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Synlett 2007(9): 1411-1415  
DOI: 10.1055/s-2007-980350
LETTER
© Georg Thieme Verlag Stuttgart · New York

The Synthesis of Highly Functionalized 2-(2-Methylenecycloalkyl)pyrroles by Palladium-Catalyzed Cycloreduction

Chang Ho Oh*, Wooram Park, Mira Kim
Department of Chemistry, Hanyang University, Sungdong-Gu, Seoul 133-791, South Korea
Fax: +82(2)22990762; e-Mail: changho@hanyang.ac.kr;
Further Information

Publication History

Received 15 March 2007
Publication Date:
23 May 2007 (online)

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Abstract

By utilizing the facile formation of an imine from an ­aldehyde and an amine, we have discovered a new and highly ­efficient Pd-catalyzed cycloreduction of enediynals leading to the corresponding 2-(2-methylenecycloalkyl)pyrroles in good to excellent yields.

Key words

palladium - endiynal - pyrrole - catalyst - cycloreduction

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5

General Experimental Procedure: The substrates (enediynals 1, 0.5mmol) in anhydrous dioxane (1.0 mL) were placed in a dry test tube. Then amine (1.2 equiv) was added to the reaction mixture using a microsyringe. The resultant solutions were stirred at r.t. for 30 min. To these solutions, Pd(PPh3)4 (3.0 mol%) and HCOOH (2 equiv) were added successively under an argon atmosphere. The reaction mixture was stirred for the time and temperature indicated in Table [1] . Upon completion of the reactions, as monitored by TLC, the solvent was removed under reduced pressure and the products 2 were isolated by flash column chromatography as colorless oils in the indicated yields. Full characterization using 1H NMR, 13C NMR, IR and HRMS was performed. 2aa: IR (NaCl): 1709, 1675, 1646, 1499, 1445, 1391, 1318, 1167 cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.34-7.20 (m, 3 H), 7.06 (d, J = 7.34 Hz, 2 H), 6.27 (d, J = 0.4 Hz, 1 H), 4.89 (ABq, Δδ = 10.6 Hz, J = 15.6 Hz, 2 H), 4.65 (s, 1 H), 4.24 (s, 1 H), 3.19 (t, J = 8.0 Hz, 1 H), 2.56 (m, 4 H), 2.37 (dd, J = 12.0, 2.0 Hz, 1 H), 1.98 (br t, J = 12.0 Hz, 1 H), 1.84-1.72 (m, 6 H), 1.69-1.60 (m, 2 H), 1.38-1.25 (m, 2 H); 13C NMR (100 MHz, CDCl3): δ = 149.28, 139.10, 128.46, 127.83, 127.06, 126.80, 118.69, 116.95, 115.63, 107.57, 50.52, 42.44, 36.09, 32.72, 28.20, 27.38, 24.40, 24.03, 23.51, 22.35; HRMS: m/z [M + K]+ calcd for C22H27NK: 344.1775; found: 344.1781.
2ab: IR (NaCl): 1598, 1501, 1445, 1385 cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.47-7.33 (m, 2 H), 7.34-7.23 (m, 3 H), 6.49 (s, 1 H), 4.82 (d, J = 1.6 Hz, 1 H), 4.53 (q, J = 1.6 Hz, 1 H), 3.16 (dd, J = 12.0, 3.6 Hz, 1 H), 2.75-2.56 (m, 4 H), 2.43 (d, J = 12.8 Hz, 1 H), 2.00-1.77 (m, 7 H), 1.76-1.61 (m, 2 H), 1.44-1.24 (m, 2 H); 13C NMR (100 MHz, CDCl3): δ = 149.48, 140.83, 128.75, 128.50, 126.38, 125.75, 119.89, 118.03, 116.35, 108.08, 42.48, 36.00, 32.59, 28.15, 27.13, 24.28, 24.00, 23.65, 22.23; HRMS: m/z [M + H]+ calcd for C21H26N: 292.2065; found: 292.2039.
2ac: IR (NaCl): 1707, 1647, 1445, 1376, 1316 cm-1; 1H NMR (400 MHz, CDCl3): δ = 6.34 (s, 1 H), 4.68 (s, 1 H), 4.21 (s, 1 H), 3.81-3.71 (m, 2 H), 3.30-3.21 (m, 1 H), 2.65-2.52 (m, 4 H), 2.50-2.44 (m, 1 H), 2.15-2.05 (m, 1 H), 1.99-1.84 (m, 4 H), 1.81-1.73 (m, 2 H), 1.70-1.62 (m, 2 H), 1.52-1.36 (m, 2 H), 1.29 (t, J = 7.2 Hz, 3 H); 13C NMR (100 MHz, CDCl3): δ = 149.61, 127.48, 118.52, 116.68, 114.15, 107.76, 42.53, 41.54, 36.42, 32.97, 28.49, 27.74, 24.65, 24.29, 23.67, 22.55, 17.37; HRMS: m/z [M + K]+ calcd for C17H25NK: 282.1624; found: 282.1615.
2ad: IR (NaCl): 1705, 1646, 1581, 1446, 1383, 1167 cm-1; 1H NMR (400 MHz, CDCl3): δ = 6.31 (s, 1 H), 4.69 (d, J = 2.0 Hz, 1 H), 4.22 (d, J = 2.0 Hz, 1 H), 3.67 (m, 2 H), 3.24 (dd, J = 12.0, 4.0 Hz, 1 H), 2.62-2.52 (m, 4 H), 2.47 (d, J = 13.2 Hz, 1 H), 2.09 (td, J = 13.6, 3.2 Hz, 1 H), 1.98-1.84 (m, 4 H), 1.81-1.74 (m, 2 H), 1.71-1.59 (m, 4 H), 1.52-1.39 (m, 2 H), 1.34-1.23 (m, 21 H); 13C NMR (100 MHz, CDCl3): δ = 149.20, 127.27, 118.00, 116.37, 114.81, 107.56, 46.86, 42.33, 36.20, 32.75, 31.90, 31.85, 29.64, 29.62, 29.58, 29.48, 29.33, 29.24, 28.27, 27.52, 26.89, 24.41, 24.06, 23.51, 22.68, 22.29, 14.11; HRMS: m/z [M + K]+ calcd for C27H45NK: 422.3189; found: 422.3195.
2ba: IR (NaCl): 1644, 1496, 1443, 1350, 1158 cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.32-7.21 (m, 3 H), 7.08-7.04 (m, 2 H), 6.24 (s, 1 H), 4.86 (s, 2 H), 4.67 (s, 1 H), 4.18 (s, 1 H), 3.10-3.02 (m, 1 H), 2.71-2.58 (m, 4 H), 2.42-2.35 (m, 1 H), 2.34-2.26 (m, 2 H), 2.03-1.93 (m, 2 H), 1.87-1.79 (m, 2 H), 1.78-1.69 (m, 1 H), 1.41-1.32 (m, 2 H); 13C NMR (100 MHz, CDCl3): δ = 151.58, 139.57, 129.19, 128.79, 128.75, 127.90, 127.28, 126.97, 111.58, 107.37, 50.76, 42.49, 36.30, 33.57, 31.55, 28.89, 27.22, 26.74, 25.02; HRMS (ES): m/z [M + K]+ calcd for C21H25KN: 330.1624; found: 330.1629.
2bb: IR (NaCl): 1644, 1598, 1498, 1444, 1393, 1364 cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.41-7.34 (m, 2 H), 7.31-7.27 (m, 3 H), 6.45 (s, 1 H), 4.76 (d, J = 1.6 Hz, 1 H), 4.40 (q, J = 1.6 Hz, 1 H), 3.10 (d, J = 13.2 Hz, 1 H), 2.73-2.63 (m, 4 H), 2.42-2.30 (m, 3 H), 1.95-1.87 (m, 2 H), 1.84-1.75 (m, 3 H), 1.41-1.32 (m, 2 H); 13C NMR (100 MHz, CDCl3): δ = 151.54, 141.24, 130.53, 129.36, 129.01, 126.49, 126.42, 125.94, 112.34, 108.14, 42.32, 36.29, 34.02, 31.67, 28.74, 27.16, 26.45, 24.96; HRMS: m/z [M + K]+ calcd for C20H23KN: 316.1468; found: 316.1462.
2bc: IR (NaCl): 1716, 1653, 1558, 1507, 1361 cm-1; 1H NMR (400 MHz, CDCl3): δ = 6.30 (s, 1 H), 4.65 (s, 1 H), 4.09 (s, 1 H), 3.70 (q, J = 7.2 Hz, 2 H), 3.14 (dd, J = 12.4, 2.0 Hz, 1 H), 2.56 (m, 4 H), 2.41 (br d, J = 13.2 Hz, 1 H), 2.31-2.23 (m, 2 H), 2.12-2.02 (m, 2 H), 1.94-1.85 (m, 2 H), 1.77 (ddd, J = 12.8, 12.8, 3.2 Hz, 1 H), 1.57-1.36 (m, 2 H), 1.30 (t, J = 7.2 Hz, 3 H); 13C NMR (100 MHz, CDCl3): δ = 151.57, 128.91, 127.39, 125.11, 109.72, 107.37, 42.49, 41.38, 36.39, 33.64, 31.60, 28.95, 27.39, 26.71, 25.00, 17.43; HRMS: m/z [M + K]+ calcd for C16H23KN: 230.1909; found: 230.1912.
2ca: IR (NaCl): 1670, 1644, 1600, 1520, 1494, 1447, 1390, 1349, 1332, 1169, 1119, 1075, 1030 cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.31-7.19 (m, 3 H), 7.03 (d, J = 7.6 Hz, 2 H), 6.30 (s, 1 H), 4.91 (ABq, Δδ = 23.0 Hz, J = 16.0 Hz, 2 H), 4.68 (s, 1 H), 4.44 (s, 1 H), 3.21 (dd, J = 12.0, 4.0 Hz, 1 H), 2.53 (m, 4 H), 2.40 (d, J = 13.2 Hz, 1 H), 1.96 (td, J = 12.0, 2.0 Hz, 1 H), 1.85-1.70 (m, 4 H), 1.68-1.53 (m, 5 H), 1.36-1.22 (m, 3 H); 13C NMR (100 MHz, CDCl3): δ = 149.14, 139.58, 129.44, 128.67, 127.25, 126.79, 125.34, 122.98, 117.57, 108.51, 50.90, 41.75, 36.46, 33.70, 33.60, 30.66, 30.03, 28.54, 28.24, 27.98, 27.63; HRMS: m/z [M + K]+ calcd for C23H29KN: 358.1937; found: 358.1943.
2cb: IR (NaCl): 1643, 1598, 1518, 1445, 1389, 1326, 1171, 1068 cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.39-7.33 (m, 2 H), 7.30-7.20 (m, 3 H), 6.48 (s, 1 H), 4.83 (s, 1 H), 4.70 (s, 1 H), 3.20 (dd, J = 12.0, 3.2 Hz, 1 H), 2.70-2.52 (m, 4 H), 2.45 (d, J = 14.2 Hz, 1 H), 2.01-1.56 (m, 11 H), 1.46-1.22 (m, 2 H); 13C NMR (100 MHz, CDCl3): δ = 149.84, 140.93, 129.82, 129.07, 126.70, 126.44, 125.86, 124.08, 117.97, 108.88, 42.24, 36.38, 33.66, 33.53, 30.38, 29.62, 28.45, 28.32, 28.04, 27.41; HRMS: m/z [M + K]+ calcd for C22H27KN: 344.1781; found: 344.1782.
2cc: IR (NaCl): 1700, 1645, 1520, 1446, 1389, 1321, 1170 cm-1; 1H NMR (400 MHz, CDCl3): δ = 6.31 (s, 1 H), 4.71 (d, J = 2.0 Hz, 1 H), 4.40 (q, J = 2.0 Hz, 1 H), 3.75 (m, 2 H), 3.27 (br d, J = 12.0 Hz, 1 H), 2.59-2.45 (m, 5 H), 2.15-2.05 (m, 1 H), 1.93-1.83 (m, 3 H), 1.82-1.73 (m, 3 H), 1.65-1.54 (m, 4 H), 1.48-1.37 (m, 2 H), 1.25 (t, J = 7.2 Hz, 3 H); 13C NMR (100 MHz, CDCl3): δ = 149.31, 128.79, 124.82, 122.42, 115.77, 108.44, 41.73, 41.56, 36.52, 33.65, 33.56, 30.53, 29.95, 28.49, 28.14, 28.02, 27.73, 17.32; HRMS: m/z [M + K]+ calcd for C18H27KN: 296.1781; found: 296.1777.
2da: IR (NaCl): 1730, 1496, 1445, 1388, 1366, 1298, 1262, 1247, 1186, 1155, 1056 cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.33-7.20 (m, 3 H), 7.06 (d, J = 7.2 Hz, 2 H), 6.32 (s, 1 H), 4.97 (s, 2 H), 4.94 (d, J = 2.0 Hz, 1 H), 4.65 (q, J = 2.0 Hz, 1 H), 4.16 (m, 4 H), 3.82 (br t, J = 8.8 Hz, 1 H), 3.06 (m, 2 H), 2.55 (br s, 2 H), 2.48-2.34 (m, 3 H), 2.16 (t, J = 12.8 Hz, 1 H), 1.70 (m, 4 H), 1.23 (t, J = 7.2 Hz, 3 H), 1.21 (t, J = 7.2 Hz, 3 H); 13C NMR (100 MHz, CDCl3): δ = 171.86, 171.60, 148.70, 139.08, 128.81, 127.42, 126.86, 126.28, 119.28, 117.57, 116.53, 108.22, 61.69, 58.52, 50.90, 40.55, 40.35, 39.87, 24.29, 24.20, 22.96, 22.40, 14.23, 14.21; HRMS: m/z [M + Na]+ calcd for C27H33NaNO4: 458.2307; found: 458.2314.
2db: IR (NaCl): 1731, 1598, 1500, 1386, 1348, 1187, 1071, 1022 cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.43-7.38 (m, 2 H), 7.36-7.26 (m, 3 H), 6.48 (s, 1 H), 5.00 (d, J = 2.8 Hz, 1 H), 4.75 (q, J = 2.8 Hz, 1 H), 4.18 (q, J = 7.2 Hz, 2 H), 4.14-4.04 (m, 2 H), 3.78 (m, 1 H), 3.05 (m, 2 H), 2.66-2.60 (m, 2 H), 2.59 (dd, J = 12.8, 7.6 Hz, 1 H), 2.55-2.39 (m, 2 H), 2.32 (t, J = 12.8 Hz, 1 H), 1.74 (m, 4 H), 1.24 (t, J = 7.2 Hz, 3 H), 1.13 (t, J = 7.2 Hz, 3 H); 13C NMR (100 MHz, CDCl3): δ = 171.75, 171.63, 149.21, 140.69, 129.18, 127.11, 127.03, 126.47, 120.45, 118.16, 117.20, 108.06, 61.75, 61.66, 58.58, 40.88, 40.32, 39.87, 24.20, 24.14, 23.01, 22.35, 14.26, 14.14; HRMS: m/z [M + K]+ calcd for C26H31KNO4: 460.1890; found: 460.1898.
2dc: IR (NaCl): 1730, 1446, 1377, 1298, 1186, 1071 cm-1; 1H NMR (400 MHz, CDCl3): δ = 6.33 (s, 1 H), 5.00 (d, J = 2.4 Hz, 1 H), 4.70 (d, J = 2.4 Hz, 1 H), 4.30-4.17 (m, 4 H), 3.92 (m, 1 H), 3.80 (q, J = 7.2 Hz, 2 H), 3.15 (m, 2 H), 2.67 (dd, J = 12.8, 7.6 Hz, 1 H), 2.55 (br s, 2 H), 2.47-2.32 (m, 2 H), 2.25 (t, J = 12.6 Hz, 1 H), 1.69 (m, 4 H), 1.34 (t, J = 7.2 Hz, 3 H), 1.28 (t, J = 7.2 Hz, 3 H), 1.25 (t, J = 7.2 Hz, 3 H); 13C NMR (100 MHz, CDCl3): δ = 171.84, 171.42, 148.75, 125.28, 118.69, 116.76, 114.52, 107.86, 61.55, 58.34, 41.48, 40.34, 40.10, 39.81, 24.09, 23.99, 22.65, 22.13, 21.37, 19.93, 17.18, 14.04; HRMS: m/z [M + Na]+ calcd for C22H31NaNO4: 396.2151; found: 396.2154.
2ea: IR (NaCl): 1705, 1472, 1389, 1252, 1109 cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.34-7.21 (m, 3 H), 7.10-7.05 (m, 2 H), 6.28 (s, 1 H), 4.98 (s, 2 H), 4.87 (s, 1 H), 4.62 (s, 1 H), 4.10 (m, 1 H), 3.58 (m, 1 H), 2.68 (dd, J = 16.0, 7.2 Hz, 1 H), 2.56 (m, 2 H), 2.47 (m, 2 H), 2.42-2.34 (m, 1 H), 1.94 (m, 1 H), 1.77 (dd, J = 12.4, 6.8 Hz, 1 H), 1.73-1.68 (m, 4 H), 0.85 (s, 9 H), 0.02 (s, 3 H), 0.00 (s, 3 H); 13C NMR (100 MHz, CDCl3): δ = 149.72, 139.00, 128.49, 127.16, 126.75, 118.87, 117.00, 115.88, 107.46, 71.71, 50.67, 42.50, 41.89, 39.14, 25.86, 24.12, 24.04, 22.67, 22.19, -4.71, -4.76; HRMS: m/z [M + K]+ calcd for C27H39KNOSi: 460.2438; found: 460.2434.
2eb: IR (NaCl): 1598, 1500, 1386, 1251, 1110 cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.44-7.37 (m, 2 H), 7.35-7.23 (m, 3 H), 6.45 (s, 1 H), 4.92 (d, J = 1.2 Hz, 1 H), 4.72 (q, J = 1.2 Hz, 1 H), 4.08 (m, 1 H), 3.52 (m, 1 H), 2.72-2.60 (m, 4 H), 2.54 (s, 1 H), 2.42-2.31 (m, 1 H), 2.06 (m, 1 H), 1.91 (td, J = 12.4, 9.2 Hz, 1 H), 1.82-1.69 (m, 4 H), 0.86 (s, 9 H), 0.03 (s, 3 H), 0.02 (s, 3 H); 13C NMR (100 MHz, CDCl3): δ = 150.49, 140.71, 128.94, 127.75, 126.69, 126.25, 120.17, 117.67, 116.53, 107.17, 71.57, 42.28, 41.68, 39.51, 25.86, 23.99, 23.96, 22.84, 22.16, 18.12, -4.67, -4.70; HRMS: m/z [M + K]+ calcd for C26H37NaNOSi: 430.2542; found: 430.2546.
2ec: IR (NaCl): 1710, 1658, 1471, 1376, 1252, 1109 cm-1; 1H NMR (400 MHz, CDCl3): δ = 6.33 (s, 1 H), 4.91 (s, 1 H), 4.64 (s, 1 H), 4.26 (m, 1 H), 3.81 (q, J = 7.2 Hz, 2 H), 3.67 (m, 1 H), 2.76 (dd, J = 16.0, 7.0 Hz, 1 H), 2.57 (br s, 2 H), 2.46 (br s, 2 H), 2.42 (m, 1 H), 2.21 (m, 1 H), 1.88 (td, J = 12.4, 9.0 Hz, 1 H), 1.71 (m, 4 H), 1.33 (t, J = 7.2 Hz, 3 H), 0.90 (s, 9 H), 0.08 (s, 3 H), 0.07 (s, 3 H); 13C NMR (100 MHz, CDCl3): δ = 150.48, 126.47, 118.77, 116.80, 114.32, 107.45, 72.06, 42.73, 42.12, 41.57, 39.31, 26.12, 24.41, 24.32, 22.76, 22.41, 18.43, 17.24, -4.42, -4.46; HRMS: m/z [M + H]+ calcd for C22H38NOSi: 360.2723; found: 360.2724.
2fa: IR (NaCl): 1705, 1597, 1495, 1453, 1387, 1346, 1163, 1094, 1041, 1008 cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.63 (d, J = 8.8 Hz, 2 H), 7.32-7.24 (m, 5 H), 6.95-6.92 (m, 2 H), 6.32 (s, 1 H), 4.90 (d, J = 2.4 Hz, 1 H), 4.86 (s, 2 H), 4.61 (q, J = 2.4 Hz, 1 H), 4.05 (br d, J = 14.0 Hz, 1 H), 3.82 (m, 1 H), 3.78-3.70 (m, 1 H), 3.49 (t, J = 9.0 Hz, 1 H), 2.95 (t, J = 9.0 Hz, 1 H), 2.51 (t, J = 6.0 Hz, 2 H), 2.42 (s, 3 H), 2.22-2.12 (m, 1 H), 1.95 (dt, J = 15.6, 6.4 Hz, 1 H), 1.71-1.61 (m, 2 H), 1.61-1.54 (m, 2 H); 13C NMR (100 MHz, CDCl3): δ = 144.73, 143.62, 138.44, 132.34, 129.60, 128.65, 127.78, 127.43, 126.22, 122.58, 119.19, 118.20, 117.26, 108.08, 52.34, 52.14, 50.70, 40.22, 23.86, 23.78, 22.63, 21.96, 21.53; HRMS (ES+): m/z [M + K]+ calcd for C27H30KN2: 421.2046; found: 421.2050.