Umpolung Reactivity of in Situ Derived Aryl Hydrazones: An Asymmetric Brønsted Acid Catalyzed Strategy to Access Fused Pyrazolidines

Abstract

Herein, we report an intriguing cascade strategy for synthesizing optically active fused pyrazolidines featuring three contiguous stereogenic centers. The formyl-tethered enones are templates for the developed umpolung reactivity, showcasing diverse substrate adaptability with various arylhydrazines. The chiral phosphoric acid catalyst offers stereochemical guidance, forming the fused pyrazolidines with commendable to excellent stereoselectivities. Additionally, the scalability, postsynthetic transformations, and instability of unacylated pyrazolidines have been successfully demonstrated.