An Improved gem-Dimethylcyclopropanation Procedure Using Triisopropylsulfoxonium Tetrafluoroborate

Abstract

A new procedure for the cyclopropanation of α,β-unsaturated carbonyl compounds and related systems is described which employs triisopropylsulfoxonium tetrafluoroborate and sodium hydride in dimethylformamide. Using this reagent, a range of α,β-unsaturated ketones (and an ester and a vinyl nitro example) has been converted into the corresponding gem-dimethylcyclopropyl carbonyl compounds; in addition, a preliminary result is described in which an activated alcohol is converted directly into a gem-dimethylcyclopropyl ketone by a one-pot tandem oxidation-cyclopropanation sequence, albeit in low yield.

Key words

cyclopropanes - cyclopropanation - tandem oxidation procedures - sulfoxonium salts - ruthenium tetroxide

References and Notes

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18

Preparation of Triisopropylsulfoxonium Tetrafluoroborate
A 250 mL round-bottomed flask with stirrer bar was charged with triisopropylsulfonium tetrafluoroborate [14] (6.20 g, 25.0 mmol, 1.0 equiv), and then MeCN (36 mL), CCl₄ (36 mL), and H₂O (54 mL) were added via syringe. The resulting biphasic solution was stirred vigorously and ruthenium(III) chloride (2.07 g, 10.0 mmol, 0.40 equiv) added in a single portion. The mixture was stirred for 10 min and then NaIO₄ (40.10 g, 187.5 mmol, 7.5 equiv) was added in 5 portions over ca. 5 min to the brown-coloured solution. The flask was loosely stoppered with a cork and the mixture vigorously stirred overnight at r.t. (14 h). The resulting grey-brown heterogeneous suspension was filtered through a Celite^® pad (3 cm × 70 mm Ø) and washed with H₂O (400 mL). The yellow filtrate was stirred vigorously and MeOH (50 mL) added to quench the residual RuO₄. The green suspension was concentrated under reduced pressure to remove the water present (60 °C) and the grey solid residue suspended in acetone (400 mL). The reaction mixture was stirred for a further 10 min and filtered to remove the residual inorganic solids. Concentration of the filtrate under reduced pressure afforded a yellow-orange powder that was recrystallised from MeOH-Et₂O. The crude solid was dissolved in 10 mL of boiling MeOH and Et₂O added until the solution remained turbid. The mixture was then re-heated until homogeneous and allowed to cool, to afford the title compound as colourless plates (5.06 g, 76%); mp 108-109 °C. IR (acetone): ν_max = 3427, 1699, 1642, 1462, 1369, 1235, 1198, 1049 cm^-1. ¹H NMR (400 MHz, acetone-d ₆): δ = 1.79 (d, J = 7.0 Hz, 18 H, CH₃), 4.73 (sept, J = 7.0 Hz, 3 H, CH). ¹³C NMR (100 MHz, acetone-d ₆): δ = 15.7 (CH₃), 53.0 (CH). ¹⁹F NMR (254 MHz, acetone-d ₆): δ = -151.6. ¹¹B NMR (87 MHz, acetone-d ₆): δ = -1.9. ESI-MS: m/z (%) = 177 (100) [M⁺]. HRMS-FAB: m/z calcd for C₉H₂₁OS: 177.1308 (0.4 ppm error); found: 177.1308 [M⁺]. Anal. Calcd for C₉H₂₁BF₄OS: C, 40.93; H, 8.01. Found: C, 40.76; H, 7.85.

19

All known products were characterised by NMR spectroscopy and comparison of key data with those published; novel products were fully characterised.

20

Representative Procedure for Cyclopropanation of α,β-Unsaturated Carbonyl Compounds (Table 1, Entry 1)
A 25 mL round-bottomed flask with stirrer bar was charged with NaH (60% dispersion in mineral oil, 23 mg, 0.57 mmol, 1.2 equiv), sealed with a rubber septum and purged with argon. The flask was maintained under argon and anhyd DMF (4 mL) was added. The vigorously stirred suspension was cooled to 0 °C, the septum briefly removed and triisopropylsulfoxonium tetrafluoroborate (152 mg, 0.57 mmol, 1.2 equiv) added in a single portion. The mixture was stirred for 5 min before the addition of a solution of (E)-chalcone (100 mg, 0.48 mmol) in DMF (1 mL) dropwise by cannula. The cooling bath was removed and the brown-coloured solution allowed to stir at r.t. until the reaction was deemed to be complete by TLC (5 h). The reaction was quenched by the addition of sat. aq NH₄Cl (5 mL), diluted with H₂O (20 mL) and extracted with Et₂O (3 × 15 mL). The combined organic extracts were dried (Na₂SO₄) and the solvent removed in vacuo. The residue was purified by column chromatography (PE-Et₂O, 19:1 ) to afford trans-(2,2-dimethyl-3-phenylcyclopropyl)-phenylmethanone (6) as a cream-coloured solid (109 mg, 91%); mp 63-64 °C. R _f = 0.29 (PE-Et₂O, 19:1). ¹H NMR (400 MHz, CDCl₃): δ = 1.12 (s, 3 H, CH₃), 1.27 (s, 3 H, CH₃), 2.91 (d, J = 6.0 Hz, 1 H, CH), 3.12 (d, J = 6.0 Hz, 1 H, CH), 7.20-7.24 (m, 3 H, ArH), 7.28-7.32 (m, 2 H, ArH), 7.49-7.53 (m, 2 H, ArH), 7.57-7.61 (m, 1 H, ArH),7.99-8.02 (m, 2 H, ArH). Data consistent with those reported in the literature. [6]