Amine‐Urea‐Mediated Asymmetric Cycloadditions between Nitrile Oxides and o‐Hydroxystyrenes by Dual Activation

The first example of cinchona alkaloid-based amine-urea-mediated asymmetric 1,3-dipolar cycloadditions between nitrile oxides and o-hydroxystyrenes, based on the dual activation methodology involving both LUMO and HOMO activations, is described. In addition to stoichiometric asymmetric induction, a catalytic amount of amine-urea enables the cycloadditions in an enantioselective manner. Computational studies strongly support the HOMO activation of o-hydroxystyrenes and LUMO activation of nitrile oxides via hydrogen-bonding interactions by a Bronsted acid/base bifunctional catalyst.