Bifunctional Squaramide-Catalyzed One-Pot Sequential Michael Addition/Dearomative Bromination: Convenient Access to Optically Active Brominated Pyrazol-5(4H)-ones with Adjacent Quaternary and Tertiary Stereocenters

The organocatalytic asymmetric, one-pot, sequential Michael addition/dearomative bromination reaction of pyrazol-5-ones to nitro olefins and N-bromosuccinimide (NBS) has been developed. Under the catalysis of a chiral bifunctional squaramide, a wide variety of chiral brominated pyrazol-5-one derivatives with contiguous quaternary and tertiary stereocenters was obtained in high yields (up to >99%) with good to excellent diastereoselectivities (62:38-99:1 dr) and uniformly high levels of enantioselectivity (92 to >99% ee). This experimentally simple process facilitates access to various enantio-enriched, multiply substituted pyrazolin-5-one derivatives, potential biologically active molecules, starting from readily available starting materials.