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).

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

References

1a Barluenga J. Sanz R. Fananas F. Chem.-Eur. J.  1997,  3:  1324 

1b Sole D. Carcho Y. Llebaria A. Moreto J. Delgado A. J. Org. Chem.  1996,  61:  5895 

1c Sato Y. Honda T. Shibasaki M. Tetrahedron Lett.  1992,  2593 

2a Padwa A. Brodney M. Liu B. Satake K. Wu T. J. Org. Chem.  1999,  64:  3595 

2b Barton T. Lin J. Ijadi-Maghsood S. Power M. Zhang X. Ma Z. Shinrizu H. Gordon M. J. Am. Chem. Soc.  1995,  117:  11695 

3a Nakamura I. Yamamoto Y. Adv. Synth. Catal.  2002,  2:  111 

3b Brandi A. Goti A. Chem. Rev.  1998,  98:  598 

3c Suginome M. Matsuda T. Ito Y. J. Am. Chem. Soc.  2000,  122:  11015 

3d Lautens M. Ren Y. J. Am. Chem. Soc.  1996,  118:  9597 

3e Tsukada N. Shibuya A. Nakamura I. Yamamoto Y. J. Am. Chem. Soc.  1997,  119:  8123 

3f Nakamura I. Saito S. Yamamoto Y. J. Am. Chem. Soc.  2000,  122:  2661 

3g Nakamura I. Siriwardana AI. Saito S. Yamamoto Y. J. Org. Chem.  2002,  67:  3445 

3h Nakamura I. Itagaki H. Yamamoto Y. J. Org. Chem.  1998,  63:  6458 

3i Camacho DH. Oh BH. Nakamura I. Saito S. Yamamoto Y. Tetrahedron Lett.  2002,  43:  2903 

3j Nakamura I. Oh BH. Saito S. Yamamoto Y. Angew. Chem. Int. Ed.  2001,  40:  1298 

3k Lautens M. Ren Y. Delanghe PHM. J. Am. Chem. Soc.  1994,  116:  8821 

3l Oh BH. Nakamura I. Saito S. Yamamoto Y. Tetrahedron Lett.  2001,  42:  6203 

3m Camacho DH. Nakamura I. Saito S. Yamamoto Y. J. Org. Chem.  2001,  66:  270 

3n Lautens M. Ren Y. J. Am. Chem. Soc.  1996,  118:  10668 

3o Corlay H. Lewis RT. Motherwell WB. Shipman M. Tetrahedron  1995,  51:  3303 

3p Camacho DH. Nakamura I. Saito S. Yamamoto Y. Angew. Chem. Int. Ed.  1999,  38:  3585 

3q Lautens M. Meyer C. Lorenz A. J. Am. Chem. Soc.  1996,  118:  10676 

3r Bessmertnykh AG. Blinov KA. Grishin YK. Donskaya NA. Tveritinova EV. Yur’eva NM. Beletskaya IP. J. Org. Chem.  1997,  62:  606 

3s Bassler T. Eymann W. Heyd WE. Kopp R. J. Am. Chem. Soc.  1974,  96:  6686 

3t Salaun J. Hanack M. J. Org. Chem.  1975,  40:  1994 

4a Siriwardana AI. Nakamura I. Yamamoto Y. Tetrahedron Lett.  2003,  985 

4b Xu B. Shi M. Org. Lett.  2003,  5:  1485 

5 Kortmann I. Werstermann B. Synthesis  1995,  931 

6 Baird WC. Surridge JH. Buza M. J. Org. Chem.  1971,  36:  3324 

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.

9 Utimoto K. Tamura M. Sisido K. Tetrahedron  1973,  14:  1169