The First Synthesis and Reaction of β-Ethoxy-α-fluoro-α-(phenyl­selanyl)ethene: Scandium or Lanthanum Triflate Catalyzed α-Fluoroformylalkenylation of Aldehydes

Abstract

We describe the first preparation of the hitherto unknown β-ethoxy-α-fluoro-α-(phenylselanyl)ethenes and the successful Lewis acid catalyzed α-fluoroformylalkenylation of non-enolizable aldehyde acetals to provide α,β-unsaturated aldehydes or acetals exclusively.

(phenylselanyl)ethane - scandium triflate - lanthanum triflate - double bond formation - fluorine - α,β-unsaturated aldehydes

References

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<A NAME="RU15305ST-11">11</A>

Preparation of β-ethoxy-α-fluoro-α-(phenylselanyl)ethene(4). To a toluene (80 mL) solution of ethyl 2-fluoro-2-(phenylselanyl)acetate (1; 4.00 g, 15.3 mmol) was added DIBAL-H (18.4 mL, 1 M toluene solution, 18.4 mmol) at -78 °C under an Ar atmosphere. After the reaction mixture was stirred for 30 min, 1 M HCl solution (16 mL) was added to the mixture. The resulting mixture was stirred for 10 min and then poured into H₂O (200 mL). The organic layer was separated and the aqueous layer was extracted with Et₂O. The combined organic layer was dried over MgSO₄. The solvent was removed under reduced pressure. To the residue in EtOH (23 mL) was added ethyl orthoformate (11.4 g, 76.6 mmol) and p-TsOH (0.26 g, 1.53 mmol). The mixture was stirred for 12 h at 20 °C and poured into a sat. soln of NaHCO₃ (200 mL). Work-up and purification by column chromatography on silica gel eluting with EtOAc-hexane (1:50) gave 2-fluoro-2-(phenylselanyl)acetaldehyde diethyl acetal(3) (14.1 g, 91%) as a yellow oil. IR: 2978, 2929, 2884, 2362, 2344, 1579, 1478, 1372, 1340, 1301, 1118, 1067, 1023, 999, 891, 741, 691, 470 cm^-1; ¹H NMR: δ = 1.25 (3 H, t, J = 7 Hz, Me), 1.26 (3 H, t, J = 7 Hz, Me), 3.62-3.68 (2 H, m, OCH₂), 3.76-3.82 (2 H, m, OCH₂), 4.71 (1 H, dd, J = 4, 9 Hz, acetal H), 6.02 (1 H, dd, J = 4, 52 Hz, CHF), 7.24-7.33 (3 H, m, ArH), 7.64-7.66 (2 H, m, ArH); ¹⁹F NMR (referenced to CF₃CO₂H): δ = -87.05 (dd, J = 9, 53 Hz); MS: m/z = 292 (M⁺). Anal. Calcd for C₁₂H₁₇FO₂Se: C, 49.49; H, 5.88. Found: C, 49.27; H, 5.79
An ethereal (5.0 mL) solution of 3 (3.0 g, 10.3 mmol)was added to lithium isopropylcyclohexylamide (prepared from isopropylcyclohexylamine (2.90 g, 20.6 mmol) and BuLi (6.0 mL, 15.4 mmol) in Et₂O (60 mL)) at -60 °C. The reaction mixture was warmed to -40 °C and then stirred for 10 min. The mixture was poured into H₂O (200 mL). The organic layer was separated and the aqueous layer was extracted with Et₂O. The combined organic layers were dried over MgSO₄. The solvent was removed under reduced pressure. The residue was purified by flash chromatography on silica gel eluting with EtOAc-hexane (1:100) to give 4 (2.02 g, 80%) as a yellow oil. IR: 3444, 2980, 2357, 1658, 1577, 1477, 1439, 1395, 1313, 1194, 1130, 1061, 1000, 902, 737, 689, 535, 515, 466, 441, 425, 406 cm^-1; ¹H NMR: δ = 1.33 (3 H, t, J = 7 Hz, Me), 3.97 (2 H, q, J = 7 Hz, OCH₂), 6.24 (1 H, d, J = 19 Hz, olefinic H), 7.24-7.30 (3 H, m, ArH), 7.48 (2 H, d, J = 8 Hz, ArH); ¹⁹F NMR: δ = -39.67 (d, J = 18 Hz); MS: m/z = 246 (weak M⁺). Compound 4 was too volatile to measure the elemental analysis.

<A NAME="RU15305ST-12">12</A>

A typical procedure for the preparation of 2-fluoro-4′-methoxycinnamaldehyde dimethyl acetal(6a): Lanthanum triflate (60 mg, 0.10 mmol) was added to a ClCH₂CH₂Cl (5.0 mL) solution of 4 (0.50 g, 2.04 mmol) and p-methoxybenz-aldehyde dimethyl acetal (0.80 g, 4.07 mmol) under an Ar atmosphere. The reaction mixture was refluxed for 10 min, cooled, and treated with Et₃N (2 drops). Work-up afforded 2-fluoro-4′-methoxycinnamaldehyde dimethyl acetal (6a, 0.77 g, 85%).

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