A New Synthesis of Alkylidenecyclopropanes by the Julia-Lythgoe-type Olefination Using Sulfones and Sulfoxides

Abstract

The first use of the Julia-Lythgoe-type olefination with cyclopropylsulfones and cyclopropylsulfoxides for the synthesis of alkylidenecyclopropanes is reported.

Key words

olefination - carbocycles - sulfones - sulfoxides - alkylidenecyclopropanes

References

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27

Typical Procedure for the Reductive Elimination of the Sulfones with Na/Hg.
To a stirred suspension of sodium amalgam (10%, 422 mg, 1.85 mmol) in THF (6 mL) and MeOH (2 mL) at -20 °C, under Argon was added a solution of the appropriate cyclopropylsulfone (0.37 mmol) in THF (2 mL). After 30 min at same temperature the reaction mixture was diluted with Et₂O, washed with brine, dried and concentrated in vacuo. Chromatography with light petroleum-Et₂O, (1:1) yielded the corresponding alkylidenecyclopropanes.
Typical Procedure for the Reductive Elimination of the Sulfones with Mg/HgCl ₂ cat.
A mixture of the cyclopropylsulfone (0.76 mmol), Mg powder (54.7 mg, 2.28 mmol) and few crystals of HgCl₂ in dry EtOH (10 mL) was stirred for 1 h at r.t. The reaction mixture was then poured into cold 0.5 N HCl and extracted with Et₂O. The organic layer was washed with sat. aq NaHCO₃, dried (Na₂SO₄), filtered and then concentrated in vacuo to give the crude products which were purified as above.
Typical Procedure for the Reductive Elimination of the Sulfoxides with n -BuLi.
To a solution of n-BuLi (1.5 M in hexane, 1.6 mL, 2.4 mmol) at -78 °C, under an argon atmosphere, a solution of the cyclopropylsulfoxide (0.6 mmol) in THF (10 mL) was added dropwise with stirring. After stirring for 5 min, the reaction was quenched with sat. aq NH₄Cl and the mixture was extracted with Et₂O. The organic layer, dried and evaporated, gave the corresponding alkylidenecyclo-propanes that were purified as above.
All new compounds have been fully characterized by ¹H NMR (300 MHz), ¹³C NMR (75.4 MHz), IR, GLC mass spectra (70 eV) and elemental analyses.
Selected analytical data for some representative derivatives are reported.
Cyclopropyl carbinol 1d: A 65:35 mixture of two diastereoisomers. Minor isomer. White crystals, mp 58-60 °C. Yield: 21%. [α]_D ²⁵ +39.30 (c 3.89, CHCl₃). IR (film): 3400 cm^-1.¹H NMR (CDCl₃): δ = 0.91-1.30 (m, 4 H), 1.34 (s, 3 H), 1.39 (s, 3 H), 2.62 (br s, 1 H), 3.49 (d, 1 H, J = 5.1 Hz), 3.78 (t, 1 H, J = 8.1 Hz), 4.04 (dd, 1 H, J = 8.1 Hz and 6.6 Hz), 4.43 (q, 1 H, J = 6.6 Hz), 7.12-7.46 (m, 5 H). ¹³C NMR (CDCl₃): δ = 11.3, 13.9, 25.2, 26.4, 26.8, 66.8, 73.4, 77.5, 109.1, 125.7, 128.1, 128.7, 136.1. MS: m/z (%) = 280 (13) [M⁺], 265 (15), 207(10), 191 (13), 178 (14), 149 (13), 101(100), 91(16). Anal. Calcd for C₁₅H₂₀O₃S: C, 64.26; H, 7.19; S, 11.43. Found: C, 64.41; H, 7.26; S, 11.39. Major isomer. Yellow oil. Yield 40%. [α]_D ²⁷ -25.74 (c 4.00, CHCl₃). IR (neat): 3430 cm^-1. ¹H NMR (CDCl₃): δ = 0.93-1.28 (m, 4 H), 1.31 (s, 3 H), 1.38 (s, 3 H), 2.65 (br s, 1 H), 3.51 (d, 1 H, J = 5.7 Hz), 3.91 (dd, 1 H, J = 6.3 Hz and J = 8.4 Hz), 4.04 (dd, 1 H, J = 8.4 Hz and 6.3 Hz), 4.31 (q, 1 H, J = 6.3 Hz), 7.12-7.48 (m, 5 H). ¹³C NMR (CDCl₃): δ = 13.3, 13.6, 25.1, 26.1, 27.3, 65.5, 75.0, 78.7, 108.5, 125.6, 128.1, 128.5, 136.0. MS: m/z (%) = 280 (14) [M⁺], 265 (20), 204 (4), 191(23), 179 (20), 149 (14), 101(100), 91(15). Anal. Calcd for C₁₅H₂₀O₃S: C, 64.26; H, 7.19; S, 11.43. Found: C, 64.36; H, 7.28; S, 11.34.
Sulfoxide 8d: (Obtained by oxidation of the minor isomer of 1d): Colorless oil. Yield 90%. Spectral data refer to a 70:30 mixture of two inseparable diastereoisomers. IR (neat): 1040, 3430 cm^-1. ¹H NMR (CDCl₃): δ = 0.98 (s, 3 H), 1.18-1.57 (m, 8 H), 1.22 (s, 3 H), 1.27 (s, 3 H), 1.43 (s, 3 H), 1.84 (s, 2 H), 3.64-4.29 (m, 8 H), 7.51-7.70 (m, 10 H). Major isomer: MS: m/z (%) = 281 (39) [M⁺ - 15], 221 (18), 195 (100), 153 (77), 125 (34), 109 (18), 101(59), 95 (64), 77 (25). Minor isomer: MS: m/z (%) = 281 (34) [M⁺ - 15], 221 (18), 195 (100), 153 (77), 125 (40), 109 (21), 101 (86), 95 (98), 77 (30). Anal. Calcd for C₁₅H₂₀O₄S: C, 60.79; H, 6.80; S, 10.82. Found: C, 60.64; H, 6.68; S, 10.61.
Acetate 9d: Yield 90%. A 70:30 mixture of two inseparable diastereoisomers: IR (neat): 1060, 1740 cm^-1. Major isomer: ¹H NMR (CDCl₃): δ = 1.20-1.36 (m, 4 H), 1.30 (s, 3 H,), 1.34 (s, 3 H), 1.84 (s, 3 H), 3.73 (dd, 1 H, J = 6.3 Hz and J = 8.7 Hz), 4.07 (dd, 1 H, J = 6.3 Hz and J = 8.7 Hz), 4.48 (q, 1 H, J = 6.3 Hz), 4.85 (d, 1 H, J = 6.9 Hz), 7.47-7.70 (m, 5 H). Minor isomer: ¹H NMR (CDCl₃): δ = 1.20-1.36 (m, 4 H), 1.28, (s, 3 H), 1.32 (s, 3 H), 1.83 (s, 3 H), 3.78 (dd, 1 H, J = 6.3 Hz and J = 8.7 Hz), 4.02 (dd, 1 H, J = 6.3 Hz and J = 8.7 Hz), 4.39 (q, 1 H, J = 6.3 Hz), 5.03 (d, 1 H, J = 6.3 Hz), 7.47-7.70 (m, 5 H). MS (identical for the two isomers): m/z (%) = 323 (7) [M⁺ - 15], 281 (6), 207 (43), 191 (12), 153 (27), 125 (13), 95 (59), 43 (100). Anal. Calcd for C₁₇H₂₂O₅S: C, 60.34; H, 6.55; S, 9.47. Found: C, 60.44; H, 6.78; S, 9.61.
Methylcyclopropilidene 15b: Colorless oil. Yield 65%_. Data worked out from the unseparable 60:40 E/Z-mixture: ¹H NMR (CDCl₃): δ = 1.05-1.12 (m, 2 H), 1.63-1.70 (m, 2 H), 1.76-1.80 (m, 3 H, E-isomer), 1.84-1.89 (m, 3 H, Z-isomer), 2.29 (s, 3 H, Z-isomer), 2.30 (s, 3 H, E-isomer), 2.52-2.55 (m, 2 H), 5.91-5.95 (m, 2 H), 6.98-7.08 (m, 8 H). ¹³C NMR (CDCl₃): δ = 13.3, 15.0, 16.8, 17.0, 19.2, 19.7, 19.8, 20.9, 21.0, 114.3, 114.5, 126.1, 126.3, 128.9, 129.0, 135.0, 135.1, 139.2, 139.5. MS (identical for the two isomers): m/z (%) = 158 (12) [M⁺], 143 (100), 128 (65), 115 (25), 91 (7), 77 (12). Anal. Calcd for C₁₂H₁₄: C, 91.08; H, 8.92. Found: C, 91.15; H, 8.98.
Compound 16b: A 50:50 mixture of two E-diastereoisomers (syn + anti). Colorless oil. Yield 20%. IR (neat): 3400 cm^-1. anti-Diastereoisomer: ¹H NMR (CDCl₃): δ = 0.85-0.90 (m, 2 H), 1.24-1.26 (m, 1 H), 1.34 (d, 3 H, J = 5.7 Hz), 1.57 (br s, 1 H), 1.75-1.78 (m, 1 H), 2.30 (s, 3 H), 3.36 (q, 1 H, J = 5.7 Hz), 6.95-7.08 (m, 4 H). ¹³C NMR (CDCl₃): δ = 13.6, 20.9, 22.7, 30.6, 71.9, 76.6, 125.8, 129.0, 135.2, 139.3. syn-Diastereoisomer: ¹H NMR (CDCl₃): δ = 0.91-0.98 (m, 2 H), 1.20-1.22 (m, 1 H), 1.32 (d, 3 H, J = 5.7 Hz), 1.57 (br s, 1 H), 1.84-1.92 (m, 1 H), 2.30 (s, 3 H), 3.34 (q, 1 H, J = 5.7 Hz), 6.95-7.08 (m, 4 H). ¹³C NMR (CDCl₃): δ = 13.1, 20.4, 22.3, 30.6, 71.9, 76.6, 125.7, 129.0, 135.1, 139.4. MS (identical for the two isomers): m/z (%) = 176 (5) [M⁺], 143 (21), 131 (40), 121 (96), 117 (100), 91 (55), 77 (20). Anal. Calcd for C₁₂H₁₆O: C, 81.77; H, 9.15. Found: C, 81.65; H, 8.86.