Mechanistic Study of Pd/NHC‐Catalyzed Sonogashira Reaction: Discovery of NHC‐Ethynyl Coupling Process

The product of a revealed transformation—NHC‐ethynyl coupling—was observed as a catalyst transformation pathway in the Sonogashira cross‐coupling, catalyzed by Pd/NHC complexes. The 2‐ethynylated azolium salt was isolated in individual form and fully characterized, including X‐ray analysis. A number of possible intermediates of this transformation with common formulae (NHC)nPd(C2Ph) (n=1,2) were observed and subjected to collision‐induced dissociation (CID) and infrared multiphoton dissociation (IRMPD) experiments to elucidate their structure. Measured bond dissociation energies (BDEs) and IRMPD spectra were in an excellent agreement with quantum calculations for coupling product π‐complexes with Pd0. Molecular dynamics simulations confirmed the observed multiple CID fragmentation pathways. An unconventional methodology to study catalyst evolution suggests the reported transformation to be considered in the development of new catalytic systems for alkyne functionalization reactions. Couple up: Mass spectrometry insight into the M/NHC‐catalyzed Sonogashira cross‐coupling reaction resulted in the discovery of NHC‐ethynyl coupling process. Intermediates of this transformations and 2‐ethynylated azolium cations were studied with NMR, ESI‐MS, CID, IRMPD, DFT and MD techniques.