Stereoselective Synthesis of γ-Fluorinated α-Amino Acids Using 2-Hydroxy-3-pinanone as an Auxiliary

Abstract

Keywords: Amino acids / Fluorine / Chiral auxiliaries / 2-Hydroxy-3-pinanone / 1-Bromo-2-fluoroethane / 3-Bromo-2-fluoropropene (+)-(S)-2-Amino-4-fluorobutanoic acid (5a) (Ͼ 96% ee), its α-methylated derivative (+)-(S)-5b (85% ee), and (−)-(S)-2-amino-4-fluoro-4-pentenoic acid (10) (81% ee) were synthesized by diastereoselective alkylation in the presence of LDA at low temperatures. Alkylation of (+)-(R,R,R)-2-hydroxy-3-pinanone based imines of glycine tert-butyl ester 1a or alanine isopropyl ester 1b with 1-bromo-2-fluoroethane (2) or 3-bromo-2-fluoropropene (7), respectively, followed by step-

Asymmetric Synthesis of γ‐Fluorinated α‐Amino Acid Derivatives

“…After cooling in a freezer for 2 h the precipitated solid was collected by filtration. [22] [α] D 20 = -18.0 (c = 1.78, H 2 O)]. The spectroscopic data for the racemate agree with previously published values.…”

“…[16][17][18][19] Recently, the growing interest in fluorinated amino acids as protein residues has created a new challenge for synthetic chemists. [20][21][22] Also α-substitution could lead to fluorinated compounds with specific conformations and stronger resistance to hydrolysis. [23] Our group has synthesized several saturated and unsaturated γ-fluorinated amino acids.…”

Synthesis of γ-fluoro-α-amino acids by Claisen rearrangement

“…Our own research interest was focused on synthesis of g-fluoro-aamino acids from glycine or alanine derivatives and 1-bromo-2-fluoroalkanes [33][34][35] or 2-fluoroallyl bromide [36][37][38]. The latter reaction gave access to 2-amino-4-fluoropent-4-enecarboxylic acid, which can be seen as an isostere of asparagine [37].…”

New matrix metalloproteinase inhibitors based on γ-fluorinated α-aminocarboxylic and α-aminohydroxamic acids

“…40 In the key step, the fluorinated building blocks are asymmetrically introduced in a-position leading to enantiomerically enriched amino acid tert-butylesters after deprotection. 41 Afterwards, these are substituted at their N-terminal position using a modified literature procedure. 29 The last step in the synthesis is the hydrolysis of the esters followed by the introduction of the hydroxamic acid functionality (Scheme 1).…”