Nucleophilic ring-opening reactions of azetidine-2-carboxylic acid-derived ammonium salts with fluoride (F⁻) to afford α-fluoro-γ-aminobutyric acid (α-fluoro-GABA) derivatives were successfully demonstrated. For example, the nucleophilic ring-opening reaction of 1-benzyl-2-(tert-butoxycarbonyl)-1-methylazetidin-1-ium triflate with 1.2 equivalents of tetramethylammonium fluoride (Me₄NF) in DMF at room temperature proceeded preferentially at the 2-position and afforded tert-butyl 4-(benzyl(methyl)amino)-2-fluorobutanoate. This protocol is applicable to the syntheses of enantioenriched α-fluoro-GABA derivatives. The reactions of diastereomerically pure N-((S)-1-phenylethyl)azetidin-1-ium salts provided enantioenriched (91% ee) tert-butyl (S)-2-fluoro-4-(methylamino)butanoate.

成功证明了氮杂环丁烷-2-羧酸衍生的铵盐与氟化物（F ^-）的亲核开环反应，得到α-氟-γ-氨基丁酸（α-氟-GABA）衍生物。例如，1-苄基-2-(叔丁氧基羰基)-1-甲基氮杂环丁烷-1-三氟甲磺酸鎓与1.2当量四甲基氟化铵(Me ₄ NF)在DMF中在室温下的亲核开环反应优先在2-位，得到4-(苄基(甲基)氨基)-2-氟丁酸叔丁酯。该方案适用于对映体富集的 α-氟-GABA 衍生物的合成。非对映体纯N -(( S)-1-苯乙基)氮杂环丁烷-1-鎓盐提供对映体富集的(91％ee) ( S ) -2-氟-4-(甲基氨基)丁酸叔丁酯。