Synthesis of Both Enantiomers of Nine‐Membered CF3‐Substituted Heterocycles Using a Single Chiral Ligand: Palladium‐Catalyzed Decarboxylative Ring Expansion with Kinetic Resolution. (4th March 2020)

• Record Type: Journal Article
• Authors: Uno, Hiroto; Punna, Nagender; Tokunaga, Etsuko; Shiro, Motoo; Shibata, Norio
• Is Part Of: Angewandte Chemie. Volume 132:Number 21(2020)
• Page Start: 8264
• Page End: 8271
• Publication Date: 2020-03-04
• Subjects: Asymmetrische Synthesen -- Fluor -- Heterocyclen -- Kinetische Racematspaltung -- Palladium; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201915021
• Languages: English
• ISSNs: 0044-8249

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. Abstract : Reflexionen : Die zwei enantiomeren Trifluormethylbenzoxazonine ( R )‐4 und ( S )‐4 können mit hoher Enantiomerenreinheit ausgehend von 1 mit jeweils einem Antipoden eines chiralen Liganden erhalten werden. Zunächst liefert eine doppelte decarboxylierende Ringexpansion mit kinetischer Racematspaltung von 1 mit einem chiralen Ligand/Pd‐Katalysator ( R )‐4 . Der nicht reaktive Antipode von 1 wird in einem zweiten Schritt der Pd‐Katalyse ohne chirales Auxiliar in ( S )‐4 umgewandelt.