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

Angew Chem Int Ed Engl. 2018 May 4;57(19):5423-5428. doi: 10.1002/anie.201801642. Epub 2018 Apr 6.

Abstract

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 β-position while mesitylene reacts faster than 1,3-dimethoxybenzene despite the greater π-nucleophilicity of the latter compound.

Keywords: Friedel-Crafts reaction; hydrogen bonding; resorcinarenes; self-assembled capsules; supramolecular catalysis.