Acylative kinetic resolution of racemic heterocyclic amines with (R)-2-phenoxypropionyl chloride. Issue 24 (31st December 2016)

• Record Type: Journal Article
• Authors: Vakarov, Sergey A.; Gruzdev, Dmitry A.; Chulakov, Evgeny N.; Sadretdinova, Liliya Sh.; Tumashov, Andrey A.; Pervova, Marina G.; Ezhikova, Marina A.; Kodess, Mikhail I.; Levit, Galina L.; Krasnov, Victor P.; Charushin, Valery N.
• Is Part Of: Tetrahedron, asymmetry. Volume 27:Issue 24(2016)
• Page Start: 1231
• Page End: 1237
• Publication Date: 2016-12-31
• Subjects: Asymmetry (Chemistry) -- Periodicals; 547.005
• DOI: 10.1016/j.tetasy.2016.10.004
• Languages: English
• ISSNs: 0957-4166

Abstract

Graphical abstract: Abstract: The acylative kinetic resolution of racemic heterocyclic amines such as 3, 4-dihydro-3-methyl-2 H -[1, 4]benzoxazines, 3, 4-dihydro-3-methyl-2 H -[1, 4]benzothiazine, 2-methyl-1, 2, 3, 4-tetrahydro-quinolines and 2-methylindoline with enantiopure ( R )-2-phenoxypropionyl chloride has been studied. It has been found that acylation of 3, 4-dihydro-3-methyl-2 H -[1, 4]benzothiazine proceeds with the best stereoselectively when compared with other racemic amines. An efficient method for the preparation of ( S )-3, 4-dihydro-3-methyl-2 H -[1, 4]benzothiazine (99.4% ee ) via a kinetic resolution protocol was developed. The possibility of recycling ( R )-2-phenoxypropionic acid has been demonstrated. Abstract : ( R )-2-Phenoxypropionic acid: C9 H10 O3 [ α ]D 20 = +21.1 ( c 1.0, CHCl3 ) Source of chirality: Ethyll -lactate Absolute configuration: (2 R ) Abstract : (3 S )-7, 8-Difluoro-3, 4-dihydro-3-methyl- N -[(2′ R )-2′-phenoxypropionyl)]-2 H -[1, 4]benzoxazine: C18 H17 F2 NO3 [ α ]D 20 = +63.5 ( c 1.0, CHCl3 ) Source of chirality: Ethyll -lactate Absolute configuration: (3 S, 2′ R ) Abstract : (3 S )-3, 4-Dihydro-3-methyl- N -[(2′ R )-2′-phenoxypropionyl)]-2 H -[1, 4]benzoxazine: C18 H19 NO3 [ α ]D 20 = +117 ( c 1.0, CHCl3 ) Source of chirality: Ethyll -lactate Absolute configuration: (3 S, 2′ R ) Abstract : (3 S )-3, 4-Dihydro-3-methyl- N -[(2′ R )-2′-phenoxypropionyl)]-2 H -[1, 4]benzothiazine: C18 H19 NO2 S [ α ]D 20 = +198 ( c 1.3, CHCl3 ) Source of chirality: Ethyll -lactate Absolute configuration: (3 S, 2′ R ) Abstract : (2 S )-2-Methyl- N -[(2′ R )-(2′-phenoxypropionyl)]-1, 2, 3, 4-tetrahydroquinoline: C19 H21 NO2 [ α ]D 20 = +192 ( c 0.4, CHCl3 ) Source of chirality: Ethyll -lactate Absolute configuration: (2 S, 2′ R ) Abstract : (2 S )-6-Fluoro-2-methyl- N -[(2′ R )-(2′-phenoxypropionyl)]-1, 2, 3, 4-tetrahydroquinoline: C19 H20 FNO2 [ α ]D 20 = +214 ( c 1.0, CHCl3 ) Source of chirality: Ethyll -lactate Absolute configuration: (2 S, 2′ R ) Abstract : (2 S )-2-Methyl- N -[(2′ R )-(2′-phenoxypropionyl)]-indoline: C18 H19 NO2 [ α ]D 20 = +43.7 ( c 0.6, CHCl3 ) Source of chirality: Ethyll -lactate Absolute configuration: (2 S, 2′ R ) Abstract : (2 R )-2-Methyl- N -[(2′ R )-(2′-phenoxypropionyl)]-indoline: C18 H19 NO2 [ α ]D 20 = +1.3 ( c 0.8, CHCl3 ) Source of chirality: Ethyll -lactate Absolute configuration: (2 R, 2′ R )