Enantioselective Synthesis of Unsymmetrical Diaryl-Substituted Spirocyclohexanonepyrazolones through a Cascade [4+2]Double Michael Addition

The spirocyclic pyrazolones are an important class of molecular structures with significant biological and pharmaceutical activities. Herein, we demonstrate that the combination of a Cinchona-based chiral primary amine and an ortho-fluorobenzoic acid is an efficient catalyst system for the double Michael addition of arylidenepyrazolones with ,-unsaturated ketones, providing chiral unsymmetrical 6,10-diaryl-substituted spiro[cyclohexanone-pyrazolone] derivatives in high yields (up to 98%) with good diastereoselectivities and excellent enantioselectivities (up to 88:12 dr, 99% ee).