Mn(OAc)₃-Mediated Synthesis of 3-Phosphonyldihydrofurans from β-Ketophosphonates and Alkenes

Abstract

A new, general method for the synthesis of 3-phosphonyldihydrofuran derivatives has been achieved through Mn(OAc)₃-mediated radical cyclization between β-ketophosphonates and alkenes. This transformation allows the direct formation of C–C/C–O bonds and the construction of a dihydrofuran ring in one reaction with operational simplicity and excellent functional-group compatibility.

Key words

manganese - phosphonyldihydrofurans - β-ketophosphonates - alkenes - radicals

• References and Notes

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• 16 Experimental Procedure for the Synthesis of 1a Styrene (2.08 g, 20 mmol) was added to a mixture of H-diethyl phosphonate (5.52 g, 40 mmol), CuBr₂ (111.5 mg, 0.5 mmol, 2.5 mol%), FeBr₃ (162 mg, 1 mmol, 5.0 mol%), and Et₃N (2.02g, 20 mmol) in DMSO (40 mL) at r.t. under O₂ (balloon). The reaction mixture was stirred at 55 °C for 48 h. After completion of the reaction, water (20 mL) was added to the reaction mixture, and the resulting mixture was extracted with CH₂Cl₂. The organic layer was washed with 0.1 mol/L HCl (1 × 20 mL), water (3 × 20 mL), brine (1 × 20 mL), and the separated aqueous phase was extracted with CH₂Cl₂ (2 × 20 mL). The combined organic layers were dried over Na₂SO₄, filtered, and concentrated in vacuo. The residue was purified by flash chromatography on silica gel using a PE–EtOAc mixture (3:1, v/v) as the eluent to afford 1a as a light yellow oil (3.07 g, 60%). ¹H NMR (400 MHz, CDCl₃): δ = 8.01 (d, J = 8.0 Hz, 2 H), 7.59 (t, J = 7.5 Hz, 1 H), 7.47 (t, J = 8.5 Hz, 2 H), 4.17–4.09 (m, 4 H), 3.65 (d, J = 22.6 Hz, 2 H), 1.27 (t, J = 6.9 Hz, 6 H). ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 191.9 (d, J = 6.6 Hz), 136.5, 133.7, 129.0, 128.6, 62.7 (d, J = 6.5 Hz), 38.4 (d, J = 130.1 Hz), 16.2 (d, J = 6.1 Hz). ³¹P{¹H} NMR (162 MHz, CDCl₃): δ = 20.0. Other β-ketophosphonates were prepared similarly. Experimental Procedure for the Synthesis of 2q A 15 mL Schlenk tube charged with α-bromostyrene (0.377 g, 268 μL, 2.0 mmol), (4-methoxyphenyl) boronic acid (2.6 mmol, 1.3 equiv), K₃PO₄ (1.27 g, 6.0 mmol, 3.0 equiv), Pd(PPh₃)₄ (0.116 g, 5 mol%), and THF (10 mL) was heated at 80 °C for 12 h. After completion, the reaction mixture was evaporated, and the product was purified by flash silica gel column chromatography using PE as the eluent to afford 2q as a white solid (307 mg, 73%). ¹H NMR (400 MHz, CDCl₃): δ = 7.32–7.26 (m, 7 H), 6.85 (d, J = 8.8 Hz, 2 H), 5.37 (d, J = 17.0 Hz, 2 H), 3.81 (s, 3 H). ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 159.6, 149.7, 142.0, 134.2, 129.6, 128.5, 128.3, 127.8, 113.7, 113.1, 55.5. Other alkenes were prepared similarly. Experimental Procedure for the Synthesis of 3-Phosphodihydrofuran Derivatives A 15 mL Schlenk tube containing Mn(OAc)₃·H₂O (0.60 mmol, 3.0 equiv) was evacuated and purged with argon three times. β-Ketophosphonates (1, 0.40 mmol, 2.0 equiv), alkenes (2, 0.20 mmol, 1.0 equiv), and AcOH (2.0 mL) were sequentially added to the system at r.t. The reaction mixture was heated with stirring at 80 °C for 6 h. Upon completion, the reaction solution was concentrated in vacuo, then added 15 mL sat. NaHCO₃ solution, and extracted with EtOAc (3 × 10 mL). The organic layer was dried over Na₂SO₄, and concentrated under vacuum. The residue was purified by silica gel column chromatography using a PE–EtOAc mixture (from 3:1 to 1:1, v/v) as the eluent to afford the corresponding products. Diethyl (2,5,5-Triphenyl-4,5-dihydrofuran-3-yl)phosphonate (3a; New Compound) Yield 75% (65 mg); light yellow liquid. ¹H NMR (400 MHz, CDCl₃): δ = 7.95–7.93 (m, 2 H), 7.46 (d, J = 8.0 Hz, 4 H), 7.42–7.39 (m, 2 H), 7.33 (t, J = 7.6 Hz, 4 H), 7.28–7.24 (m, 2 H), 3.97–3.84 (m, 4 H), 3.78 (d, J = 3.2 Hz, 2 H), 1.12 (t, J = 7.0 Hz, 6 H). ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 163.8 (d, J = 25.8 Hz), 145.0, 130.4, 129.7, 129.0, 128.4, 127.7, 127.6, 125.7, 94.6 (d, J = 213.6 Hz), 91.5 (d, J = 11.6 Hz), 61.77 (d, J = 5.2 Hz), 47.8 (d, J = 9.4Hz), 16.26 (d, J = 6.7 Hz). ³¹P{¹H} (162 MHz, CDCl₃): δ = 16.5. HRMS: m/z calcd for C₂₆H₂₈O₄P [M + H]⁺: 435.1720; found: 435.1719.