An Efficient and Highly Regioselective Fluorination of Aziridines Using BF₃·OEt₂ as Fluorine Source

Abstract

β-Fluoro amines were prepared from the reaction of aziridines and boron trifluoride in high regioselectivity and in high yield. All three fluorine atoms of BF₃·OEt₂ were incorporated into the products when it reacted with aziridines.

Key words

aziridines - fluorination - BF₃·OEt₂ - ring-opening reaction - β-fluoro amine

References

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9

General Procedure of the Reaction of Aziridine 1 with BF ₃ ·OEt ₂ in the Presence of Alcohol: To a stirred solution of aziridine 1 (0.5 mmol) and alcohol in corresponding solvent (2.0 mL) was added BF₃·OEt₂ (0.6 mmol) under argon. The resulting mixture was stirred at 25 °C till complete consumption of substrate (monitored by TLC). The reaction mixture was quenched with 5 mL of sat. NH₄Cl aq solution. The aqueous layer was separated and extracted with CH₂Cl₂ (3 × 10 mL). The combined organic layer was dried over anhyd Na₂SO₄. The solvent was removed in vacuum and the crude product was purified by flash column chromatography on silica gel to provide corresponding β-fluoro amines.⁵ The analytical data of some products are shown below:
N -(2-Fluorohexyl)-4-methylbenzenesulfonamide (2d): 51% yield; white solid; mp 62-63 °C. ¹H NMR (300 MHz, CDCl₃, 25 °C, TMS): d = 0.88 (t, J = 6.6 Hz, 3 H), 1.27-1.63 (m, 6 H), 2.44 (s, 3 H), 2.93-3.08 (m, 1 H), 3.20-3.31 (m, 1 H), 4.43 and 4.60 (double multiplet, ² J _H-F = 51.0 Hz, 1 H), 4.78 (dd, J = 4.8, 7.2 Hz, 1 H), 7.32 (d, J = 7.8 Hz, 2 H), 7.75 (d, J = 8.7 Hz, 2 H). ¹⁹F NMR (282 MHz, CDCl₃, 25 °C, CF₃COOH): d = -186.4 (m). MS (EI): m/z (%) = 273 (1.63)(M⁺), 184 (80), 155 (100), 91 (85). IR (film): 3279, 1599, 1496 cm^-1.
N -(2-Fluorooctyl)-4-methylbenzenesulfonamide (2e): 67% yield; white solid; mp 72-73 °C. ¹H NMR (300 MHz, CDCl₃, 25 °C, TMS): d = 0.88 (t, J = 6.9 Hz, 3 H), 1.25-1.60 (m, 10 H), 2.44 (s, 3 H), 2.94-3.09 (m, 1 H), 3.21-3.32 (m, 1 H), 4.43 and 4.59 (double multiplet, ² J _H-F = 48.6 Hz, 1 H), 4.75 (dd, J = 4.8, 7.5 Hz, 1 H), 7.32 (d, J = 8.1 Hz, 2 H), 7.75 (d, J = 8.4 Hz, 2 H). ¹⁹F NMR (282 MHz, CDCl₃, 25 °C, CF₃COOH): d = -173.9 (m). MS (EI): m/z (%) = 301 (1.19) [M⁺], 184 (99), 155 (100), 146 (12), 91 (95). IR (film): 3276, 1600, 1324, 1160 cm^-1. Anal. Calcd for C₁₅H₂₄FNO₂S: C, 59.77; H, 8.03; N, 4.65. Found: C, 59.73; H, 7.97; N, 4.54.
N -(2-Fluorooctadecyl)-4-methylbenzenesulfon-amide (2f): 83% yield; white solid; mp 82-83 °C. ¹H NMR (300 MHz, CDCl₃, 25 °C, TMS): d = 0.88 (t, J = 6.6 Hz, 3 H), 1.25-1.58 (m, 30 H), 2.44 (s, 3 H), 2.93-3.08 (m, 1 H), 3.13-3.31 (m, 1 H), 4.42 and 4.58 (double multiplet, ² J _H-F = 49.2 Hz, 1 H), 4.71 (dd, J = 4.8, 7.8 Hz, 1 H), 7.32 (d, J = 8.1 Hz, 2 H), 7.74 (d, J = 8.1 Hz, 2 H). ¹⁹F NMR (282 MHz, CDCl₃, 25 °C, CF₃COOH): d = -186.6 (m). MS (EI): m/z (%) = 441 (1.14) [M⁺], 286 (35), 184 (100), 155 (59), 91 (37). IR (film): 3290, 1927, 1600, 1334, 1163 cm^-1. Anal. Calcd for C₂₅H₄₄FNO₂S: C, 67.98; H, 10.04; N, 3.17. Found: C, 68.23; H, 9.85; N: 3.20.
( S )- N -(2-Fluoro-3-phenylpropyl)-4-methylbenzene-sulfonamide (2g): 68% yield; white solid; mp 131-132 °C. ¹H NMR (300 MHz, CDCl₃, 25 °C, TMS): d = 2.43 (s, 3 H), 2.84-3.27 (m, 4 H), 4.59-4.83 (m, 1 H), 4.75-4.83 (m, 1 H), 7.14 (d, J = 6.6 Hz, 2 H), 7.25-7.32 (m, 5 H), 7.71 (d, J = 8.1 Hz, 2 H). ¹⁹F NMR (282 MHz, CDCl₃, 25 °C, CF₃COOH):
d = -184.5 (m). MS (EI): m/z (%) = 308 (0.64) [M + 1]⁺, 132 (100), 155 (41), 91 (94). IR (film): 3284, 1928, 1598, 1315, 1162 cm^-1. Anal. Calcd for C₁₆H₁₈FNO₂S: C, 62.52; H, 5.90; N, 4.56. Found: C, 656; H, 6.08; N: 4.52.