Axially chiral 4-arylisoquinolones are endowed with pronounced bioactivity,a nd methods for their efficient synthesis have gained widespread attention. However,e nantioselective synthesis of axially chiral 4-arylisoquinolones by means of C À Ha ctivation has not been reported to date.D escribed here is ar hodium (III)-catalyzed C À Hb ond activation and annulation for the atroposelective synthesis of axially chiral 4arylisoquinolones.T he method employs chiral cyclopentadienyl ligands embodying ap iperidine ring as backbone and yields the atropisomers with good to excellent yields and enantioselectivity.B iological relevance of the 4-arylisoquinolones was demonstrated by their investigation in different cellular assays,l eading to the discovery of novel non-SMO (SMO = smoothened) binding Hedgehog pathwayi nhibitors.
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.
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