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Synthesis of Both Enantiomers of Nine‐Membered CF 3 ‐Substituted Heterocycles Using a Single Chiral Ligand: Palladium‐Catalyzed Decarboxylative Ring Expansion with Kinetic Resolution
Author(s) -
Uno Hiroto,
Pungender,
Tokunaga Etsuko,
Shiro Motoo,
Shibata Norio
Publication year - 2020
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.201915021
Subject(s) - trifluoromethyl , kinetic resolution , decarboxylation , chemistry , catalysis , palladium , ring (chemistry) , ligand (biochemistry) , enantiomer , chiral ligand , enantioselective synthesis , medicinal chemistry , yield (engineering) , stereochemistry , ethylene , organic chemistry , physics , receptor , biochemistry , alkyl , thermodynamics
Abstract The two enantiomers of trifluoromethyl‐benzo[ c ][1,5]oxazonines, ( R )‐ 4 and ( S )‐ 4 , can be selectively accessed with high enantiopurity by the Pd‐catalyzed ring‐expansion reaction of trifluoromethyl‐benzo[ d ][1,3]oxazinones ( 1 ) with vinyl ethylene carbonates ( 3 ) using one antipode of a chiral ligand. Initially, the reaction proceeds by a double decarboxylative ring‐expansion with kinetic resolution of 1 in the presence of a Pd‐catalyst/chiral ligand to provide ( R )‐ 4 with high enantiopurity. At the same time, the nonreactive antipode of 1 , ( S )‐ 1 , which was recovered with an impeccable s factor of up to 713 and an ideal chemical yield, was transferred into the antipode of the products, ( S )‐ 4 , with high enantiopurity by a second run of the Pd‐catalyzed double decarboxylation reaction, but this time without any chiral auxiliary. Thus, both antipodes of the chiral trifluoromethyl heterocycles 4 can be obtained in excellent enantiopurity using only a single antipode of the chiral catalyst.