[Pd(NHC)(μ-Cl)Cl]2: The Highly Reactive Air- and Moisture-Stable, Well-Defined Pd(II)-N-Heterocyclic Carbene (NHC) Complexes for Cross-Coupling Reactions.

ConspectusPalladium-catalyzed cross-coupling reactions owing to their high specificity and superb chemoselectivity represent a powerful tool for the rapid construction of C-C and C-X bonds across various areas of chemical research, including pharmaceutical development, polymer and agrochemical industries, bioactive natural products, and advanced functional materials, rendering them indispensable for modern synthetic chemists. The major driving force for the advances in this critical field is the design of increasingly more reactive and more selective ligands and precatalysts that aim not only to address challenging cross-coupling processes but also to achieve optimal reactivity, selectivity, and functional group compatibility under mild, user-friendly, operationally simple, and broadly applicable conditions. In this context, Pd(II)-N-heterocyclic carbene complexes (NHC = N-heterocyclic carbene) have garnered prevalent attention among practitioners of organic synthesis due to their unique electronic and steric characteristics that are unmatched among other ligands. In particular, the superior σ-donating ability of NHC ligands in conjunction with conformational flexibility as well as the ease of steric and electronic modification and high stability to air and moisture enable highly effective fundamental elementary steps in catalytic cycles and facile formation of well-defined complexes.The key factor in the design of well-defined, air- and moisture-stable Pd(II) precatalysts involves the incorporation of supporting ligands, which are essential for ensuring the stability of Pd(II)-NHC complexes and facile activation of Pd(II)-NHC precatalysts to catalytically active monoligated Pd(0)-NHC species under the reaction conditions. Notably, [Pd(NHC)(μ-Cl)Cl]₂ chloro dimers, which can be readily synthesized via a one-pot, atom-economic process, are the most reactive Pd(II)-NHC complexes synthesized to date. These well-defined, air- and moisture-stable dimers readily dissociate to monomers and are activated to Pd(0)-NHC catalysts under both mild and strong base conditions, showcasing enhanced reactivity and selectivity among their Pd(II)-NHC counterparts. This balance between high, operationally simple stability, which is characteristic of Pd(II) complexes together with the ease of activation to the strongly nucleophilic Pd(0)-NHC catalysts, renders [Pd(NHC)(μ-Cl)Cl]₂ the most reactive Pd(II)-NHC precatalysts developed to date for a broad range of general cross-coupling processes, including C-X, C-O, C-N, and C-S activation and enabling the direct late-stage functionalization of complex compounds decorated with a wide range of sensitive functional groups.In this Account, we outline [Pd(NHC)(μ-Cl)Cl]₂ as a highly reactive Pd(II)-NHC precatalyst that should be routinely used as the first choice Pd complexes for a wide range of challenging cross-coupling reactions. The advancements in this field over the past 20 years emphasize the critical role of catalyst design to achieve optimal reactivity. Consequently, [Pd(NHC)(μ-Cl)Cl]₂ chloro dimers should be recommended as the go-to complexes in the powerful toolbox of Pd-catalyzed cross-coupling reactions. These now commercially available Pd(II)-NHC complexes see widespread use across the synthetic chemistry community and enable the accelerated application of challenging cross-couplings in the synthesis of new molecules.