Synthesis of (R)- and (S)-α-trifluoromethyl propanoic acids via asymmetric hydrogenation followed by salt resolution. Issue 17 (1st October 2016)

• Record Type: Journal Article
• Authors: Chen, Ming Z.; Sach, Neal W.; Nuhant, Philippe; Fadeyi, Olugbeminiyi O.; Trujillo, John; Lombardo, Vincent; Bernier, Louise; Unwalla, Ray; Flick, Andrew C.
• Is Part Of: Tetrahedron, asymmetry. Volume 27:Issue 17/18(2016)
• Page Start: 882
• Page End: 887
• Publication Date: 2016-10-01
• Subjects: Asymmetry (Chemistry) -- Periodicals; 547.005
• DOI: 10.1016/j.tetasy.2016.07.004
• Languages: English
• ISSNs: 0957-4166

Abstract

Graphical abstract: Abstract: A highly enantioselective synthesis of ( R )- and ( S )-α-trifluoromethyl (CF3 ) propanoic acids has been achieved via asymmetric hydrogenation of 2-trifluoromethylacrylic acid using RuBINAP-Cl2 catalyst followed by salt resolution with threoninol. Both enantiomers can be obtained as threoninol salts in good yield and with high enantiomeric excess. Amide coupling conditions that minimize racemization of the chiral acid have also been developed. Abstract : (2 R, 3 R )-1, 3-Dihydroxybutan-2-aminium ( R )-3, 3, 3-trifluoro-2-methylpropanoate: C8 H16 F3 NO4 [ α ]D 25 = −6.6 ( c 1.3, MeOH) Absolute configuration: (2 R, 3 R, R ) Source of chirality: Asymmetric hydrogenation and resolution ee = 94% Abstract : (2 S, 3 S )-1, 3-Dihydroxybutan-2-aminium ( S )-3, 3, 3-trifluoro-2-methylpropanoate (( S )-3): C8 H16 F3 NO4 [ α ]D 25 = +7.7 ( c 0.55, MeOH) Absolute configuration: (2 S, 3 S, S ) Source of chirality: Asymmetric hydrogenation and resolution ee = 92% Abstract : ( R )-3, 3, 3-Trifluoro-2-methyl-1-(4-phenylpiperi-din-1-yl)propan-1-one: C15 H18 F3 NO [ α ]D 25 = −2.0 ( c 0.3, MeOH) Absolute configuration: ( R ) Source of chirality: Chiral acid starting material ( R )-3 ee = 88%