Organosulfur- or Organoselenium-Induced Intramolecular Cycloaddition of β-Allenic α-Difluoromethylenephosphonic Acid Monoesters: Synthesis of Novel Cyclic Phosphate Mimics

Abstract

Novel cyclic phosphate mimics, γ-organosulfur or organoselenium substituted α-difluoromethylenephostones were synthesized in good yields with high regioselectivity under mild conditions by the electrophilic cyclization of β-allenic α-difluoro­methylenephosphonic acid monoesters induced by ArSCl or ArSeCl. The reaction represents the first example of an intramolecular addition of phosphonic acid monoesters to β-allenic carbon-carbon double bonds.

Key words

β-allenic α-difluoromethylenephosphonic acid monoester - phosphate mimic - α-difluoromethylenephostone - organoselenium - organosulfur - cyclization

References and Notes

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14

Cyclic Products 2 or 3; Typical Procedure: To a solution of 1 (0.5 mmol) in MeCN (6 mL) in a dry Schlenk tube was slowly added p-MeC₆H₄SCl or PhSeCl (0.75 mmol) in MeCN (2 mL) at -30 °C under a N₂ atmosphere. After the reaction was complete (monitored by TLC, ca. 30 min), the reaction mixture was concentrated and the residue was purified by flash chromatography on silica gel to give product 2 or 3.
Compound 2a Mp 54-55 °C. IR (KBr): 1616, 1285, 1116, 1037, 1005 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.40-7.38 (m, 2 H), 7.28-7.25 (m, 2 H), 5.05-4.92 (m, 1 H), 4.35-4.29 (m, 2 H), 2.40 (s, 3 H), 1.85 (s, 3 H), 1.74 (s, 3 H), 1.38 (t, J = 6.6 Hz, 3 H). ¹⁹F NMR (282 MHz, CDCl₃): δ = -101.08 (AB, dd, J _F-F = 308.7 Hz, J _P-F = 95.6 Hz, J _H-F = 11.6, 10.1, 7.9 Hz). ³¹P NMR (121 MHz, CDCl₃): δ = -0.58 to -2.54 (m). EIMS: m/z (%) = 348 (M⁺, 29.56), 225 (35.63), 189 (100.00), 117 (56.26), 107 (27.57), 97 (56.06), 77 (58.91). Anal. Calcd for C₁₅H₁₉F₂O₃PS: C, 51.72; H, 5.50. Found: C, 51.92; H, 5.49.
Compound 3a Mp 56-57 °C. IR (KBr): 1621, 1285, 1027, 1001 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.64-7.61 (m, 2 H), 7.49-7.28 (m, 3 H), 5.41-5.29 (m, 1 H), 4.37-4.32 (m, 2 H), 1.85 (s, 3 H), 1.75 (s, 3 H), 1.40 (t, J = 7.2 Hz, 3 H). ¹⁹F NMR (282 MHz, CDCl₃): δ = -102.16 (AB, dd, J _F-F = 311.8 Hz, J _P-F = 95.6 Hz, J _H-F = 10.2, 8.5, 7.9 Hz). ³¹P NMR (121 MHz, CDCl₃): δ = -0.71 to -2.64 (m). EIMS: m/z (%) = 382 (M⁺, 2.47), 381 (14.23), 223 (17.00), 133 (10.31), 117 (100.00), 97 (35.47), 77 (50.49), 65 (10.49), 51 (18.10). Anal. Calcd for C₁₄H₁₇F₂O₃PSe: C, 44.11; H, 4.49. Found: C, 44.12; H, 4.60.