Squaramide-Functionalized Coordination Capsule as Hydrogen-Bond-Donor Catalyst for Efficient Friedel-Crafts Alkylation

Abstract

A squaramide-functionalized tetranuclear coordination capsule was constructed as an efficient catalyst for Friedel-Crafts alkylation. The supramolecular architecture suppresses self-association and creates a confined cavity enriched with directional hydrogenbonding sites. This defined microenvironment enables substrate encapsulation, promotes activation, and stabilizes a preorganized conformation, thereby accelerating the nucleophilic addition step.Hydrogen-bond-donating (HBD) organocatalysts, including urea, squaramide, and thiourea derivatives, have emerged as promising biomimetic alternatives to enzymes. 1,2 Squaramides, in particular, offer enhanced acidity, stability, and directional hydrogen-bonding interactions. 3,4 Although homogeneous HBD catalysts can achieve high yields and selectivity, intermolecular self-association can hinder substrate recognition and reduce catalytic efficiency. 5,6 Coordination capsules, discrete supramolecular assemblies formed through the coordinationdriven self-assembly of transition-metal ions with functional organic ligands. 7,8 These structures possess well-defined geometries, rigid frameworks, and internal cavities with precise dimensions that mimic enzyme active sites. 9,10 Host-guest interactions, such as hydrogen bonding, π-π interactions, and electrostatic forces, facilitate specific binding analogous to the classical lock-key model. 11,12 By incorporating HBD sites within these confined cavities, catalytic centers can be spatially isolated, preventing self-association and enabling selective substrate recognition and stabilization of reactive intermediates. 13 To this end, we designed and constructed a squaramide-functionalized tetranuclear coordination capsule, in which the rigid framework creates a confined cavity enriched with directional hydrogen-bonding sites.The Friedel-Crafts alkylation of indole with β-nitroalkenes, serves as an ideal model reaction for evaluating the catalytic performance of the HBD-functionalized capsule. This reaction is widely used to construct tryptamine derivatives, which are key intermediates for biologically relevant molecules including