Copper-Catalyzed Asymmetric Annulation Reactions of Carbenes with 2-Iminyl- or 2-Acyl-Substituted Phenols: Convenient Access to Enantioenriched 2,3-Dihydrobenzofurans

We have developed a method for the highly diastereo- and enantioselective construction of 2,3-dihydrobenzofurans bearing tetrasubstituted carbon stereocenters by means of annulation reactions between carbenes and 2-iminyl- or 2-acyl-substituted phenols through catalysis by readily accessible copper(I)/bisoxazoline catalysts under mild conditions. These reactions feature a unique mechanism in which the copper catalyst serves a dual function: first it reacts with the diazo compound to generate a metal carbene, and second, upon formation of an oxonium ylide, it acts as a Lewis acid to activate the imine or ketone for diastereo- and enantioselective cyclization.