Strategic integration of pendant –COOH and –NH sites in a Zn-MOF for hydrogen-bond donating organocatalysis in the Friedel–Crafts alkylation reaction of indoles with β-nitrostyrenes

Abstract

Hydrogen-bond donating (HBD) sites in catalysts play a pivotal role in facilitating precise substrate activation and transition state stabilization, thereby enhancing both reactivity and selectivity in a wide range of C–C bond forming transformations. The orientation of these HBD sites in the vicinity, for the synergistic activity of catalysts, is also challenging to achieve, particularly in heterogeneous catalysis. In this work, we designed and synthesized a new eminently robust 3D metal–organic framework (MOF), [Zn₄(H(D-GluBenz))₄(H₂O)₂]_n [Zn-(D-GluBenz)], where the D-glutamic acid-based H₃(D-GluBenz) ligand acts as a dicarboxylate for a perfect strategic integration of both –COOH and –NH pendant sites for the first time. This architectural precision provides a unique active environment that makes it a hydrogen-bond donating organocatalyst for the efficient Friedel–Crafts alkylation of indoles with β-nitrostyrenes under significantly milder conditions than previously reported. In addition to having a broad substrate scope, Zn-(D-GluBenz) demonstrates excellent recyclability and robust heterogeneity. The key hydrogen bonding interactions between the HBD sites of Zn-(D-GluBenz) and the nitro group of β-nitrostyrene are confirmed through fluorescence spectroscopy, underscoring its organocatalytic nature. This work highlights the untapped potential of amino acid-based MOFs as versatile platforms for sustainable HBD-driven organocatalysis.