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Open AccessFeature PaperArticle

Preparative Method for Asymmetric Synthesis of (S)-2-Amino-4,4,4-trifluorobutanoic Acid

1
College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, Jiangsu, China
2
Hamari Chemicals Ltd., 1-4-29 Kunijima, Higashi-Yodogawa-ku, Osaka 533-0024, Japan
3
Department of Biochemical Engineering, Graduate School of Science and Engineering, Yamagata University, Yonezawa, Yamagata 992‑8510, Japan
4
Department of Organic Chemistry I, Faculty of Chemistry, University of the Basque Country UPV/EHU, Paseo Manuel Lardizábal 3, 20018 San Sebastián, Spain
5
IKERBASQUE, Basque Foundation for Science, María Díaz de Haro 3, Plaza Bizkaia, 48013 Bilbao, Spain
*
Authors to whom correspondence should be addressed.
Academic Editors: Rafael Chinchilla and Roman Dembinski
Molecules 2019, 24(24), 4521; https://doi.org/10.3390/molecules24244521
Received: 29 October 2019 / Revised: 6 December 2019 / Accepted: 9 December 2019 / Published: 10 December 2019
(This article belongs to the Special Issue Development of Asymmetric Synthesis)
Enantiomerically pure derivatives of 2-amino-4,4,4-trifluorobutanoic acid are in great demand as bioisostere of leucine moiety in the drug design. Here, we disclose a method specifically developed for large-scale (>150 g) preparation of the target (S)-N-Fmoc-2-amino-4,4,4-trifluorobutanoic acid. The method employs a recyclable chiral auxiliary to form the corresponding Ni(II) complex with glycine Schiff base, which is alkylated with CF3–CH2–I under basic conditions. The resultant alkylated Ni(II) complex is disassembled to reclaim the chiral auxiliary and 2-amino-4,4,4-trifluorobutanoic acid, which is in situ converted to the N-Fmoc derivative. The whole procedure was reproduced several times for consecutive preparation of over 300 g of the target (S)-N-Fmoc-2-amino-4,4,4-trifluorobutanoic acid. View Full-Text
Keywords: Ni complex; fluorinated amino acid; large-scale synthesis; asymmetric synthesis; glycine Schiff base Ni complex; fluorinated amino acid; large-scale synthesis; asymmetric synthesis; glycine Schiff base
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MDPI and ACS Style

Han, J.; Takeda, R.; Liu, X.; Konno, H.; Abe, H.; Hiramatsu, T.; Moriwaki, H.; Soloshonok, V.A. Preparative Method for Asymmetric Synthesis of (S)-2-Amino-4,4,4-trifluorobutanoic Acid. Molecules 2019, 24, 4521.

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