Cooperative catalysis in a crystalline framework with templated acid–base sites

Nature uses weakly basic residues in conjunction with weakly acidic residues to catalyze challenging heterolytic bond transformations. Here, we show that these cooperative effects can be replicated in a metal–organic framework containing bifunctional Brønsted acid–base sites. Using a templating strategy, we show, unambiguously, that the co-localization of acid and base sites is key to catalytic activity. Specifically, a thermolabile crosslinker containing tertiary ester and tertiary carbamate linkages is used to tether carboxylic acid and benzylamine pairs in close proximity during framework synthesis. These templated materials are over four-fold more active aldol condensation catalysts than non-templated materials containing randomly distributed acid and base sites. Together, this work establishes metal–organic frameworks as an exciting platform for cooperative acid–base catalysis that couples the advantages of heterogeneous catalysts with the structural precision of enzymes.