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Synthesis and reactions of α-fluoro-α-amino amides

Clayson, Joanne; Bailey, Patrick D.; Boa, Andrew N.

Authors

Joanne Clayson

Patrick D. Bailey

Abstract

N-((S)-1-Phenylethyl)halofluoroethanamides have been investigated as precursors to N-protected α-fluoro-α-amino amides by nucleophilic displacement of halide with nitrogen nucleophiles such as potassium phthalimide, sodium succinimide, sodium glutarimide, trimethylamine and sodium azide. With single diastereoisomers of the iodofluoroethanamide, clean inversion of configuration occurs at room temperature, but subsequent epimerisation may occur as a result of the liberated iodide. The α-fluoro-α-amino amides made underwent a wide variety of reactions depending on conditions, but in many cases the carbon-fluorine bond was compromised. However, reacting trimethylamine and N-((S)-1-phenylethyl)iodofluoroethanamide gave the corresponding α-fluorobetaine amide, and subsequent acidic hydrolysis led to α-fluorobetaine as the first example of an 'unprotected' α-fluoroamino acid. (C) 2008 Elsevier Ltd. All rights reserved.

Journal Article Type Article
Publication Date Feb 21, 2009
Journal TETRAHEDRON
Print ISSN 0040-4020
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 65
Issue 8
Pages 1724-1736
Institution Citation Bailey, P. D., Clayson, J., & Boa, A. N. (2009). Synthesis and reactions of α-fluoro-α-amino amides. Tetrahedron, 65(8), (1724-1736). doi:10.1016/j.tet.2008.11.061. ISSN 0040-4020
DOI https://doi.org/10.1016/j.tet.2008.11.061
Keywords Amino acids and derivatives; Peptide analogues/mimetics
Publisher URL https://www.sciencedirect.com/science/article/pii/S0040402008020322?via%3Dihub