Unveiling the role of water in the coupling of pyrroles and isocyanates to amidopyrroles inside a hexameric resorcinarene capsule

Abstract

DFT calculations uncovered the crucial role of non-structural water molecules trapped inside the cavity of a self-assembled hexameric resorcinarene capsule in the reaction between N-methylpyrrole and phenyl isocyanate to generate an amidopyrrole through two crucial steps: C–C coupling and a 1,3C → N proton wire mechanism. Incidentally, the reaction in the bulk solvent is energetically demanding and underscores the role of encapsulation. In fact, non-structural incorporation of water molecules modulates the acidity of the hexameric resorcinarene capsule through hydrogen-bonded networks. This results in a shift in the rate-determining transition state to the initial C–C coupling step inside the capsule, as opposed to the energy intensive proton-wire mechanism in solution. Thus, the incorporated water molecules within the supramolecular cavity helps in accelerating the overall rate of the acid-catalyzed transformation. Our work, thus, indicates the advantage of the ubiquitous presence of water-enriched local domains in providing utmost control to the supramolecule in the catalytic process. These local hydrophilic domains with water clusters, encapsulated within organic molecules, emulate the kinetics, selectivity and mass transfer observed in some natural processes. The enhanced catalytic activity is primarily attributed to water molecule’s ability to stabilize the reactants, products, intermediates or transition states through remote bond polarization, or proton shuttling, or ability of water to act as a co-catalyst.