The oxidative addition of 1-bromo-4-(trifluoromethyl)benzene (1a) to Int4, regenerating tetramer 4a, was then investigated. Replacing the p-coordinated biaryl 3a by aryl bromide 1a was found to be slightly exergonic (6.5 kcal/mol). Oxidative addition then proceeds with a very low activation free energy of 0.5 kcal/mol to regenerate tetramer 4a. The very low oxidative-addition barrier is probably due to the very bare Pd atom, where the only two ligands other than 1a are the bridging bromides. This limited stabilization of the Pd(0) leads to very high reactivity towards the reactant, but could also lead to rapid aggregation and the formation of larger Pd(0) clusters. We also calculated the transmetalation from a monomeric palladium species (7a), which resulted in an activation energy of 25.8 kcal/mol. This result indicates that it is significantly more favorable for tetramer 4a to undergo transmetalation than for monomer 7a (Figure ). Oxidative-addition tetramer 4a was also observed by ESI(-)-MS when p-fluorophenylboronic acid (2b) was used. On the other hand, the nature of the aryl bromide 1a significantly influences the formation of tetrameric intermediates 4. Only aryl bromides with electron-withdrawing groups (EWG), such as 1a (R = CF3), 1b (R = F), 1c (R = SF5), 1d (R = OCF3), 1e (R = SCF3), and 1f (R = SO2CF3) led to the formation of tetramers (4a-4f), as observed by ESI(-)-MS (Figures 7 and Figure ). With non-electron-poor aryl bromides, such as 1g (R = H), 1h (R = Me), and 1i (R = OMe), species 4 were not detected (Figure ). The stability of tetrameric oxidative-addition intermediates containing electron-donating groups (EDGs) was assessed by DFT calculations. The results showed that the formation of these species is still thermodynamically favored, however they are less stable than those containing EWGs. Replacement of the CF3 groups on the aryl group with CH3 led to a change from -22.6 kcal/mol for the formation of the tetramer (as shown in Figure ) to -15.7 kcal/mol. Note that the free-energy calculation assumes the reference state to be one [PdBr2Ar(OH2)] -and three PdBrAr(OH2)2, but the reaction mixture may actually contain more species that affect the equilibria. However, the difference between the aryl groups with EWG or EDG is probably due to the difference in stability of the respective tetramers. This difference in stability may explain why the adducts containing EDGs could not be detected by ESI(-)-MS. We carried out in situ F NMR spectroscopy studies with Pd(OAc)2 as the catalyst to avoid the use of the insoluble MOF (Figures 8 and Figure ). We used a Pd loading of 10 mol% in these experiments so that we would be able to detect palladium intermediates. Besides the expected signals for aryl halide 1a (-62.72 ppm) and product 3a (-62.36 ppm), three signals for CF3-containing species were observed: I (singlet, -61.45 ppm), II (broad singlet, -61.11 ppm), and III (transient broad singlet, -60.41 ® -60.94 ppm) (Figure ). The transient band III showed a rather constant intensity over time, reaching a steady state at ca. 93 min (Figure ) when the yield of 3a was 76%. Bands I and II showed significantly higher intensities than band III, both reaching their maximum intensities at ca. 93 min (I/II/III = 0.9/1/0.1, Figure and Figure ). The intensity of band I over time is rather similar to that of band II over time (Figure ). At t = 373 min, further boronic acid 2a (1 equiv.) and base (1 equiv.) were added to the NMR tube. This resulted in a rapid fading of bands I and II, while the chemical shift of band III moved from -60.94 to -60.41 ppm (Figure , black solid arrows). From the ESI(-)-MS analysis (Figure ), we determined that tetramer 4a was consumed when boronic acid 2a and base were added. As bands I and II also faded away when these reagents were added, this indicates that these bands may correspond to oxidative-addition intermediates. To test this idea, we compared the reaction profile of tetramer 4a as determined in Figure (black squares, cat = Pd(OAc)2) with the combined intensities of bands I and II over time, obtained from the F NMR experiments, also using Pd(OAc)2. As the conditions were different in these two experiments (i.e., reaction flask vs NMR tube, stirring rate, and catalyst loading), we have plotted the normalized intensities of 4a (ESI) and that of bands I + II (NMR) vs a normalized time-scale (t/tmax) for each experiment (Figure ). The correlation of the intensities along the reaction profile is excellent, and thus we can assign bands I and II as oxidativeaddition intermediates. The correlation is also excellent when the intensities of band I and band II are considered separately (Figure ). Note that the evolution of the yield of 3a in the NMR and ESI experiments correspond very well with each other across the normalized timescale (Figure ). The structures of the species responsible for bands I and II cannot be fully elucidated, but probably these bands correspond to tetramer 4a and a related oxidative-addition species. The latter might be a species where a bromide bond has been substituted by a water ligand, which may well occur under the conditions of the NMR experiment. This assignment is also supported by the rapid fading of the two bands after the addition of boronic acid (min 373, Figure ). When 1 equiv. of aryl bromide 1a was added (t = 418 min), bands I and II reappeared (Figure , blue arrows), which further reinforces the assignment. Elucidation of the identity of the species responsible for band III is more difficult, as this band is probably due to a number of interconverting palladium species.