Quantitative Determination of Active Species Transforming the R‑NHC Coupling Process under Catalytic Conditions

• Published in: Inorganic chemistry 2024-02, Vol.63 (6), p.2967-2976
• Main Authors: Patil, Ekaterina D., Burykina, Julia V., Eremin, Dmitry B., Boiko, Daniil A., Shepelenko, Konstantin E., Ilyushenkova, Valentina V., Chernyshev, Victor M., Ananikov, Valentine P.
• Format: Article
• Language: English
• ISSN: 0020-1669; 1520-510X
• DOI: 10.1021/acs.inorgchem.3c03614

Palladium complexes with N-heterocyclic carbenes (Pd/NHC) serve as prominent precatalysts in numerous Pd-catalyzed organic reactions. While the evolution of Pd/NHC complexes, which involves the cleavage of the Pd–C­(NHC) bond via reductive elimination and dissociation, is acknowledged to influence the catalysis mechanism and the performance of the catalytic systems, conventional analytic techniques [such as NMR, IR, UV–vis, gas chromatography–mass spectrometry (GC–MS), and high-performance liquid chromatography (HPLC)] frequently fail to quantitatively monitor the transformations of Pd/NHC complexes at catalyst concentrations typical of real-world conditions (below approximately 1 mol %). In this study, for the first time, we show the viability of using electrospray ionization mass spectrometry (ESI-MS). This approach was combined with the use of selectively deuterated H-NHC, Ph-NHC, and O-NHC coupling products as internal standards, allowing for an in-depth quantitative analysis of the evolution of Pd/NHC catalysts within actual catalytic systems. The reliability of this approach was affirmed by aligning the ESI-MS results with the NMR spectroscopy data obtained at greater Pd/NHC precatalyst concentrations (2–5 mol %) in the Mizoroki–Heck, Sonogashira, and alkyne transfer hydrogenation reactions. The efficacy of the ESI-MS methodology was further demonstrated through its application in the Mizoroki–Heck reaction at Pd/NHC loadings of 5, 0.5, 0.05, and 0.005 mol %. In this work, for the first time, we present a methodology for the quantitative characterization of pivotal catalyst transformation processes commonly observed in M/NHC systems.