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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
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201915021
Subject(s) - trifluoromethyl , kinetic resolution , chemistry , decarboxylation , enantiomer , palladium , chiral ligand , ligand (biochemistry) , catalysis , ring (chemistry) , enantioselective synthesis , stereochemistry , medicinal chemistry , organic chemistry , biochemistry , alkyl , receptor
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.