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

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.