Copper-Catalyzed Enantioselective O-H Bond Insertions

Significance

The authors describe the first highly enantioselective insertion of carbenoids into phenolic O-H bonds using a copper catalyst and a chiral spirobox ligand. A large variety of phenolic and aliphatic alcohols could be used for the reaction, although the ee values with aliphatic alcohols were lower than with phenolic substrates. Having a methyl group in the α-position to the diazo group in the diazo ester was crucial for high enantioselectivity, but the size of the ester group had minimal effect. The products can be conveniently hydrolyzed to give α-aryloxypropionic acids, key intermediates en route to a variety of medicinal agents.