Synthesis of Both Enantiomers of Nine‐Membered CF<sub>3</sub>‐Substituted Heterocycles Using a Single Chiral Ligand: Palladium‐Catalyzed Decarboxylative Ring Expansion with Kinetic Resolution
Hiroto Uno, Nagender Punna, Etsuko Tokunaga, Motoo Shiro, Norio Shibata
Abstract
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.