An Effective Borate-Mediated Approach to 1-Trifluoromethyl-1-hydroxy-3-ketophosphonates, Phosphinates, and Phosphine Oxides

Abstract

Ethyl 1-trifluoromethyl-1-hydroxy-3-oxo-phosphonates, the related (methyl)phosphinates and (phenyl)phosphinates, and phosphine oxides were obtained in good yield via direct phosphonylation of acyltrifluoroacetones with diethyl phosphite, ethyl (methyl)phosphonite, ethyl (phenyl)phosphonite, and diphenyl-phosphine oxide in the presence of triethyl borate. The subsequent dehydration of the selected phosphonates and phosphinates proceeds smoothly affording previously unknown diethyl 1,2-unsaturated 1-trifluoromethyl-3-oxophosphonates, ethyl 1-trifluoro-methyl-3-oxo(methyl)-, and ethyl 1-trifluoromethyl-3-oxo(phenyl) phosphinates in good yields.

Key words

acyltrifluoroacetones - phosphonylation - triethyl borate - fluorinated phosphonate - fluorinated phosphinate - fluorinated phosphine oxides

References and Notes

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13

Typical Procedure for the Preparation of Compounds 4-7 A mixture of diketone 3 (10.0 mmol), phosphorus reagent [11.0 mmol in the case of diethyl phosphite or ethyl(methyl)phosphonite, 15 mmol in the case of ethyl(phenyl)phosphonite, or 20 mmol in the case of diphenylphosphine oxide], and triethylborate (1.60 g, 11.0 mmol in the case of phosphite and phosphonites or 2.92 g, 20.0 mmol in the case of diphenylphosphine oxide) was refluxed in MeCN (20 mL) for the respective time (Table  [¹] ). All volatile materials were removed in vacuo, and the residue was dissolved in Et₂O (30 mL). The ether solution was washed with H₂O (10 mL) and 10% solution of Na₂CO₃ (3 × 10 mL). For compounds 6 and 7 a sat. solution of NaHCO₃ was used. Et₂O was removed, the crude product was dissolved in CHCl₃ (10 mL) and filtered through a layer of silica (3 sm). The solvent was evaporated, and the residue was dried in vacuo for 12 h. For compounds 6 and 7, the products were purified by column chromatography (EtOAc-hexane = 1:2).
Data for Diethyl 1-Hydroxy-3-(4-nitrophenyl)-3-oxo-1-(trifluoromethyl)propylphosphonate (4b)
Yellowish viscous oil. ^¹H NMR (200 MHz, CDCl₃): δ = 1.23 (t, 3 H, Me, J = 7.1 Hz), 1.27 (t, 3 H, Me, J = 7.1 Hz), 3.21 (dd, 1 H, J _Ha-Hb = 16.1 Hz, J _Ha-P = 18.6 Hz, CHH), 3.82 (dd, 1 H, J _Ha-Hb = 16.1 Hz, J _Hb-P = 7.3 Hz, CHH), 4.10-4.36 (m, 4 H, 2 OCH₂), 6.74 (d, 1 H, J _H-P = 8.3 Hz, OH) 7.61-7.66 (m, 2 H, Ar), 7.88-7.93 (m, 2 H, Ar). ^¹9F NMR (188 MHz, CDCl₃, C₆F₆): δ = 88.96 (d, J _F-P = 5.2 Hz, CF₃). ^³¹P-^¹H decoupled (81 MHz, CDCl₃, 85% H₃PO₄): δ = 16.68 (q, J _P-F = 5.2 Hz). ^¹³C NMR (50 MHz, CDCl₃) δ = 16.13 (d, ^³ J _C-P = 5.2 Hz, Me), 38.64 (s, CH₂), 63.58 (d, ^² J _C-P = 7.4 Hz, OCH₂), 63.63 (d, ^² J _C-P = 7.4 Hz, OCH₂), 75.58 (dq, ^¹ J _C-P = 164.6 Hz, ^² J _C-F = 29.0 Hz), 124.41 (qd, CF₃, ^¹ J _C-F = 285.4 Hz, ^² J _C-P = 12.6 Hz), 124.42, (CH, Ar), 130.87 (CH, Ar), 143.03 (Ar), 150.70 (Ar), 195.94 (d, ^³ J _C-P = 8.5 Hz, C=O). Anal. Calcd for C₁₄H₁₇NPF₃O₇: C, 42.12; H, 4.29; F, 14.28. Found: C, 42.31; H, 4.17; F, 14.42.

18

General Procedure for the Preparation of Compounds 8-10
To a vigorously stirred solution of phosphonate 4 or phosphinate 5 or 6 (5.0 mmol) and dry pyridine (0.79 g, 10 mmol) in dry CH₂Cl₂ (20 mL) a solution of TFAA (2.10 g, 10 mmol) in dry CH₂Cl₂ (20 mL) was added dropwise at 0 ˚C. The reaction mixture was stirred for 4 h at the same temperature, warmed to r.t., washed with cold H₂O (ca. 5 ˚C, 3 × 10 mL), and filtered through layer of silica (4 sm). The solvent was evaporated and residue was dried in vacuo for 12 h.
Data for Diethyl 3-(4-Nitrophenyl)-3-oxo-1-(trifluoromethyl)prop-1-enylphosphonate (8b) Yellow viscous oil; E/Z = 10:1.
Compound ( Z )-8b: ^¹H NMR (200 MHz, CDCl₃): δ = 1.27 (t, 6 H, 2 Me, J = 7.1 Hz), 4.01-4.17 (m, 4 H, 2 OCH₂), 7.57 (dq, 1 H, J _H-P = 39.0 Hz, J _H-F = 1.5 Hz, =CH), 8.02-8.06 (m, 2 H, Ar), 8.31-8.36 (m, 2 H, Ar). ^¹9F NMR (188 MHz, CDCl₃, C₆F₆): δ = 99.27 (s). ^³¹P-^¹H coupled (81 MHz, CDCl₃, 85% H₃PO₄): δ = 6.67 (dm, J _P-H = 39.0 Hz). ^³¹P-^¹H decoupled (81 MHz, CDCl₃, 85% H₃PO₄): δ = 6.67 (q,
J _P-F = 2.5 Hz). ^¹³C NMR (50 MHz, CDCl₃): δ = 16.00 (d, ^³ J _C-P = 7.1 Hz, Me), 63.80 (d, ^² J _C-P = 5.7 Hz, OCH₂), 121.65 (qd, CF₃, ^¹ J _C-F = 275.5 Hz, ^² J _C-P = 15.5 Hz), 124.06 (CH, Ar), 129.00 (dq, ^¹ J _C-P = 182.3 Hz, ^² J _C-F = 32.5 Hz), 129.82, (CH, Ar), 139.48 (Ar), 147.39 (m, =CH), 150.82 (Ar), 190.20 (d, ^³ J _C-P = 7.1 Hz, C=O).
Compound ( E )-8b: ^¹H NMR (200 MHz, CDCl₃): δ = 1.41 (t, 6 H, 2 Me, J = 7.1 Hz), 4.19-4.35 (m, 4 H, 2 OCH₂), 7.77 (d, 1 H, J _H-P = 24.0 Hz, =CH), 8.02-8.06 (m, 2 H, Ar), 8.31-8.36 (m, 2 H, Ar). ^¹9F NMR (188 MHz, CDCl₃, C₆F₆): δ = 104.36 (d, J _F-P = 5.5 Hz). ^³¹P-^¹H decoupled (81 MHz, CDCl₃, 85% H₃PO₄): δ = 9.06 (q, J _P-F = 5.2 Hz). ^¹³C NMR (50 MHz, CDCl₃): δ = 16.20 (d, ^³ J _C-P = 7.0 Hz, Me), 64.09 (d, ^² J _C-P = 5.7 Hz, OCH₂), 124.26 (CH, Ar), 130.04, (CH, Ar), 148.66 (m, =CH). Signals of carbon without hydrogen were not found. Anal. Calcd for C₁₄H₁₅NPF₃O₆: C, 44.11; H, 3.97; F, 14.95. Found: C, 44.03; H, 3.75; F, 15.10.