[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 M.C. Obled,
Albert Poater,
Luigi Cavallo,
Catherine S.J. Cazin,
Steven P. Nolan,
Michal Szostak
Affiliations
Tongliang Zhou
Department of Chemistry, Rutgers University, 73 Warren Street, Newark, NJ 07102, USA
Siyue Ma
Department of Chemistry, Rutgers University, 73 Warren Street, Newark, NJ 07102, USA
Fady Nahra
Department of Chemistry and Center for Sustainable Chemistry, Ghent University, Krijgslaan 281, S-3, 9000 Ghent, Belgium; Separation and Conversion Technology Unit, VITO (Flemish Institute for Technological Research), Boeretang 200, 2400 Mol, Belgium
Alan M.C. Obled
EaStCHEM School of Chemistry, University of St Andrews, St Andrews, KY16 9ST, UK
Albert Poater
Institut de Química Computacional i Catàlisi and Departament de Química, Universitat de Girona, c/ Maria Aurèlia Capmany 69, Campus Montilivi, 17003 Girona, Catalonia, Spain; Corresponding author
Luigi Cavallo
King Abdullah University of Science & Technology, KAUST Catalysis Center (KCC), 23955-6900 Thuwal, Saudi Arabia
Catherine S.J. Cazin
Department of Chemistry and Center for Sustainable Chemistry, Ghent University, Krijgslaan 281, S-3, 9000 Ghent, Belgium
Steven P. Nolan
Department of Chemistry and Center for Sustainable Chemistry, Ghent University, Krijgslaan 281, S-3, 9000 Ghent, Belgium; Corresponding author
Michal Szostak
Department of Chemistry, Rutgers University, 73 Warren Street, Newark, NJ 07102, USA; Corresponding author
Summary: 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.
