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Double Regioselective Asymmetric C‐Allylation of Isoxazolinones: Iridium‐Catalyzed N‐Allylation Followed by an Aza‐Cope Rearrangement
Author(s) -
Rieckhoff Stefan,
Meisner Jan,
Kästner Johannes,
Frey Wolfgang,
Peters René
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201710940
Subject(s) - regioselectivity , enantioselective synthesis , chemistry , nucleophile , phosphoramidite , iridium , catalysis , combinatorial chemistry , chirality (physics) , stereochemistry , organic chemistry , dna , biochemistry , oligonucleotide , chiral symmetry breaking , physics , quantum mechanics , nambu–jona lasinio model , quark
Isoxazolinones are biologically and synthetically interesting densely functionalized heterocycles, which for a long time were not accessible in enantioenriched form by asymmetric catalysis. Next to the deficit of enantioselective methods, the functionalization of isoxazolinones is often plagued by regioselectivity issues due to the competition of various nucleophilic centers within the heterocycles. We report the first regio‐ and enantioselective C‐allylations of isoxazolinones. These occur with high regioselectivity in favor of the linear allylation products, although Ir phosphoramidite catalysts were used, which commonly results in branched isomers. Our studies suggest that this outcome is the result of a reaction cascade via an initial regio‐ and enantioselective N‐allylation to provide a branched allyl intermediate, followed by a spontaneous [3,3]‐rearrangement resulting in chirality transfer.