Mild Friedel-Crafts Reactions inside a Hexameric Resorcinarene Capsule: C-Cl Bond Activation through Hydrogen Bonding to Bridging Water Molecules

A novel catalytic feature of a hexameric resorcinarene capsule is highlighted. The self-assembled cage was exploited to promote the Friedel-Crafts benzylation of several arenes and heteroarenes with benzyl chloride under mild conditions. Calculations showed that there are catalytically relevant hydrogen-bonding interactions between the bridging water molecules of the capsule and benzyl chloride, which is fundamental for the activation of the C-Cl bond. The capsule controls the reaction outcome. Inside the inner cavity of the capsule, N-methylpyrrole is preferentially benzylated in the unusual -position while mesitylene reacts faster than 1,3-dimethoxybenzene despite the greater -nucleophilicity of the latter compound.