Figure shows the kinetic profile of the reaction (i.e., yield of 3a over time) catalyzed by Pd@MIL-101-NH2(Cr) and by Pd(OAc)2 (3 mol% of Pd in both instances). The relative intensity of tetramer 4a over time is also presented for these two catalytic systems (see also Figure for a representation including trimer 5a). Importantly, the similarity of the plots indicates that the catalytically active species produced from Pd@MIL-101-NH2(Cr) are essentially the same as those formed from Pd(OAc)2. Tetramer 4a builds up quickly at the start of the reaction, reaching a maximum concentration at t = 30 min when the yield of 3a is already close to 80%. After this time, the concentration of these oxidative-addition Pd species quickly diminishes as the concentration of bromide 1a depletes, and the yield of 3a reaches 94% (t = 55 min). From this point, the yield of 3a remains essentially constant, and the oxidative-addition intermediates reach a steady state. The fact that the yield of 3a does not progress further to >99%, and that the relative intensity of 4a remains constant, indicates a lack of boronic acid available to use in the transmetalation step. To test this hypothesis, additional boronic acid 2a (1 equiv.) and potassium fluoride (2 equiv.) were added to the reaction mixture at t = 125 min, and the reaction was monitored until t = 135 min. We observed then that oxidative-addition intermediate 4a was fully consumed, and at the same time the yield of 3a increased to >99%. Although this indicates that the oxidative-addition tetramers are consumed upon reaction with boronic acid 2a, at this point we could not distinguish whether a direct transmetalation from 4a occurs or, alternatively, a breakdown into an oxidative-addition monomer is promoted upon reaction with the boronic acid. We therefore turned to density functional theory (DFT) calculations to try to understand the reactivity of 4a and 7a. The computational study of the transmetalation step started by studying the reaction of tetramer 4a with fluorodihydroxy(phenyl)borate (8a) (Figure ). Fluoroborates are formed under the reaction conditions when fluoride salts are used as the base. In the initial step of the transmetalation, borate 8a enters from below the plane of the four palladium atoms and coordinates to one of the four Pd centers, forming a Pd-O bond, with concomitant breaking of Pd-Br bond to the central bromide. Since this central bromide in 4a was coordinated to three additional Pd centers, the bond-breaking step is very easy, and has a low activation free energy of 7.9 kcal/mol, and a reaction free energy of -1.0 kcal/mol (Int1). Next, a p-phenyl interaction replaces the second Pd-Br bond, through another very easy process with an activation free energy of only 1.9 kcal/mol, and a reaction free energy of -2.0 kcal/mol (Int2). Now the tetramer is set for the actual transmetalation step, where the Pd-C s bond is formed (Int3). The barrier is very low, only 10.0 kcal/mol relative to the reacting intermediate. The very low trans influence of the bridging bromide is probably facilitating the formation of the Pd-C bond, and the reaction is very exergonic, leading to a tetramer with one of the Pd(II) species bearing two aryl groups. In this same step, BF(OH)2 spontaneously decoordinates from Pd, and is replaced by a Pd-Br bond. Overall, all the steps involved in the transmetalation process were found to be very easy. This might be because no strong bonds in the palladium cluster need to be broken. As the Pd-Br interaction decreases at the reacting palladium center, the remaining Pd-Br interactions are strengthened at the spectator Pd sites, leading to very low activation energies. As tetramer 4a has an unfavorable enthalpy of formation (Figure ), it is very susceptible to react, but it still forms in substantial amounts due to the entropic increase in its formation. The fact that it is possible for this tetramer to form relies on the coordination features of halides, and the absence of other stronger donor ligands (vide infra). Phosphines and carbenes interact strongly with palladium, and thus minimize its aggregation. However, the formation of reactive palladium intermediates from complexes bearing these ligands requires ligand-dissociation steps that in some cases can be rate determining. Reductive elimination of two aryl groups from Pd(II) is usually a straightforward process, and also here we find low activation energies of only 11.6 kcal/mol leading to a Pd(0) species with the product coordinated (Int4).