The ability of the hemilabile (P,N) MeDalphos ligand to trigger oxidative addition of iodoarenes to gold has been thoroughly studied. Competition experiments and Hammett correlations substantiate a clear preference of gold for electron-enriched substrates both in stoichiometric oxidative addition reactions and in catalytic C–C cross-coupling with 1,3,5-trimethoxybenzene. This feature markedly contrasts with the higher reactivity of electron-deprived substrates typically encountered with palladium. Based on DFT calculations and detailed analysis of the key transition states (using NBO, CDA and ETS-NOCV methods in particular), the different behavior of the two metals is proposed to result from inverse electron flow between the substrate and metal. Indeed, oxidative addition of iodobenzene is associated with a charge transfer from the substrate to the metal at the transition state for gold, but opposite for palladium. The higher electrophilicity of the gold center favors electron-rich substrates while important back-donation from palladium favors electron-poor substrates. Facile oxidative addition of iodoarenes combined with the propensity of gold(III) complexes to readily react with electron-rich (hetero)arenes prompted us to apply the (MeDalphos)AuCl complex in the catalytic arylation of indoles, a challenging but very important transformation. The gold complex proved to be very efficient, general and robust. It displays complete regioselectivity for C3 arylation, it tolerates a variety of functional groups at both the iodoarene and indole partners (NO₂, CO₂Me, Br, OTf, Bpin, OMe…) and it proceeds under mild conditions (75 °C, 2 h).

Cycling between Au(I) and Au(III) is challenging, so gold-catalyzed cross-couplings are rare. The (MeDalphos)AuCl complex, which we showed was prone to undergo oxidative addition, is reported here to efficiently catalyze the C–N coupling of aryl iodides and amines. The transformation does not require an external oxidant or a directing group. It is robust and works with a wide scope of aryl iodides and N-nucleophiles under mild conditions. Mechanistic studies, including the NMR and MS characterization of a key aryl amido Au(III) complex, strongly support a 2e redox cycle in which oxidative addition precedes transmetalation and reductive elimination is the rate-determining step.

Discrete palladium (II) complexes featuring purposely designed phosphine ligands can promote depropargylation and deallylation reactions in cell lysates. The performance of these complexes is superior to that of other palladium sources, which apparently are rapidly deactivated in such hostile complex media. This good balance between reactiv-ity and stability allows the use of these discrete phosphine palladium complexes in living mammalian cells, whereby they can mediate similar transformations. The presence of a phosphine ligand in the coordination sphere of palladi-um also provides for the introduction of targeting groups, such as hydrophobic phosphonium moieties, which facili-tate the accumulation of the complexes in mitochondria.

The hemilabile Ad ₂ P( o -C ₆ H ₄ )NMe ₂ ligand promotes fast, quantitative and irreversible oxidative addition of alkynyl and vinyl iodides to gold.