This study provides insights into the mechanism of the Suzuki-Miyaura cross-coupling reaction catalyzed by Pd nanoparticles immobilized into MIL-101-NH2(Cr). The excellent activity of this heterogeneous catalyst in the coupling of aryl bromides with boronic acids can be explained by the formation of tetrameric oxidative-addition palladium(II) intermediates. These species were observed by electrospray ionization high-resolution mass spectroscopy in the negative mode in the coupling of electron-poor aryl bromides with boronic acids. The weak bonding in the tetrameric oxidativeaddition species allows an easy transmetalation at room temperature (activation energy 10.0 kcal/mol); in contrast, the activation energy for the corresponding reaction with an oxidative-addition monomer was significantly higher (25.8 kcal/mol. Aryl iodides also give rise to tetrameric palladium adducts. However, the formation of stable off-cycle palladium iodide salts, such as [Pd2I4]n -, results in much lower catalytic efficiencies than those obtained with aryl bromides. The same tetrameric species have been observed in this work when using Pd(OAc)2, which leads us to conclude that Pd@MIL-101-NH2(Cr) behaves as a reservoir of very active ligandless catalytically active species. The advantage of using Pd@MIL-101-NH2(Cr) vs. Pd(OAc)2 is that in the former case, the catalyst can be filtered off and reused. When using Pd(OAc)2, the catalyst cannot be recycled, resulting in a significantly higher consumption of palladium. Thus, the synthetic efforts needed to prepare Pd@MOF catalysts can be fully justified. In "cocktail"-type systems, multiple mechanistic pathways are possible, and the electronic properties of the substrates may determine which pathway is favored in any particular case. This work suggests that tetrameric oxidative-addition palladium(II) species can provide a reaction pathway that proceeds via a very facile transmetallation step, usually the rate-limiting step in Suzuki-Miyaura cross-couplings.