[Pd(NHC)(μ-Cl)Cl]2: Versatile and Highly Reactive Complexes for Cross-Coupling Reactions that Avoid Formation of Inactive Pd(I) Off-Cycle Products
Tongliang Zhou, Siyue Ma, Fady Nahra, Alan Obled, Albert Poater, Luigi Cavallo, Catherine S. J. Cazin, Steven P. Nolan, Michal Szostak
Abstract
The development of more reactive, general, easily accessible, and readily available Pd(II)–NHC precatalysts remains a key challenge in homogeneous catalysis. In this study, we establish air-stable NHC–Pd(II) chloro-dimers, [Pd(NHC)(μ-Cl)Cl]2, as the most reactive Pd(II)–NHC catalysts developed to date. Most crucially, compared with [Pd(NHC)(allyl)Cl] complexes, replacement of the allyl throw-away ligand with chloride allows for a more facile activation step, while effectively preventing the formation of off-cycle [Pd2(μ-allyl)(μ-Cl)(NHC)2] products. The utility is demonstrated via broad compatibility with amide cross-coupling, Suzuki cross-coupling, and the direct, late-stage functionalization of pharmaceuticals. Computational studies provide key insight into the NHC–Pd(II) chloro-dimer activation pathway. A facile synthesis of NHC–Pd(II) chloro-dimers in one-pot from NHC salts is reported. Considering the tremendous utility of Pd-catalyzed cross-coupling reactions and the overwhelming success of [Pd(NHC)(allyl)Cl] precatalysts, we believe that NHC–Pd(II) chloro-dimers, [Pd(NHC)(μ-Cl)Cl]2, should be considered as go-to precatalysts of choice in cross-coupling processes.