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

Herein, we report the first enantioselective annulation of α‐arylidene pyrazolones through a formal C(sp3)−H activation under mild conditions enabled by highly variable RhIII‐Cpx 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. The rhodium(III)‐catalyzed enantioselective annulation of α‐arylidene pyrazolones through a formal C(sp3)−H activation proceeds under very mild conditions in the presence of a novel chiral Cpx ligand. This process yields a new class of Hedgehog pathway inhibitors.