Noncovalent Catalysis for Enantioselective Direct Aldol Reaction of 3-Acetylcoumarins to Pyrazole-4,5-diones

The first catalytic enantioselective direct aldol reaction of 3-acetylcoumarins to pyrazole-4,5-diones is reported and shown to proceed through noncovalent substrate activation by a quinine-derived bifunctional tertiary amino-amide as the catalyst. The densely functionalized products, consisting of an oxygen-containing quaternary stereocenter and bearing two biologically relevant heterocycles, are generally obtained in high yields with moderate to excellent enantioselectivities.