Well-Defined N-Heterocyclic Carbenes−Palladium(II) Precatalysts for Cross-Coupling Reactions

Metal-catalyzed cross-coupling reactions, notably those permitting C-C bond formation, have witnessed a meteoritic development and are now routinely employed as a powerful synthetic tool both in academia and in industry. In this context, palladium is arguably the most studied transition metal, and tertiary phosphines occupy a preponderant place as ancillary ligands. Seriously challenging this situation, the use of N-heterocyclic carbenes (NHCs) as alternative ligands in palladium-catalyzed cross-coupling reactions is rapidly gaining in popularity. These two-electron donor ligands combine strong sigma-donating properties with a shielding steric pattern that allows for both stabilization of the metal center and enhancement of its catalytic activity. As a result, the number of well-defined NHC-containing palladium(II) complexes is growing, and their use in coupling reactions is witnessing increasing interest. In this Account, we highlight the advantages of this family of palladium complexes and review their synthesis and applications in cross-coupling chemistry. They generally exhibit high stability, allowing for indefinite storage and easy handling. The use of well-defined complexes permits a strict control of the Pd/ligand ratio (optimally 1/1), avoiding the use of excess costly ligand that usually requires end-game removal. Furthermore, it partly removes the "black box" character often associated with cross-coupling chemistry and catalyst formation. In the present Account, four main classes of NHC-containing palladium(II) complexes will be presented: palladium dimers with bridging halogens, palladacycles, palladium acetates and acetylacetonates, and finally pi-allyl complexes. These additional ligands are best described as a protecting shell that will be discarded going from the palladium(II) precatalyst to the palladium(0) true catalyst. The synthesis of all these precatalysts generally requires simple and short synthetic procedures. Their catalytic activity in different cross-coupling reactions is discussed and put into context. Remarkably, some NHC-containing catalytic systems can achieve extremely challenging coupling reactions such as the formation of tetra-ortho-biphenyl compounds and perform reactions at very low loadings of palladium (ppm levels). The chemistry described here, combining fundamental organometallic, catalysis, and pure organic methodology, remains rich in opportunities considering that only a handful of palladium(II) architectures have been studied. Hence, en route to an "ideal catalyst", [(NHC)Pd(II)] compounds exhibit remarkable stability and allow for fine-tuning of the NHC and of surrounding ligands in order to control the activation and the catalytic activity. Finally, unlike [Pd(PPh(3))(4)], [(NHC)Pd(II)] compounds have so far been examined only in palladium-mediated reactions (most often cross-coupling such as the Suzuki-Miyaura and Heck reactions), leaving a treasure trove of exciting discoveries to come.