Iminium Catalysis inside a Self-Assembled Supramolecular Capsule: Scope and Mechanistic Studies

Although iminium catalysis has become an important tool in organic chemistry, its combination with supramolecular host systems has remained largely unexplored. We report the detailed investigations into the first example of iminium catalysis inside a supramolecular host. In the case of 1,4-reductions of α,β-unsaturated aldehydes, catalytic amounts of host are able to increase the enantiomeric excess of the products formed. Several control experiments were performed and provided strong evidence that the modulation of enantiomeric excess of the reaction product indeed stems from a reaction on the inside of the capsule. The origin of the increased enantioselectivity in the capsule was investigated. Furthermore, the substrate and nucleophile scope were studied. Kinetic investigations as well as the kinetic isotope effect measured confirmed that the hydride delivery to the substrate is the rate-determining step inside the capsule. The exploration of benzothiazolidines as alternative hydride sources revealed an unexpected substitution effect of the hydride source itself. The results presented confirm that the noncovalent combination of supramolecular hosts with iminium catalysis is opening up new exciting possibilities to increase enantioselectivity in challenging reactions.