A new strategy has been developed for the direct encapsulation of polyoxometalates (POMs) into MIL-101(Cr). The addition of phosphotungstic acid (PTA) to the synthesis mixture of MIL-101 yields the direct encapsulation of chromium-containing polyoxometalates (POMs) inside the MOF structure, with a good distribution over the MIL-101 crystals. Vibrational Spectroscopy (DRIFT, Raman, UV-Vis) reveals the partial substitution of tungsten by Cr3+ resulting in the so-called lacunary structures, which are highly active in catalysis. The medium-sized cavities of MIL-101 are occupied by POM units bigger than their pentagonal windows when this one-pot approach is followed, and no leaching is observed. These new catalysts show the highest activities reported to date at 313 K for the Knoevenagel condensation of benzaldehyde with ethyl cyanoacetate when using apolar toluene as solvent as well as when using polar DMF and ethanol, with TOFs exceeding 600 h(-1). In addition, they exhibit a remarkable activity in two acid-catalyzed reactions, the esterification of n-butanol with acetic acid in liquid phase slurry operation and the dimethyl ether production from methanol in a fixed bed gas phase operation, in contrast to the poor or absent activity of the catalysts prepared via the impregnation of the polyoxometalate in MIL-101, where the strong interaction between POM and support deteriorates the catalytic performance. (c) 2009 Elsevier Inc. All rights reserved.