Studies on the Synthesis of Novel Four-Membered Cyclic Oxaphosphetanes via Intramolecular Mitsunobu Reaction of Bishydroxyalkylphosphinic Acids

Abstract

Studies on the synthesis of novel four-membered cyclic oxaphosphetanes from bishydroxyphosphinic acids is reported. Investigations showed that the conversion proceeds through an intramolecular Mitsunobu cyclisation of bishydroxyphosphinic acids with a mixture of triphenylphosphine and diisopropylazodicarboxylate (DIAD) in toluene–CH₂Cl₂ at room temperature. The treatment of two diastereomers of bishydroxymethylphosphinic acids (dl pair and meso) with a mixture of triphenylphosphine and DIAD gives only one stereoisomer of the cyclic oxaphosphetane.

Key words

bishydroxyphosphinic acids - oxetanes - oxaphosphetane - cyclic phosphinic acids - Mitsunobu reaction

• References and Notes

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• 7 General Procedure for the Preparation of Cyclic Oxaphosphetanes 3 The bishydroxyalkylphosphinic acid 2 (2 mmol), obtained according to the method of our previously published article,⁵ was added to a stirred mixture of triphenylphosphine (0.805 g, 3.07 mmol) and DIAD (0.6 mL, 3.07 mmol) in a mixture of dry toluene–CH₂Cl₂ (5:1, 18 mL) at 0 °C under argon, and the solution was stirred for 30 min at 0 °C. Stirring was continued for 6 h at r.t. and then MeOH (0.2 mL) was added to the reaction mixture. After 30 min the solvent was removed in vacuo. The residue was purified by chromatography (CHCl₃–MeOH) to give cyclic oxaphosphetane 3 in 41–83% yield. All products gave satisfactory spectroscopic data in accord with the assigned structures. Analytical Data for 3-Hydroxy-2,4-diphenyl-1,3-oxaphosphetane 3-Oxide (cis-3a) White solid (83%, 0.43 g); mp ca. 320 °C (decomp.). ¹H NMR (400 MHz, DMSO-d ₆): δ = 5.64 (d, 2 H, J _HP = 1.6 Hz), 7.21 (t, 2 H, J = 7.6 Hz), 7.32 (t, 4 H, J = 8.0 Hz), 7.41 (d, 4 H, J = 7.6 Hz) ppm. ¹³C NMR (100.6 MHz, DMSO-d ₆): δ = 97.9 (d, J _PC = 72.3 Hz), 126.6, 126.9 (d, J _PC = 4.4 Hz), 128.07, 140.5 (d, J _PC = 12.5 Hz) ppm. ³¹P NMR (162 MHz, DMSO-d ₆/H₃PO₄): δ = 26.81 ppm. HRMS: m/z calcd for C₁₄H₁₃O₃P [MNa⁺]: 283.0500; found 283.0497.