Nucleophilic substitution catalyzed by a supramolecular cavity proceeds with retention of absolute stereochemistry.

While the reactive pocket of many enzymes has been shown to modify reactions of substrates by changing their chemical properties, examples of reactions whose stereochemical course is completely reversed are exceedingly rare. We report herein a class of water-soluble host assemblies that is capable of catalyzing the substitution reaction at a secondary benzylic carbon center to give products with overall stereochemical retention, while reaction of the same substrates in bulk solution gives products with stereochemical inversion. Such ability of a biomimetic synthetic host assembly to reverse the stereochemical outcome of a nucleophilic substitution reaction is unprecedented in the field of supramolecular host-guest catalysis.