A "Pool and Split" Approach to the Optimization of Challenging Pd-Catalyzed C-N Cross-Coupling Reactions.

A screening method for the rapid identification of catalytic conditions for Pd-catalyzed C-N cross-coupling reactions is reported. The strategy evaluates mixtures of precatalysts, ligands, and bases to identify productive conditions that are subsequently optimized through two deconvolution steps, which uncover the active catalyst and identify the optimal solvent and base for the catalytic system. The efficacy of this approach was demonstrated through application to a previously reported reaction, whereby both the literature conditions and additional solutions were retrieved.