We began our study by investigating the coupling reactions of 1-bromo-4-(trifluoromethyl)benzene (1a) or 1-iodo-4-(trifluoromethyl)benzene (1a') with phenylboronic acid (2a). We compared the catalytic performance of Pd@MIL-101-NH2(Cr) (2.4 nm average NP size, 7.25 wt% Pd content in the MOF, 3 mol% Pd loading in the catalytic reaction, Figure and Figure ) with that of the filtrates obtained from these same reactions. The reaction profiles (Figure ) show that starting from 1a, a yield of 94% of 3a was obtained after only 60 min with the MOF catalyst, which agrees with our previous results. Interestingly, the yield was much lower when the iodide substrate 1a' was used (35% yield of 3a after 60 min). The catalytic activity of the filtrates from both reactions was analyzed after 60 min (Figure ). After filtration, the filtrate was added to a new load of reactants without additional Pd@MIL-101-NH2(Cr) (i.e., 1a or 1a', 2a, and KF) and the mixture was left to react for a further 60 min. For aryl bromide 1a (filtrate A), an accumulated yield of 90% was obtained, which is similar to the yield obtained by using only Pd@MIL-101-NH2(Cr) (i.e., 94%, Figure ). Filtrate A, obtained from a parallel experiment, was analyzed by inductively coupled plasma optical emission spectroscopy (ICP-OES). This revealed the concentration of palladium to be very low, only 0.1 ppm. Therefore, with this low catalyst loading, a TON of ca 5 ´10 4 can be estimated. The presence of Pd in filtrate A was also confirmed by scanning transmission electron microscopy (STEM), which showed the presence of crystalline Pd NPs of 4.8 nm average size together with Pd clusters (<1 nm); MOF crystals where not observed (Figure and Figure ). In contrast, the accumulated yield of 3a when using aryl iodide 1a' (18%) indicated that filtrate B was inactive, as the second load of reactants were barely consumed. This result is in contrast with the usual reactivity of aryl iodides vs aryl bromides in crosscoupling reactions; the lower bond-dissociation energy (BDE) of C-I vs. C-Br bonds is a major factor controlling their oxidative addition to Pd(0) (BDE C-I = 67.2, C-Br = 82.6 kcal/mol). To further assess the nature of the species in filtrate A, we turned into electrospray ionization mass spectrometry (ESI-MS). Filtrate A obtained after 30 min of t1 was analyzed by ESI-MS in positive-ion mode, and palladium species were not found (Figure ). However, a series of substrate-bound palladium adducts were observed in negative-ion mode, specifically in the m/z region between 400 and 1450 (Figure ). Adducts 4a-7a were identified as oxidative-addition clusters (Pd = 1-4), with anionic tetramer 4a as the base peak of the spectrum (Figure ). The structure of oxidative-addition tetramer 4a was calculated using density functional theory (DFT) at the B3LYP-D3 level (Figure ). Related tetramers, lacking the central bromide, have been computationally proposed, but not observed experimentally.