for more sophisticated approaches to handle the complexity and diversity of chemical data.