Extracting Mechanistic Information from an Open Data Set for a Pharma-Relevant Suzuki-Miyaura Cross-Coupling Reaction

Open reaction data sets, particularly those gathered through high-throughput experimental (HTE) reaction screening campaigns, hold considerable value in downstream data analysis and reaction understanding. Data can be used to reveal important trends. Such open reaction data are increasingly being reported and deposited to appropriate databases, particularly for the most popular chemical reactions, e.g., Suzuki-Miyaura cross-coupling (SMCC) of organohalides and organoboron compounds, catalyzed by Pd and mediated by a suitable base. While there is considerable complexity associated with SMCC reactions, as informed by many independent mechanistic studies over the years, one can bring out essential trends through detailed data analysis. In this study, we have taken an open reaction data set reported by Pfizer and evaluated the properties of closely related substrates and the effect of the reaction solvent, base, and ligands. Through a detailed analysis of the reaction outcomes, we have focused on the occurrence of a common side-product in SMCCs, resulting from protodeborylation of the organoboron coupling component. There is considerable benefit in exploring the main cross-coupled product yield compared with the amount of protoborylated compound formed. In our analysis, we have delineated several key and interesting trends, which reveal value in evaluating side-product(s)/main product yields. A Shiny app has been developed for the rapid evaluation of the SMCC reaction data set.