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.

Key words

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

References and Notes

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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.