Carbomagnesiation of Acetylenic Sulfones Catalyzed by CuCN and its Application in the Stereoselective Synthesis of Polysubstituted Vinyl Sulfones

Abstract

Polysubstituted vinyl sulfones were prepared stereoselectively by the carbomagnesiation of acetylenic sulfones in the presence of Cu(I). Bisubstituted vinyl sulfones were obtained by the carbomagnesiation of acetylenic sulfones followed by hydrolysis. Trisubstituted vinyl sulfones were obtained by the carbomagnesiation of acetylenic sulfones followed by reacting with other electrophiles.

Key words

carbomagnesiation - acetylenic sulfone - vinyl sulfone - 1,4-dienes - conjugated enynes

References

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12

Crystal Data for 3a: C₂₁H₁₈O₂S, MW = 334.41, monoclinic, space group P2₁/n, a = 12.8256(6), b = 5.8678(7), c = 23.871(3) Å; α = 90°, β = 105.360(3)°, γ = 90°. V = 1732.3(4) ų, T = 293 K, Z = 4, D _c = 1.282 gcm^-1, µ = 0.196 mm^-1, λ = 0.71073 Å; F(000) 704, 4060 independent reflections (R _int = 0.0848), 10150 reflections collected; refinement method, Full - matrix least - squares on F ^² ; goodness of fit on F ^² = 0.623; Final R indices [I>2σ(I)] R ₁ = 0.0427, wR ₂ = 0.0461.

15

Crystal Data for 4f: C₂₅H₂₄O₂S, MW = 388.50, monoclinic, space group P2₁/n, a = 5.9754(5), b = 22.733(2), c = 15.3647(3) Å; α = 90°, β = 92.512(2)°, γ = 90°. V = 2085.1(3) ų, T = 293 K, Z = 4, D _c = 1.238 gcm^-1, µ = 0.173 mm^-1, λ = 0.71073 Å; F(000) 824, 4772 independent reflections (R _int = 0.1229), 12695 reflections collected; refinement method, Full - matrix least - squares on F ^² ; goodness - of - fit on F ^² = 0.879; Final R indices [ I>2σ(I)] R ₁ = 0.0545, wR ₂ = 0.1176.

16

General Procedure for the Reaction of Acetylenic Sulfone and PhMgBr, Synthesis of 1-Diphenyl-2-( p -tolylsulfonyl)ethene ( 3a). To the solution of PhMgBr (0.6 mmol) in THF-CH₂Cl₂ (1:4, 5 mL) was added CuCN (10 mol%) and 1-phenyl-2-(p-tolylsulfonyl)ethyne (0.5 mmol) at -20 °C with stirring. The reaction mixture was stirred at
-20 °C for 30 min. Then the reaction was quenched with sat. NH₄Cl and extracted with CH₂Cl₂. The organic phase was washed with sat. brine and dried over MgSO₄. After filtration and removal of the solvent in vacuo, the crude product was purified with flash chromatography (silica/hexanes-EtOAc, 10:1) and the desired adduct 1, 1-diphenyl-2-(p-tolylsulfonyl)ethene (3a) was obtained as colorless crystal. Mp 101 °C (from hexanes-EtOAc) (Lit. [18] 102-103 °C). ¹H NMR (400 MHz, CDCl₃): δ = 7.47 (d, J = 8.24 Hz, 2 H), 7.37-7.35 (m, 7 H), 7.31-7.27 (m, 2 H), 7.14 (d, J = 7.96 Hz, 1 H), 7.10-7.08 (m, 2 H), 6.99 (s, 1 H), 2.37 (s, 3 H). IR (KBr): 1326, 1142 cm^-1. MS (EI): m/z (%) = 335 (46) [M⁺ + 1], 178 (100).

17

General Procedure for the Reaction of Acetylenic Sulfone and PhMgBr and further Reaction with Allyl Bromide or Alkynyphenylliodonium Tosylate. To the solution of PhMgBr (0.6 mmol) in THF-CH₂Cl₂ (1:4, 5 mL) was added CuCN (10 mol%) and acetylenic sulfone (0.5 mmol) at -20 °C with stirring. After the addition completed (monitored by TLC), allyl bromide or alkynylphenyl iodonium tosylate (0.8 mmol) was added. The reaction mixture was stirred at -20 °C for 2-2.5 h. Then the reaction was quenched with sat. NH₄Cl and extracted with CH₂Cl₂. After usual workup, the desired adduct 4 or 5 was obtained. Product 1,1-diphenyl-2-(p-tolylsulfonyl)-1,4-pentadiene (4a): Mp 136 °C (from hexanes/ethyl acetate). ¹H NMR (400 MHz, CDCl₃): δ = 7.30-7.24 (m, 5 H), 7.17-7.15 (m, 1 H), 7.12-7.10 (m, 4 H), 7.08-7.04 (m, 2 H), 6.97-6.95 (m, 2 H), 6.04-5.91 (m, 1 H), 5.11-5.00 (m, 2 H), 3.35 (d, J = 6.32 Hz, 2 H), 2.35 (s, 3 H). IR (KBr): 3078, 1302, 1145 cm^-1. MS (EI): m/z (%) = 375 (10) [M⁺ + 1], 218 (100). Anal. Calcd for C₂₄H₂₂O₂S: C, 76.97; H, 5.92. Found: C, 76.86; H, 5.88.