Mechanistic study of Suzuki-Miyaura cross-coupling reactions via real-time monitoring

The Suzuki-Miyaura reaction is currently the most practiced cross-coupling reaction due to its broad applicability, low toxicity of the boron, and the wide variety of commercially available boronic acid substrates. Given its widespread application across pharmaceutical, materials, and fine chemical industries, the mechanism by which the reaction occurs is of considerable interest. Temporal profiling of chemical reactions provides the gold standard for increasing mechanistic understanding. However, acquiring reproducible and accurate time-course information while minimizing analyst intervention presents significant challenges.The integration of in situ analytical methods with automated sampling techniques offers a robust solution, enabling the acquisition of high-density, reliable temporal profiles for all observable species throughout a chemical transformation. These detailed reaction profiles reveal the dynamic signatures of underlying chemical processes, thereby informing process optimization and development. This dissertation advances our mechanistic understanding of the Suzuki-Miyaura cross- couplings through real-time monitoring studies under two distinct conditions: widely employed biphasic conditions and novel homogeneous aprotic conditions utilizing potassium trimethylsilanolate (TMSOK) as base. By leveraging an automated reaction monitoring platform, we have enhanced the mechanistic understanding of each catalytic system, ultimately leading to more efficient transformations.