An Efficient Synthesis of Allenyl Perfluoroalkyl Ketones from Mono-1,2-Addition-Elimination Reaction of Allenoates with R_fMgX

Abstract

An efficient method for the synthesis of perfluoroalkyl allenyl ketones via the 1,2-addition-elimination reaction of per­fluoroalkyl Grignard reagents with allenoates has been established. No further reaction was observed between these perfluoroalkyl ketones and R_fMgX. Under the catalysis of PdCl₂ or AuCl₃, perfluoroalkyl 1,2-allenyl ketones can be transformed to 2-perfluoroalkyl-substituted furans; they may also undergo 1,2-addition with organolithiums to afford tertiary 1,2-allenols containing a perfluoroalkyl group.

Key words

1,2-addition - elimination - allenoates - allenyl ketones - Grignard reagents - cyclization

References and Notes

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14

Perfluoroalkyl iodides are commercially available.

15

Method A
To a dried Schlenk tube were added n-C₄F₉I (0.36 mL, d = 2.01 g/mL, 0.72 g, 2.09 mmol) and anhyd Et₂O (2.5 mL). The resulting mixture was cooled to -80 ˚C in a cooling bath and a solution of EtMgBr (0.47 mL, 3.0 M in Et₂O, 1.41 mmol) was added dropwise at -80 ˚C with stirring. After the addition, anhyd Et₂O (0.7 mL) was used to rinse the remaining EtMgBr. The resulting mixture was stirred for 70 min at this temperature. A solution of 1b (81.0 mg, 0.40 mmol) in anhyd Et₂O (1 mL) was added dropwise at -80 ˚C with stirring. Then the mixture was allowed to warm up to
-70 ˚C within 30 min and stirred at -70 ˚C for 6 h. The mixture was quenched with 5 mL of a sat. aq NH₄Cl solution at -70 ˚C. After being warmed up to r.t. naturally, the mixture was extracted with Et₂O (3 × 20 mL). The combined organic extracts were washed with brine (5 mL) and dried over anhyd Na₂SO₄. Filtration, evaporation, and chromatography on silica gel [eluent: petroleum ether (bp 60-90 ˚C)] afforded 2a (111.0 mg, 74%) as a liquid. ^¹H NMR (300 MHz, CDCl₃): δ = 7.42-7.23 (m, 5 H), 6.69 (q, J = 2.6 Hz, 1 H), 2.03 (d, J = 2.6 Hz, 3 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 217.1, 183.4 (t, J = 23.9 Hz), 130.6, 129.0, 128.5, 127.7, 102.8, 98.8, 14.5. ^¹9F NMR (282 MHz, CDCl₃): δ = -80.6 to -81.2 (m, 3 F), -113.5 to -114.0 (m, 2 F), -121.7 to -122.3 (m, 2 F), -125.1 to -125.7 (m, 2 F). MS (EI, 70 ev): m/z (%) = 377 (3.89) [M⁺ + 1], 376 (24.69) [M⁺], 129 (100). IR (neat): 3068, 3035, 2933, 1936, 1700, 1601, 1498, 1462, 1354, 1306, 1240, 1137, 1065, 1048, 1004 cm^-¹. HRMS: m/z calcd for C₁₅H₉F₉O: 376.0510; found: 376.0517.
Method B
To a dried Schlenk tube were added n-C₆F₁₃I (0.45 mL, d = 2.06 g/mL, 0.93 g, 2.09 mmol) and anhyd Et₂O (2.5 mL). The resulting mixture was cooled to -80 ˚C in a cooling bath, and a solution of PhMgBr (0.48 mL, 3.0 M in Et₂O, 1.44 mmol) was added dropwise at -80 ˚C with stirring within 5 min. After the addition, anhyd Et₂O (0.7 mL) was used to rinse the remaining PhMgBr. Then, the resulting mixture was stirred for 85 min at this temperature. A solution of 1b (80.3 mg, 0.40 mmol) in anhyd Et₂O (1 mL) was added dropwise at -80 ˚C with stirring. Then the mixture was allowed to warm up to -70 ˚C within 30 min and stirred at
-70 ˚C for 16 h. The mixture was quenched with a sat. aq NH₄Cl solution (5 mL) at -70 ˚C. After being warmed up to r.t. naturally, the mixture was extracted with Et₂O (3 × 20 mL). The combined organic extracts were washed with brine (5 mL) and dried over anhyd Na₂SO₄. After filtration, evaporation of the solvent, chromatography on silica gel [eluent: petroleum ether (bp 60-90 ˚C)] afforded 2b [132.1 mg, 70%, eluent: petroleum ether (bp 60-90 ˚C)] as a yellow liquid. ^¹H NMR (300 MHz, CDCl₃): δ = 7.44-7.24 (m, 5 H), 6.69 (m, 1 H), 2.03 (d, J = 2.3 Hz, 3 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 217.1, 183.4 (t, J = 23.9 Hz), 130.5, 129.0, 128.5, 127.7, 102.8, 98.7, 14.6. ^¹9F NMR (282 MHz, CDCl₃): δ = -80.8 to -81.0 (m, 3 F), -113.5 to -113.8 (m, 2 F), -121.1 to -121.7 (m, 4 F), -122.7 to -123.1 (m, 2 F), -126.1 to -126.4 (m, 2 F). MS (EI, 70 ev): m/z (%) = 477 (4.78) [M⁺ + 1], 476 (25.60) [M⁺], 129 (100). IR (neat): 3035, 2934, 1936, 1703, 1600, 1498, 1461, 1364, 1315, 1240, 1205, 1145, 1071, 1015 cm^-¹. HRMS: m/z calcd for C₁₇H₉F₁₃O: 476.0446; found: 476.0447.

17

4-Allyl-3-methyl-2-( n -perfluorobutyl)-5-phenylfuran (8a) To a reaction tube was added 2a (76.2 mg, 0.20 mmol), allyl bromide (128.2 mg, 1.0 mmol, purity: 97%), DMA (2 mL), and PdCl₂ (2.2 mg, 0.01 mmol) at r.t. Then the resulting mixture was stirred at 50 ˚C for 20.5 h as monitored by TLC (PE). After the reaction was complete, the mixture was quenched with H₂O (5 mL). The aqueous layer was extracted with Et₂O (5 × 15 mL) and dried over anhyd Na₂SO₄. Filtration, evaporation, and chromatography on silica gel (eluent: n-hexane) of the crude product afforded 8a (69.8 mg, 83%) as a colorless liquid. ^¹H NMR (300 MHz, CDCl₃): δ = 7.64-7.55 (m, 2 H), 7.47-7.31 (m, 3 H), 6.10-5.94 (m, 1 H), 5.21-5.11 (m, 1 H), 5.07-4.95 (m, 1 H), 3.40-3.32 (m, 2 H), 2.12 (t, J = 2.3 Hz, 3 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 152.3, 134.6, 134.4 (t, J = 29.6 Hz), 130.0, 128.7, 128.4, 127.8, 126.3, 119.6, 116.1, 27.8, 8.0. ^¹9F NMR (282 MHz, CDCl₃): δ = -80.9 to -81.2 (m, 3 F), -110.9 to -111.2 (m, 2 F), -123.8 to -124.1 (m, 2 F), -126.3 to -126.6 (m, 2 F). MS (EI, 70 ev): m/z (%) = 417 (8.38) [M⁺ + 1], 416 (43.60) [M⁺], 247 (100). IR (neat): 3085, 3064, 2930, 1640, 1582, 1494, 1448, 1415, 1352, 1236, 1206, 1135, 1101, 1075, 1030
cm^-¹. HRMS: m/z calcd for C₁₈H₁₃F₉O: 416.0823; found: 416.0822.

19

3-Methyl-2- n -perfluorobutyl-5-phenylfuran (8b) To a dried Schlenk tube was added 2a (112.1 mg, 0.30 mmol), anhyd CH₂Cl₂ (1.5 mL), and AuCl₃ (4.5 mg, 5 mol%) under the atmosphere of N₂ at r.t. The resulting mixture was stirred for 24 h at r.t. as monitored by TLC (petroleum ether) followed by the addition of Et₂O (20 mL). Evaporation and purification by flash chromatography on silica gel [eluent: petroleum ether (bp 60-90 ˚C)] afforded 8b (103.4 mg, 92%) as a colorless liquid. ^¹H NMR (300 MHz, CDCl₃): δ = 7.72-7.62 (m, 2 H), 7.45-7.27 (m, 3 H), 6.56 (s, 1 H), 2.21 (t, J = 2.4 Hz, 3 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 155.8, 134.8 (t, J = 31.7 Hz), 129.4, 128.8, 128.7, 127.6, 124.4, 109.4, 10.0. ^¹9F NMR (282 MHz, CDCl₃): δ = -80.9 to -81.2 (m, 3 F), -110.9 to -111.1 (m, 2 F), -123.8 to
-124.1 (m, 2 F), -126.3 to -126.6 (m, 2 F). MS (EI, 70 ev): m/z (%) = 377 (7.99) [M⁺ + 1], 376 (48.23) [M⁺], 207 (100). IR (neat): 3039, 2939, 1626, 1551, 1488, 1451, 1401, 1351, 1236, 1206, 1135, 1087, 1056, 1005 cm^-¹. HRMS: m/z calcd for C₁₅H₉F₉O: 376.0510; found: 376.0509.