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Enantioselective Formal C(sp 3 )−H Bond Activation in the Synthesis of Bioactive Spiropyrazolone Derivatives
Author(s) -
Li Houhua,
Gontla Rajesh,
Flegel Jana,
Merten Christian,
Ziegler Slava,
Antonchick Andrey P.,
Waldmann Herbert
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201811041
Subject(s) - enantioselective synthesis , annulation , formal synthesis , chemistry , pyrazolones , substrate (aquarium) , combinatorial chemistry , catalysis , stereochemistry , stereoisomerism , organic chemistry , biology , ecology
Herein, we report the first enantioselective annulation of α‐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.