CuX₂-Mediated Halogenation of Alkylidenecyclopropanes: A Highly Efficient and Stereoselective Method for the Preparation of Z-2, 4-Dihalobutenes

Abstract

A convenient and efficient method for the synthesis of (Z)-2,4-dihalobutenes, a useful building block in organic synthesis, was reported in good yield by the reaction of alkylidenecyclopropane­s and CuX₂ (or CuI/I₂).

Key words

copper-mediated - halogenation - alkylidenecyclo­propane - stereoselective - (Z)-2,4-dihalobutene

References

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7

General Procedure for the Synthesis of 2: Condition A:
A solution of 1a (130 mg, 1.0 mmol) with CuBr₂ (450 mg, 2.0 mmol) in 5 mL of CH₃CN was stirred at 65 °C for 14 h. The mixture was then diluted with 30 mL of sat. NH₄Cl and extracted three times with n-hexane. The organic phases were combined and dried over MgSO₄. After evaporation, the residues were purified via chromatography on silica gel with n-hexane as the eluent to afford 254 mg (82%) of 2a. Condition B. A solution of 1a (130 mg, 1.0 mmol) with I₂ (510 mg, 2.0 mmol) and CuI (20 mg, 0.1 mmol) in 10 mL of CH₃CN was stirred at 65 °C for 16 h. The mixture was then diluted with 30 mL of sat. Na₂S₂O₃ and extracted three times with n-hexane. The organic phases were combined and dried over MgSO₄. After evaporation, the residues were purified via chromatography on silica gel with n-hexane as the eluent to afford 349 mg (91%) of 2c.

8

Selected Data of Compounds 2c and 2g: (a)Spectral and analytical data for 2c: IR(neat): 1491 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.48-7.46 (m, 2 H), 7.37-7.31 (m, 3 H), 6.80 (s, 1 H), 3.41-3.38 (t, J = 7.0 Hz, 2 H), 3.16-3.12 (t, J = 7.0 Hz, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 137.9, 136.9, 128.6, 128.2, 128.1, 105.0, 49.9, 5.18. MS (EI): m/z (%) = 384 (21.41) [M⁺], 257 (12.16), 130(100). Anal. Calcd for C₁₀H₁₀I₂: C, 31.28; H, 2.62. Found: C, 31.55; H, 2.39.
(b)Spectral and analytical data for 2g: IR(neat): 1504 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.36-7.32 (m, 52 H), 7.28-7.21 (m, 3 H), 3.80& ndash;3.77 (t, J = 6.8 Hz, 2 H), 2.98-2.95 (t, J = 6.8 Hz, 2 H), 2.09 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 142.5, 135.5, 128.6, 128.3, 127.4, 125.7, 42.4, 39.0. MS (EI): m/z (%) = 217 (1.98) [M⁺ + 3], 216 (16.67) [M⁺ + 2], 215 (3.93) [M⁺ + 1], 214 (25.64) [M⁺], 129(100). Anal Calcd for C₁₁H₁₂Cl₂: C, 61.42; H, 5.62. Found: C, 61.71; H, 5.88.