Enantioselective Formal C(sp3)-H Bond Activation in the Synthesis of Bioactive Spiropyrazolone Derivatives

Herein, we report the first enantioselective annulation of alpha-arylidene pyrazolones through a formal C(sp(3))-H activation under mild conditions enabled by highly variable Rh-III-Cp-x catalysts. The method has a wide substrate scope and proceeds with good to excellent yields and enantioselectivities. Its synthetic utility was demonstrated by the late-stage functionalization of drugs and natural products as well as the preparation of enantioenriched [3]dendralenes. Preliminary biological investigations also identified the spiropyrazolones as a novel class of Hedgehog pathway inhibitors.