CuI/l-Proline-Catalyzed Coupling Reactions of Vinyl Bromides with Activated Methylene Compounds

Abstract

The Ullmann-type coupling reaction of vinyl bromides and activated methylene compounds under CuI/l-proline in DMSO, at 90 °C in the presence of Cs₂CO₃ gives the corresponding vinyl compounds in moderate to good yields. This is a good method for preparing compounds with multiple functional groups including double bonds, carbonyls, and/or esters.

carbon-carbon coupling reaction - Ullmann-type reaction - activated methylene compounds - copper iodide - vinyl bromide

References and Notes

1a Lorsbach BA. Kurth MJ. Chem. Rev.  1999,  99:  1549 

1b Sammelson RE. Kurth MJ. Chem. Rev.  2000,  101:  137 

1c Dilman AD. Ioffe SL. Chem. Rev.  2003,  103:  733 

1d Casiraghi G. Zanardi F. Appendino G. Rassu G. Chem. Rev.  2000,  100:  1929 

1e Luh T.-Y. Leung M.-K. Wong K.-T. Chem. Rev.  2000,  100:  3187 

1f Li C.-J. Chem. Rev.  2005,  105:  3095 

1g Fagnou K. Lautens M. Chem. Rev.  2003,  103:  169 

1h Svedendahl M. Hult K. Berglund P. J. Am. Chem. Soc.  2005,  127:  17988 

1i Fillion E. Carson RJ. Trépanier VE. Goll JM. Remorova AA. J. Am. Chem. Soc.  2004,  126:  15354 

2a Jørgensen M. Lee S. Liu X. Wolkowski JP. Hartwig JF. J. Am. Chem. Soc.  2002,  124:  12557 

2b You J. Verkade JG. Angew. Chem. Int. Ed.  2003,  42:  5051 

2c You J. Verkade JG. J. Org. Chem.  2003,  68:  8003 

2d Beare NA. Hartwig JF. J. Org. Chem.  2002,  67:  541 

2e Stauffer SR. Beare NA. Stambuli JP. Hartwig JF. J. Am. Chem. Soc.  2001,  123:  4641 

2f Fox JM. Huang X. Chieffi A. Buchwald SL. J. Am. Chem. Soc.  2000,  122:  1360 

2g Moradi WA. Buchwald SL. J. Am. Chem. Soc.  2001,  123:  7996 

2h Terao Y. Fukuoka Y. Satoh T. Miura M. Nomura M. Tetrahedron Lett.  2002,  43:  101 

2i Lloyd-Jones GC. Angew. Chem. Int. Ed.  2002,  41:  953 

2j Kashin AN. Mitin AV. Beletskaya IP. Wife R. Tetrahedron Lett.  2002,  43:  2539 

2k Hamada T. Chieffi A. Åhman J. Buchwald SL. J. Am. Chem. Soc.  2002,  124:  1261 

2l Viciu MS. Germaneau RF. Nolan SP. Org. Lett.  2002,  4:  4053 

3a Hassan J. Sévignon M. Gozzi C. Schulz E. Lemaire M. Chem. Rev.  2002,  102:  1359 

3b Ley SV. Thomas AW. Angew. Chem. Int. Ed.  2003,  42:  5400 

3c Kunz K. Scholz U. Ganzer D. Synlett  2003,  2428 

3d Hennessy EJ. Buchwald SL. Org. Lett.  2002,  4:  269 

3e Ma D. Liu F. Chem. Commun.  2004,  1934 

3f Zhang S. Zhang D. Liebeskind LS. J. Org. Chem.  1997,  62:  2312 

3g Bates CG. Saejueng P. Venkataraman D. Org. Lett.  2004,  6:  1441 

3h Jiang Y. Wu N. Wu H. He M. Synlett  2005,  2731 

4a Hurtley WRH. J. Chem. Soc.  1929,  1870 

4b Bruggink A. Ray SJ. McKillop A. Org. Synth.  1978,  58:  52 

4c Bryson TA. Stewart JJ. Gibson JM. Thomas PS. Berch JK. Green Chem.  2003,  5:  174 

4d Bruggink A. McKillop A. Tetrahedron  1975,  31:  2607 

4e Lindley J. Tetrahedron  1984,  40:  1433 

4f Shinkwin AE. Whish WJD. Threadgill MD. Bioorg. Med. Chem.  1999,  7:  297 

5a Hang HC. Drotleff E. Elliott GI. Ritsema TA. Konopelski JP. Synthesis  1999,  398 

5b Suzuki H. Yi Q. Inoue J. Kusume K. Ogawa T. Chem. Lett.  1987,  887 

5c Suzuki H. Kobayashi T. Osuka A. Chem. Lett.  1983,  589 

6 Okuro K. Furuune M. Miura M. Nomura M. J. Org. Chem.  1993,  58:  7606 

7a Ma D. Cai Q. Xie X. Synlett  2005,  1767 

7b Zhu W. Ma D. J. Org. Chem.  2005,  70:  2696 

7c Cai Q. Zhu W. Zhang H. Zhang Y. Ma D. Synthesis  2005,  496 

7d Ma D. Cai Q. Zhang H. Org. Lett.  2003,  5:  2453 

7e Ma D. Cai Q. Org. Lett.  2003,  5:  3799 

7f Ma D. Cai Q. Synlett  2004,  128 

7g Pan X. Cai Q. Ma D. Org. Lett.  2004,  6:  1809 

7h Zhu W. Ma D. Chem. Commun.  2004,  888 

7i Zhang H. Cai Q. Ma D. J. Org. Chem.  2005,  70:  5164 

7j Xie X. Cai G. Ma D. Org. Lett.  2005,  7:  4693 

8a Marcoux J.-F. Doye S. Buchwald SL. J. Am. Chem. Soc.  1997,  119:  10539 

8b Kiyomori A. Marcoux JF. Buchwald SL. Tetrahedron Lett.  1999,  40:  2657 

8c Wolter M. Klapars A. Buchwald SL. Org. Lett.  2001,  3:  3803 

8d Klapars A. Antilla JC. Huang X. Buchwald SL. J. Am. Chem. Soc.  2001,  123:  7727 

8e Antilla JC. Buchwald SL. Org. Lett.  2001,  3:  2077 

9 Wang Z. Bao W. Jiang Y. Chem. Commun.  2005,  2849 

10a Wan Z. Jones CD. Koenig TM. Pu YJ. Mitchell D. Tetrahedron Lett.  2003,  44:  8257 

10b Willis MC. Taylor D. Gillmore AT. Chem. Commun.  2003,  2222 

10c Nordmann G. Buchwald SL. J. Am. Chem. Soc.  2003,  125:  4978 

11

Typical Procedure: A two-necked flask was charged with vinyl bromide (0.5 mmol), CuI (0.05 mmol), l-proline (0.1 mmol), and Cs₂CO₃ (1.0 mmol), evacuated, and backfilled with nitrogen. The activated methylene compound (1.0 mmol) and DMSO (2 g) were added under nitrogen. The flask was immersed in a pre-heated oil bath, and the reaction mixture was stirred at 90 °C until the conversion was complete (detected by TLC). The cooled mixture was purified by column chromatography on silica gel (PE-EtOAc, 10:1 to 5:1) to provide the desired product.
( E )-3-Styrylpentane-2,4-dione (Table [2] , entry 1): IR (film): 3429.1, 3062.4, 3029.7, 2927.2, 1709.1, 1600.9, 1495.2, 1450.2, 1357.4, 1204.9, 1143.7, 1025.8, 976.2, 751.0, 699.4 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 2.21 (6 H, s, CH₃), 6.41 (1 H, d, J = 16.4 Hz, CH), 6.74 (1 H, d, J = 16.4 Hz, CH), 7.34-7.43 (5 H, m, ArH) 16.75 (1 H, s, OH). ¹³C NMR (100 MHz, CDCl₃): δ = 24.23, 111.30, 122.73, 126.05, 127.65, 128.66, 134.16, 137.02, 191.16. MS (70 eV): m/z (%) = 209.0992 (43), 176.0828 (100). HRMS (70 eV): m/z calcd for C₁₃H₁₄O₂, 202.0988; found: 202.0992.
( E )-Ethyl-2-acetyl-4-phenylbut-3-enoate (Table [2] , entry 2): IR (film): 3459.6, 3061.9, 3029.3, 2982.8, 2936.7, 1732.5, 1599.7, 1449.9, 1368.5, 1247.5, 1079.8, 1018.0, 757.9, 699.6 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.29 (1.2 H, t, J = 7.2 Hz, CH₃), 1.35 (1.8 H, t, J = 7.2 Hz, CH₃), 2.22 (1.8 H, s, CH₃), 2.28 (1.2 H, s, CH₃), 4.23 (0.8 H, q, J = 7.2 Hz, CH₂), 4.24 (0.4 H, s, CH), 4.30 (1.2 H, q, J = 7.2 Hz, CH₂), 6.42 (0.4 H, dd, J = 16.0, 9.2 Hz, CH), 6.58 (0.4 H, d, J = 16.0 Hz, CH), 6.60 (0.6 H, d, J = 16.0 Hz, CH), 6.74 (0.6 H, d, J = 16.0 Hz, CH), 7.31-7.42 (5 H, m, ArH), 13.37 (0.6 H, s, OH). ¹³C NMR (100 MHz, CDCl₃): δ = 14.03, 14.19, 20.28, 28.45, 60.92, 61.68, 63.87, 101.28, 120.99, 121.57, 125.91, 126.56, 127.04, 128.18, 128.54, 128.60, 130.62, 135.36, 135.99, 138.03, 168.41, 172.63, 174.64, 201.38. MS (70 eV): m/z (%) = 232.1099 (84) [M⁺], 205.0856 (100), 190.0986 (97), 171.0440 (62). HRMS (70 eV): m/z calcd for C₁₄H₁₆O₃: 232.1094; found: 232.1099.
( E )-Diethyl-2-styrylmalonate (Table [2] , entry 3): IR (film): 2983.3, 2938.7, 2909.6, 1732.6, 1465.2, 1449.4, 1369.3, 1258.4, 1151.3, 1033.8, 967.1, 857.8, 757.9, 692.7 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.28 (6 H, t, J = 7.2 Hz, CH₃), 4.17-4.26 (5 H, m, CH₂, CH), 6.42 (1 H, dd, J = 16.0, 8.8 Hz, CH), 6.59 (1 H, d, J = 16.0 Hz, CH), 7.27-7.42 (5 H, m, ArH). ¹³C NMR (100 MHz, CDCl₃): δ = 13.96, 55.86, 61.40, 120.84, 126.56, 128.01, 128.49, 134.96, 136.04, 167.96. MS (70 eV): m/z (%) = 262.1204 (100) [M⁺], 190.0989 (53), 189.0911 (28). HRMS (70 eV): m/z calcd for C₁₅H₁₈O₄: 262.1200; found: 262.1204.
( E )-3-(4-Chlorostyryl)pentane-2,4-dione (Table [2] , entry 5): IR (film): 3055.4, 2913.6, 1443.6, 1071.7, 748.8, 692.1 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 2.22 (6 H, s, CH₃), 6.36 (1 H, d, J = 16.4 Hz, CH), 6.72 (1 H, d, J = 16.4 Hz, CH), 7.30-7.36 (4 H, m, ArH) 16.78 (1 H, s, OH). ¹³C NMR (100 MHz, CDCl₃): δ = 24.27, 111.12, 123.38, 127.23, 128.78, 132.74, 133.22, 135.51, 191.20. MS: m/z (%) = 236.0601 (100) [M⁺], 238.0575 (35) [M⁺ + 2], 221.0365 (30). HRMS (70 eV): m/z calcd for C₁₃H₁₃ClO₂: 236.0599; found: 236.0601.
( E )-Ethyl-2-acetyl-4-(4-chlorophenyl)but-3-enoate (Table [2] , entry 6): IR (film): 3471.5, 2982.2, 2929.3, 1722.1, 1592.1, 1491.8, 1368.8, 1247.0, 1092.0, 1013.7, 974.4, 828.9 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.30 (1.2 H, t, J = 7.2 Hz, CH₃), 1.36 (1.8 H, t, J = 7.2 Hz, CH₃), 2.22 (1.8 H, s, CH₃), 2.29 (1.2 H, s, CH₃), 4.24 (0.8 H, q, J = 7.2 Hz, CH₂), 4.25 (0.4 H, s, CH), 4.30 (1.2 H, q, J = 7.2 Hz, CH₂), 6.40 (0.4 H, dd, J = 16.0, 8.8 Hz, CH), 6.52 (0.4 H, d, J = 16.0 Hz, CH), 6.56 (0.6 H, d, J = 16.0 Hz, CH), 6.71 (0.6 H, d, J = 16.0 Hz, CH), 7.27-7.34 (4 H, m, ArH), 13.41 (0.6 H, s, OH). ¹³C NMR (100 MHz, CDCl₃): δ = 14.04, 14.22, 20.32, 28.56, 61.02, 61.81, 63.72, 76.61, 101.10, 121.67, 122.15, 127.06, 127.77, 128.66, 128.79, 129.09, 132.50, 134.07, 134.48, 136.58, 168.27, 172.53, 175.02, 201.13. MS (70 eV): m/z (%) = 216.1146 (100) [M⁺], 268.0679 (38) [M⁺ + 2], 240.0554 (40), 224.0598 (80), 220.0288 (74), 207.0022 (42), 205.0052 (98). HRMS (70 eV): m/z calcd for C₁₄H₁₅ClO₃: 266.0704; found: 216.1146.
( E )-Diethyl-2-(4-chlorostyryl)malonate (Table [2] , entry 7): IR (film): 2983.7, 2934.6, 1732.7, 1492.2, 1465.7, 1446.6, 1369.5, 1256.7, 1151.2, 1094.7, 1035.1, 968.7, 821.9 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.29 (6 H, t, J = 7.2 Hz, CH₃), 4.16-4.26 (5 H, m, CH₂, CH), 6.40 (1 H, dd, J = 16.0, 8.8 Hz, CH), 6.55 (1 H, d, J = 16.0 Hz, CH), 7.28-7.35 (4 H, m, ArH). ¹³C NMR (100 MHz, CDCl₃): δ = 13.89, 55.66, 61.33, 121.49, 127.71, 128.59, 133.65, 134.50, 167.73. MS (70 eV): m/z (%) = 296.0818 (100) [M⁺], 298.0784 (32) [M⁺ + 2], 224.0600(80), 223.0522 (35), 178.0181 (40).
HRMS (70 eV): m/z calcd for C₁₅H₁₇ClO₄: 296.0810; found: 296.0818.
( E )-3-(4-Methylstyryl)pentane-2,4-dione (Table [2] , entry 8): IR (film): 3055.4, 2913.6, 1443.6, 1071.7, 748.8, 692.1 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 2.21 (6 H, s, CH₃), 2.36 (3 H, s, CH₃), 6.38 (1 H, d, J = 16.0 Hz, CH), 6.68 (1 H, d, J = 16.0 Hz, CH), 7.16 (2 H, d, J = 8.0 Hz, ArH), 7.16 (2 H, d, J = 8.0 Hz, ArH), 16.71 (1 H, s, OH). ¹³C NMR (100 MHz, CDCl₃): δ = 21.18, 24.23, 111.40, 121.72, 125.99, 129.36, 134.17, 134.24, 137.61, 191.13. MS (70 eV): m/z (%) = 216.1148 (100) [M⁺], 201.0912 (61). HRMS (70 eV): m/z calcd for C₁₄H₁₆O₃: 216.1145; found: 216.1148.
( E )-Ethyl-2-acetyl-4- p- tolylbut-3-enoate (Table [2] , entry 9): IR (film): 3459.1, 2981.7, 2923.5, 2868.0, 1721.8, 1639.5, 1604.2, 1513.6, 1369.4, 1245.6, 1061.4, 1019.3, 968.6, 860.4, 817.5 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.29 (1.2 H, t, J = 7.2 Hz, CH₃), 1.34 (1.8 H, t, J = 7.2 Hz, CH₃), 2.21 (1.8 H, s, CH₃), 2.27 (1.2 H, s, CH₃), 2.34 (3 H, s, CH₃), 4.23 (0.8 H, q, J = 7.2 Hz, CH₂), 4.24 (0.3 H, s, CH), 4.28 (1.2 H, q, J = 7.2 Hz, CH₂), 6.36 (0.4 H, dd, J = 16.0, 8.8 Hz, CH), 6.54 (0.4 H, d, J = 16.0 Hz, CH), 6.55 (0.6 H, d, J = 16.0 Hz, CH), 6.68 (0.6 H, d, J = 16.0 Hz, CH), 7.13 (2 H, d, J = 8.0 Hz, ArH), 7.29-7.31 (2 H, m, ArH), 13.34 (0.6 H, s, OH). ¹³C NMR (100 MHz, CDCl₃): δ = 14.02, 14.19, 20.23, 21.10, 21.17, 28.38, 60.85, 61.61, 63.91, 101.33, 119.90, 120.58, 125.82, 126.46, 129.22, 129.27, 130.66, 133.24, 135.22, 135.25, 136.85, 138.10, 168.51, 172.67, 174.32, 201.51. MS (70 eV): m/z (%) = 246.1254 (72) [M⁺], 204.1145 (38), 200.0832 (77), 185.0596 (100), 158.0727 (27). HRMS (70 eV): m/z calcd for C₁₅H₁₈O₃: 246.1250; found: 246.1254.
( E )-Diethyl-2-(4-methylstyryl)malonate (Table [2] , entry 10): IR (film): 2982.2, 2937.9, 1732.6, 1513.8, 1463.9, 1446.3, 1368.5, 1293.0, 1257.3, 1177.2, 1096.2, 1032.1, 968.5, 862.0, 812.0 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.28 (6 H, t, J = 7.2 Hz, CH₃), 2.33 (3 H, s, CH₃), 4.16 (1 H, d, J = 9.2 Hz, CH), 4.23 (4 H, q, J = 7.2 Hz, CH₂), 6.42 (1 H, dd, J = 16.0, 9.2 Hz, CH), 6.55 (1 H, d, J = 16.0 Hz, CH), 7.13 (2 H, d, J = 8.0 Hz, ArH), 7.31 (2 H, d, J = 8.0 Hz, ArH). ¹³C NMR (100 MHz, CDCl₃): δ = 14.01, 21.19, 55.94, 61.73, 119.79, 126.50, 129.22, 133.31, 134.89, 137.95, 168.12. MS (70 eV): m/z (%) =(100) [M⁺], 204.1147 (26), 203.1071 (28), 157.0647 (21), 129.0698 (51). HRMS (70 eV): m/z calcd for C₁₆H₂₀O₄: 276.1356; found: 276.1363.
( E )-3-(4-Methoxystyryl)pentane-2,4-dione (Table [2] , entry 11): IR (film): 3055.4, 2913.6, 1443.6, 1071.7, 748.8, 692.1 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 2.21 (6 H, s, CH₃), 2.96 (3 H, s, CH₃), 6.35 (1 H, d, J = 16.0 Hz, CH), 6.59 (1 H, d, J = 16.0 Hz, CH), 6.89-6.91 (2 H, m, ArH), 7.35-7.37 (2 H, m, ArH), 16.68 (1 H, s, OH). ¹³C NMR (100 MHz, CDCl₃): δ = 24.24, 55.34, 111.47, 114.14, 120.57, 127.29, 130.23, 133.88, 140.17, 191.10. MS (70 eV): m/z (%) = 232.1099 (100) [M⁺], 204.0782 (63), 133.0648 (37). HRMS (70 eV): m/z calcd for C₁₄H₁₆O₃: 232.1094; found: 232.1099.
( E )-3-(1-Phenylprop-1-en-2-yl)pentane-2,4-dione (Table [2] , entry 13): IR (film): 3055.4, 2913.6, 1443.6, 1071.7, 748.8, 692.1 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.99 (2 H, s, CH₃), 2.05 (3 H, d, J = 1.2 Hz, CH₃), 2.13 (4 H, s, CH₃), 6.42 (0.65 H, s, CH), 6.52 (0.35 H, s, CH), 7.18-7.40 (5 H, m, ArH), 16.40 (0.65 H, s, OH), 16.50 (0.35 H, s, OH). ¹³C NMR (100 MHz, CDCl₃): δ = 20.31, 22.84, 23.17, 27.05, 113.13, 118.18, 126.83, 126.92, 127.73, 128.25, 128.45, 128.64, 131.01, 132.60, 133.04, 133.46, 137.03, 137.34, 189.87, 190.14. MS (70 eV): m/z (%) = 216.1146 (100) [M⁺], 201.0912 (87), 173.0961 (25). HRMS (70 eV): m/z calcd for C₁₄H₁₆O₂: 216.1145; found: 216.1146.