Domino reactions of 2-methyl chromones containing an electron withdrawing group with chromone-fused dienes

Domino reactions of 2-methyl chromones containing an electron withdrawing group with chromone-fused dienes Jian Gong, Fuchun Xie, Wenming Ren, Hong Chen and Youhong Hu* State Key Laboratory of Drug Research, Shanghi Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai, 201203, China yhhu@mail.shcnc.ac.cn Supporting Information List of contents Experiment procedures..s2 Characterization data: 3 and 4,...S3-S11 1 H NMR, 13 C NMR and IR spectra...s12-s65 X-ray crystal structure of 3e..S66 S1

1. Experiment procedures All reactions were performed under air atmosphere. Solvents were used without purification. Petroleum ether refers to the fraction with boiling point in the range 60 90 C. All 1 H NMR and 13 C NMR spectra were measured in CDCl3 or DMSO-d 6 with TMS as the internal standard. Chemical shifts are expressed in ppm and J values are given in Hz. High resolution mass spectra were recorded on a Finnigan MAT 95 mass spectrometer (EI) or IonSpec 4.7 Tesla FTMS (ESI). Column chromatography was performed with 300-400 mesh silica gel using flash column techniques. Melting points are uncorrected. All microwave irradiation reactions were conducted by using CEM microwave reactor. Compounds 2 were prepared according to the reported method. 1, 2 General Procedure: A typical procedure for the preparation of 3a: To the solution of 1a (52 mg, 0.2 mmol) and 2a (49 mg, 0.2 mmol) in THF (1.5 ml) in a 10 ml microwave vial containing a magnetic stir bar was added DBU (60 µl, 0.4 mmol). The reaction vessel was sealed and heated in a microwave reactor at 100 ºC for 10 min. After cooling, the resulting mixture was diluted with water (20 ml) and extracted with ethyl acetate (15 ml 3) and the combined organic layers were washed with brine (10 ml), dried over anhydrous Na 2 SO 4, filtered and concentrated to give the crude product, which was further purified by column chromatography (petroleum ether/ethyl acetate 10:1 to petroleum ether/ethyl acetate 4:1) to afford compound 3a as a light yellow solid. A typical procedure for the preparation of 4a: To the solution of 1a (52 mg, 0.2 mmol) and 2j (49 mg, 0.2 mmol) in THF (1.5 ml) in a 10 ml round-bottom flask containing a magnetic stir bar was added base (0.4 mmol). The reaction vessel was heated in oil bath at 100 ºC for 2h. After cooling, the resulting mixture was diluted with water (20 ml) and extracted with ethyl acetate (15 ml 3) and the combined organic layers were washed with brine (10 ml), dried over anhydrous Na 2 SO 4, filtered and concentrated to give the crude product, which was further purified by column chromatography (petroleum ether/ethyl acetate 10:1 to petroleum ether/ethyl acetate 4:1) to afford compound 3a as a light yellow solid. S2

2. Characterization Data: As a yellow solid: m.p. 208-209 o C; IR (KBr) ν max 2922, 2852, 1641, 1626, 1614, 1585, 1485, 1469, 1415, 1304, 1223, 1151, 931, 756, 712 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ): δ 12.00 (s, 1H), 10.34 (d, J = 9.0 Hz, 1H), 8.47 (d, J = 7.9 Hz, 1H), 8.28 (s, 1H), 8.05 (d, J =8.9 Hz, 1H), 7.77 (t, J = 3.6 Hz, 1H), 7.64-7.43 (m, 10H), 7.06 (d, J = 8.1 Hz, 1H), 6.87 ppm (t, J = 7.6 Hz, 1H); 13 C NMR (100 MHz, CDCl 3 ): δ 201.0, 177.9, 163.2, 157.9, 154.7, 149.6, 138.1, 136.4, 135.0, 134.3, 134.0, 133.5, 129.6, 128.82, 128.78, 128.71, 128.4, 128.2, 127.2, 126.7, 124.7, 123.6, 119.9, 119.1, 118.6, 118.4, 117.6, 113.6 ppm; HRMS calcd for C 30 H 19 O 4 : 443.1262, found: 443.1278. As a white solid: m.p. 225-226 o C; IR (KBr) ν max 3425, 3070, 1643, 1620, 1603, 1589, 1504, 1469, 1421, 1327, 1306, 1217, 876, 762 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ): δ 12.08 (s, 1H), 10.29 (d, J = 9.0 Hz 1H), 8.49-8.38 (m, 2H), 8.04 (dd, J =8.9,1.8 Hz, 1H), 7.76 (dt, J = 7.2,1.6 Hz, 1H), 7.68 (dd, J = 8.0, 1.6 Hz, 1H), 7.62-7.52 (m, 3H), 7.48 (dt, J = 8.0, 0.9 Hz, 1H), 7.13 (dd, J = 8.4, 0.9 Hz 1H), 6.92 (dt, J = 8.0, 1.0 Hz, 1H), 2.85 ppm (d, J = 0.8, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ 201.3, 178.0, 163.3, 158.4, 154.6, 145.2, 136.5, 135.0, 134.1, 133.7, 133.6, 129.1, 128.8, 127.4, 126.7, 125.8, 124.6, 123.6, 119.7, 119.3, 118.8, 118.5, 117.6, 113.2, 20.4 ppm; HRMS calcd for C 25 H 17 O 4 (M+H) + : 381.1114, found: 381.1121. S3

As a yellow solid: m.p. 210-211 o C; IR (KBr) ν max 3431, 2962, 1649, 1608, 1514, 1468, 1442, 1398, 1306, 1255, 1153, 1032, 931, 758 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ): δ 12.04 (s, 1H), 10.34 (d, J = 8.9 Hz, 1H), 8.47 (d, J = 8.2 Hz, 1H), 8.34 (s, 1H), 8.04 (d, J = 8.9 Hz, 1H), 7.77 (t, J = 7.7 Hz, 1H), 7.66-7.45 (m, 7H), 7.14-7.00 (m, 3H), 6.88 (t, J = 7.6 Hz, 1H), 3.90 ppm (s, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ 201.1, 178.0, 163.3, 160.1, 158.0, 154.7, 149.5, 136.4, 135.0, 134.2, 134.1, 133.6, 130.9, 130.4, 128.8, 128.5, 127.2, 126.8, 124.7, 123.7, 119.7, 119.2, 118.7, 118.5, 117.6, 114.2, 113.4, 55.4 ppm; HRMS calcd for C 31 H 21 O 5 (M+H) + : 473.1375, found: 473.1384. As a yellow solid: m.p. 215-216 o C; IR (KBr) ν max 2956, 2924, 2854, 1647, 1610, 1581, 1527, 1466, 1444, 1373, 1304, 1219, 1151, 822, 758 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ): δ 12.07 (s, 1H), 10.34 (d, J = 8.9 Hz 1H), 8.48 (m, 2H), 8.04 (dd, J = 8.9, 1.7 Hz, 1H), 7.77 (t, J = 7.2 Hz, 1H), 7.66 (dd, J = 8.1, 1.5 Hz, 1H), 7.62-7.43 (m, 6H), 7.08 (d, J = 8.0 Hz, 1H), 6.94-6.80 (m, 3H), 3.05 ppm (s, 6H); 13 C NMR (100 MHz, CDCl 3 ): δ 201.3, 178.0, 163.2, 158.3, 154.8, 150.7, 136.3, 134.9, 134.3, 134.1, 133.7, 130.7, 128.8, 128.7, 128.6, 127.1, 126.8, 125.7, 124.5, 123.8, 119.3, 119.1, 118.7, 118.4, 117.5, 113.0, 112.2, 40.3 ppm; HRMS calcd for C 32 H 24 NO 4 (M+H) + : 486.1687, found: 486.1699. S4

As a white solid: m.p. 200-201 o C; IR (KBr) ν max 2962, 1645, 1612, 1587, 1466, 1442, 1415, 1302, 1223, 1153, 1107, 1034, 930, 816, 758 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ): δ 12.03 (s, 1H), 10.34 (d, J = 8.9 Hz, 1H), 8.47 (d, J = 8.1 Hz, 1H), 8.32 (s, 1H), 8.04 (d, J = 8.8, 0.8 Hz, 1H), 7.78 (t, J = 4.1 Hz, 1 H), 7.66-7.40 (m, 7H), 7.38-7.29 (m, 2H), 7.06 (d, J = 8.7 Hz, 1H), 6.88(t, J = 7.5Hz, 2H), 2.45 ppm (s, 3H) ; 13 C NMR (100 MHz, CDCl 3 ): δ 201.1, 178.0, 163.3, 158.0, 154.7, 149.8, 138.8, 136.4, 135.3, 135.0, 134.2, 134.0, 133.6, 129.5, 129.4, 128.8, 128.5, 128.3, 127.2, 126.8, 124.7, 123.7, 119.8, 119.2, 118.7, 118.4, 117.6, 113.5, 21.3 ppm; HRMS calcd for C 31 H 21 O 4 (M+H) + : 457.1430, found: 457.1434. As a yellow solid: m.p. 220-221 o C; IR (KBr) ν max 3066, 1693, 1639, 1614, 1468, 1325, 1157, 1117, 1066, 847, 760 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ): δ 11.96 (s, 1H), 10.37 (d, J = 9.0 Hz, 1H), 8.49 (dd, J = 8.0, 1.6 Hz, 1H), 8.17 (d, J = 2.0 Hz, 1H), 8.07 (dd, J = 8.6, 1.7 Hz, 1H), 7.85-7.76 (m, 3H), 7.71-7.47 (m, 7H), 7.07 (d, J = 7.9 Hz, 1H), 6.87 ppm (t, J = 7.5 Hz, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 200.9, 178.0, 163.3, 154.7, 141.8, 136.6, 135.4, 134.5, 134.1, 133.9, 133.4, 130.0, 129.1, 127.9, 127.7, 127.3, 126.8, 125.8, 125.8, 124.9, 123.6, 120.2, 119.0, 118.7, 118.6, 118.6, 117.7, 117.6, 114.1 ppm; HRMS calcd for C 31 H 18 F 3 O 4 (M+H) + : 511.1134, found: 511.1152. S5

As a yellow solid: m.p. 230-231 o C; IR (KBr) ν max 3440, 2924, 1693, 1641, 1614, 1587, 1560, 1466, 1388, 1304, 1221, 1151, 841, 758 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ): δ 12.00 (s, 1H), 10.35 (d, J = 8.6 Hz, 1H), 8.48 (dd, J = 8.0, 1.6 Hz, 1H), 8.23 (d, J = 1.8 Hz, 1H), 8.06 (dd, J = 9.1, 1.8 Hz, 1H), 7.79 (dt, J = 7.8, 1.7 Hz, 1H), 7.66-7.40 (m, 7H), 7.29-7.17 (m, 2H), 7.07 (d, J = 8.5 Hz, 1H), 6.87 ppm (t, J = 7.2 Hz, 1H); 13 C NMR (100 MHz, CDCl 3 ): δ 200.8, 177.8, 163.8, 163.3, 162.2, 157.7, 154.6, 148.4, 136.5, 135.1, 134.3, 134.1, 133.9, 133.4, 131.34, 131.28, 128.9, 128.2, 128.1, 127.2, 126.7, 124.7, 123.6, 120.0, 119.1, 118.6, 118.5, 117.5, 115.9, 115.8, 113.7 ppm; HRMS calcd for C 30 H 18 FO 4 (M+H) + : 461.1169, found: 461.1184. As a yellow solid: m.p. 200-201 o C; IR (KBr) ν max 3429, 3062, 1720, 1647, 1612, 1485, 1466, 1304, 1219, 1153, 1009, 930, 829, 756 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ): δ 11.99 (s, 1H), 10.33 (d, J = 8.8 Hz, 1H), 8.46 (dd, J = 8.1, 1.3 Hz, 1H), 8.22 (d, J = 1.9 Hz, 1H), 8.04 (dd, J = 8.6, 1.8 Hz, 1H), 7.78 (t, J = 7.8 Hz, 1H), 7.68 (d, J = 8.0 Hz, 2H), 7.60-7.40 (m, 7H), 7.08 (d, J = 8.2 Hz, 1H), 6.88 ppm (t, J = 7.5 Hz, 1H); 13 C NMR (100 MHz, CDCl 3 ): δ 200.9, 177.9, 163.3, 157.8, 154.7, 148.2, 137.1, 136.6, 135.3, 134.4, 134.0, 133.5, 132.0, 131.2, 129.0, 128.0, 127.9, 127.3, 126.8, 124.8, 123.7, 123.3, 120.0, 119.1, 118.7, 118.6, 117.6, 113.9 ppm; HRMS calcd for C 30 H 18 BrO 4 (M+H) + : 521.0373, found: 521.0383. S6

As a yellow solid: m.p. 275-276 o C; IR (KBr) ν max 3109, 1649, 1624, 1610, 1589, 1514, 1466, 1417, 1348, 1306, 1155, 931, 854, 766 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 11.93 (s, 1H), 10.37 (d, J = 8.8 Hz, 1H), 8.48 (d, J = 8.0 Hz, 1H), 8.42 (d, J = 8.3 Hz, 2H), 8.08 (dd, J = 10.9, 1.8 Hz, 2H), 7.85 7.67 (m, 3H), 7.66 (s, 1H), 7.55 (dt, J = 15.2, 8.2 Hz, 4H), 7.08 (d, J = 8.4 Hz, 1H), 6.88 (t, J = 7.6 Hz, 1H). 13 C NMR (100 MHz, CDCl 3 ) δ 200.7, 177.9, 163.3, 157.5, 154.7, 148.0, 146.7, 144.7, 136.7, 135.6, 133.9, 134.6, 133.3, 130.6, 129.3, 127.6, 127.4, 127.4, 126.8, 125.0, 124.0, 123.6, 120.3, 119.0, 118.7, 118.6, 117.6, 114.4 ppm. HRMS calcd for C 30 H 17 NO 6 M + : 487.1056, found: 487.1049. As a yellow solid: m.p. 210-211 o C. IR (KBr) ν max 3423, 3053, 2924, 1641, 1626, 1612, 1583, 1485, 1469, 1415, 1329, 1304, 1223, 1159, 916, 758, 706 cm -1 ; 1 H NMR (500 MHz, CDCl 3 ) δ 12.01 (s, 1H), 10.36 (d, J = 8.9 Hz, 0.48H), 8.49 (dd, J = 8.0, 1.5 Hz, 1H), 8.29 (d, J = 1.8 Hz, 1H), 8.06 (td, J = 4.5, 1.9 Hz, 1H), 7.78 (ddd, J = 8.6, 7.2, 1.6 Hz, 1H), 7.65 (s, 0.38H), 7.62 (dd, J = 8.0, 1.5 Hz, 1H), 7.61 7.46 (m, 8H), 7.10 7.04 (m, 1H), 6.92 6.84 ppm (m, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ = 201.0, 178.0, 163.2, 157.9, 154.7, 149.6, 138.1, 136.4, 135.0, 134.3, 133.5, 129.6, 128.9, 128.8, 128.2, 128.8, 128.7, 127.2, 126.8, 124.7, 123.6, 119.9, 119.1, 118.7, 118.7, 118.4, 117.6, 113.7 ppm. HRMS calcd for C 30 H 16 D 2 O 4 (M+Na) + : 467.1331, found: 467.1238. S7

As a yellow solid: m.p. 75-76 o C; IR (KBr) ν max 2979, 1724, 1641, 1626, 1603, 1577, 1466, 1398, 1363, 1294, 1230, 1169, 1084, 1020, 972, 760 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 11.89 (s, 1H), 8.39 (d, J = 1.8 Hz, 1H), 8.22 (dd, J = 8.0, 1.3 Hz, 1H), 7.88 (dd, J = 7.9, 1.9 Hz, 1H), 7.68 (m, 2H), 7.60 7.51 (dt, J = 8.0, 1.5 Hz, 1H), 7.48 (d, J = 8.5 Hz, 1H), 7.40 (m, 2H), 7.10 (d, J = 8.4 Hz, 1H), 6.97 6.87 (dt, J = 7.6, 1.1 Hz, 1H), 4.19 (q, J = 7.1 Hz, 2H), 2.28 (s, 3H), 1.14 (t, J = 7.1 Hz, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ 200.3, 176.3, 165.7, 163.3, 161.9, 156.0, 138.0, 137.7, 136.8, 133.6, 133.5, 132.3, 132.2, 131.8, 131.3, 126.2, 124.9, 123.2, 122.9, 119.0, 118.8, 118.5, 117.7, 61.3, 19.5, 13.7 ppm. HRMS calcd for C 26 H 20 O 6 M + : 428.1260, found: 428.1268. As a yellow solid: m.p. 230-231 o C; IR (KBr) ν max 3404, 3060, 2227, 1649, 1633, 1599, 1481, 1462, 1398, 1367, 1302, 1225, 978, 760 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 11.76 (s, 1H), 8.25 (d, J = 8.0 Hz, 1H), 8.09 (s, 1H), 7.98 (d, J = 8.5 Hz, 1H), 7.73 (d, J = 8.4 Hz, 1H), 7.65 7.41 (m, 5H), 7.12 (d, J = 8.4 Hz, 1H), 6.96 (t, J = 7.6 Hz, 1H), 2.39 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 198.7, 175.6, 164.6, 163.3, 155.9, 140.6, 138.0, 137.2, 134.1, 133.4, 133.0, 132.3, 126.2, 125.5, 122.9, 120.0, 119.2, 118.7, 118.4, 117.8, 116.8, 114.7, 19.6 ppm. HRMS calcd for C 24 H 15 NO 4 M + : 381.1101, found: 381.1005. As a yellow solid: m.p. 130-131 o C; IR (KBr) ν max 2914, 1641, 1628, 1614, 1579, 1487, 1446, 1338, 1265, 1238, 1211, 1146, 953, 752 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 12.03 (s, 1H), 8.25 (dd, J = 8.0, 1.4 Hz, 1H), 7.81 7.70 (m, 3H), 7.65 (ddd, J = 8.8, 7.2, 1.7 Hz, 1H), 7.56 7.49 (m, 1H), 7.47 7.43 (m, 1H), 7.42 7.34 (m, 2H), 7.34 7.27 (m, 3H), 7.25 7.21 (m, 2H), 7.08 (d, J = 8.4 Hz, 1H), 6.95 6.86 (m, 1H), 1.93 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ 201. 2, 177.2, 163.4, 163.2, 155.8, 142.9, 140.1, 137.9, S8

136.5, 135.7, 133.8, 133.5, 131.8, 130.8, 128.9, 128.3, 128.1, 127.4, 126.2, 125.0, 122.9, 122.6, 119.0, 118.8, 118.3, 117.7, 19.3 ppm. HRMS calcd for C 29 H 20 O 4 M + : 432.1362, found: 432.1358. As a yellow solid: m.p. 180-181 o C; IR (KBr) ν max 2837, 1633, 1622, 1608, 1595, 1574, 1516, 1462, 1394, 1361, 1282, 1228, 1196, 1109, 1030, 955, 835, 764 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 12.04 (s, 1H), 8.30 8.19 (m, 1H), 7.76 (dd, J = 9.4, 1.4 Hz, 2H), 7.70 (dd, J = 7.8, 1.7 Hz, 1H), 7.67 7.60 (m, 1H), 7.52 (t, J = 7.8 Hz, 1H), 7.43 (d, J = 7.8 Hz, 2H), 7.40 7.34 (m, 1H), 7.25 7.18 (m, 2H), 7.08 (d, J = 8.4 Hz, 1H), 6.90 (t, J = 7.6 Hz, 1H), 6.79 (t, J = 5.8 Hz, 2H), 3.75 (s, 3H), 1.93 (s, 3H). 13 C NMR (101 MHz, cdcl 3 ) δ 201.3, 177.2, 163.4, 163.2, 158.9, 155.9, 142.6, 137.9, 136.4, 135.7, 133.8, 133.5, 132.5, 131.7, 130.7, 129.7, 127.8, 126.2, 124.9, 122.9, 122.7, 119.1, 118.8, 118.3, 117.7, 113.7, 55.1, 19.3 ppm. HRMS calcd for C 29 H 20 O 4 M + : 462.1467, found: 462.1483. As a yellow solid: m.p. 215-216 o C; IR (KBr) ν max 3423, 3074, 1732, 1633, 1604, 1576, 1514, 1464, 1402, 1348, 1234, 1109, 949, 860, 758, 708 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 11.94 (s, 1H), 8.19 (d, J = 7.9 Hz, 1H), 8.12 (d, J = 8.5 Hz, 2H), 7.86 7.76 (m, 2H), 7.72 (d, J = 8.2 Hz, 1H), 7.66 (d, J = 8.1 Hz, 1H), 7.55 (d, J = 7.2 Hz, 1H), 7.49 (dd, J = 8.3, 4.1 Hz, 3H), 7.41 (t, J = 8.6 Hz, 2H), 7.10 (d, J = 8.4 Hz, 1H), 6.92 (t, J = 7.6 Hz, 1H), 2.03 (s, 3H).. 13 C NMR (101 MHz, cdcl 3 ) δ 200.6, 176.8, 163.5, 163.3, 155.8, 147.2, 146.9, 140.9, 138.3, 136.8, 135.7, 133.9, 133.5, 132.0, 130.4, 129.5, 129.4, 126.1, 125.3, 123.6, 122.7, 122.1, 118.9, 118.5, 117.8, 19.4 ppm. HRMS calcd for C 29 H 20 O 4 M + : 477.1212, found: 477.1230. S9

As a yellow solid: m.p. 260-261 o C; IR (KBr) ν max 3047, 1676, 1633, 1604, 1574, 1529, 1462, 1375, 1352, 1302, 1242, 1155, 928, 768 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 11.83 (s, 1H), 10.30 (d, J = 9.0 Hz, 1H), 8.50 8.40 (m, 3H), 8.27 (dd, J = 22.3, 9.7 Hz, 2H), 8.02 (d, J = 8.6 Hz, 2H), 7.85 (t, J = 7.8 Hz, 1H), 7.73 (d, J = 8.2 Hz, 1H), 7.56 (t, J = 6.7 Hz, 3H), 7.11 (d, J = 8.8 Hz, 1H), 6.91 (t, J = 7.6 Hz, 1H). 13 C NMR (100 MHz, CDCl 3 ) δ 199.7, 194.0, 175.2, 163.3, 156.3, 153.6, 150.1, 141.6, 138.8, 137.4, 137.3, 137.0, 134.8, 134.2, 133.0, 132.0, 131.4, 130.9, 129.3, 126.3, 125.6, 124.4, 123.7, 123.5, 118.9, 118.7, 118.2 ppm. HRMS calcd for C 29 H 17 NO 7 M + : 491.1005, found: 491.1000. As a yellow solid: m.p. 255-256 o C; IR (KBr) ν max 3257, 3084, 1718, 1678, 1624, 1608, 1545, 1572, 1522, 1485, 1385, 1352, 1240, 1215, 1165, 1080, 982, 850, 758 cm -1 ; 1 H NMR (500 MHz, Acetone) δ 11.63 (s, 1H), 8.92 (d, J = 8.3 Hz, 1H), 8.34 (d, J = 8.9 Hz, 2H), 8.07 (d, J = 8.9 Hz, 2H), 8.01 (dd, J = 7.9, 1.1 Hz, 1H), 7.92 (dd, J = 8.3, 1.7 Hz, 1H), 7.79 7.72 (m, 1H), 7.60 7.54 (m, 1H), 7.51 (dd, J = 8.0, 1.3 Hz, 1H), 7.48 7.39 (m, 3H), 7.15 (br, 1H),7.02 (d, J = 8.3 Hz, 1H), 6.89 (t, J = 7.6 Hz, 1H). 13 C NMR (126 MHz, Acetone) δ 199.5, 199.4, 162.5, 162.2, 159.1, 153.3, 148.5, 147.5, 136.8, 136.3, 136.3, 133.4, 132.9, 132.2, 130.3, 128.5, 127.4, 125.0, 124.4, 123.6, 123.3, 119.3, 118.8, 117.9, 117.8, 116.3, 115.3, 100.5 ppm. HRMS calcd for C 29 H 17 NO 8 M + : 507.0954, found: 507.0962. S10

As a yellow solid: m.p. 260-261 o C; IR (KBr) ν max 3429, 3113, 2920, 1736, 1651, 1614, 1545, 1466, 1425, 1352, 1304, 1223, 1153, 766 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 11.83 (s, 1H), 10.30 (d, J = 9.0 Hz, 1H), 8.54 8.39 (m, 3H), 8.27 (dd, J = 22.3, 9.7 Hz, 2H), 8.02 (d, J = 8.6 Hz, 2H), 7.85 (t, J = 7.8 Hz, 1H), 7.73 (d, J = 8.2 Hz, 1H), 7.56 (t, J = 6.7 Hz, 3H), 7.11 (d, J = 8.8 Hz, 1H), 6.91 (t, J = 7.6 Hz, 1H). 13 C NMR (100 MHz, pyridine) δ 199.8, 178.9, 165.3, 163.4, 154.4, 143.1, 138.4, 137.1, 136.5, 135.3, 133.2, 133.0, 131.2, 129.6, 129.2, 127.1, 126.7, 126.3, 126.2, 125.4, 124.7, 124.0, 123.8, 123.2, 119.0, 118.9, 118.7, 118.2, 107.4 ppm. HRMS calcd for C 29 H 16 N 2 O 6 M + : 488.1008, found: 488.1013 references (1) Anh-Thu Dang, David O. Miller, Louise N. Dawe, and Graham J. Bodwell, Org.Lett. 2008, 10, 233. (2) V. A. Tuskaev, É. T. Oganesyan, and S. Kh. Mutsueva, Pharm. Chem. J. 2002, 36, 309. S11

12.000 10.353 10.323 8.483 8.456 8.279 8.065 8.035 7.763 7.739 7.622 7.603 7.582 7.552 7.535 7.506 7.480 7.456 7.260 7.076 7.049 6.893 6.868 6.843 1.618 0.003 Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry 3. IR, 1 H NMR and 13 C NMR spectra 10.25 0.87 1.02 1.06 1.09 1.03 1.09 1.00 1.00 12 10 8 6 4 2 0-2 PPM S12

S13

S14

10.297 10.275 12.091 8.460 8.456 8.440 8.436 8.426 8.422 8.054 8.049 8.032 8.027 7.785 7.781 7.767 7.763 7.759 7.746 7.742 7.691 7.687 7.671 7.667 7.581 7.574 7.560 7.556 7.553 7.539 7.530 7.528 7.495 7.492 7.475 7.457 7.455 7.259 7.141 7.139 7.120 7.118 6.943 6.939 6.922 6.904 6.902 2.846 2.844 1.587-0.006 Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry 1.04 0.99 1.91 2.91 1.00 1.00 1.00 0.99 0.91 0.98 3.12 12 10 8 6 4 2 PPM S15

S16

S17

12.035 10.352 10.323 8.481 8.454 8.338 8.057 8.027 7.793 7.769 7.742 7.643 7.616 7.603 7.589 7.561 7.538 7.508 7.499 7.485 7.471 7.259 7.085 7.074 7.059 7.045 6.908 6.883 6.858 3.897 3.878 0.005 Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry 7.04 0.81 0.90 1.00 0.92 1.02 1.02 3.03 1.05 3.03 12 10 8 6 4 2 PPM S18

S19

S20

12.070 10.360 10.330 8.484 8.477 8.468 8.463 8.057 8.051 8.027 8.021 7.791 7.767 7.743 7.739 7.683 7.677 7.656 7.651 7.606 7.597 7.568 7.536 7.510 7.478 7.456 7.448 7.262 7.088 7.062 6.922 6.898 6.872 6.863 6.834 3.088 3.054 1.571 0.011 0.000 Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry 6.18 6.04 0.81 0.92 1.97 1.00 1.07 1.09 1.04 3.12 12 10 8 6 4 2 0 PPM S21

S22

S23

12.027 10.354 10.324 8.486 8.459 8.321 8.057 8.055 8.029 8.026 7.766 7.741 7.739 7.639 7.610 7.587 7.559 7.535 7.507 7.483 7.454 7.427 7.350 7.324 7.259 7.258 7.083 7.054 6.902 6.877 6.853 2.454 1.599 0.002-0.001 Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry 6.93 0.83 0.98 1.01 1.09 0.92 1.00 1.97 0.99 0.93 3.20 12 10 8 6 4 2 PPM S24

S25

S26

10.380 11.963 10.350 8.502 8.497 8.476 8.470 8.174 8.168 8.083 8.077 8.054 8.048 7.827 7.799 7.775 7.769 7.697 7.669 7.643 7.613 7.599 7.593 7.586 7.573 7.567 7.547 7.540 7.537 7.513 7.495 7.490 7.486 7.255 7.086 7.060 6.894 6.871 6.844 1.577-0.003 Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry 7.35 3.08 0.91 1.00 1.01 1.06 0.99 0.98 0.99 12 10 8 6 4 2 PPM S27

S28

S29

11.997 10.365 10.336 8.496 8.491 8.469 8.464 8.236 8.230 8.078 8.072 8.048 8.042 7.786 7.782 7.622 7.612 7.601 7.591 7.586 7.574 7.551 7.547 7.533 7.528 7.522 7.513 7.505 7.501 7.265 7.255 7.237 7.209 7.089 7.064 7.060 6.873 1.572-0.002 Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry 7.07 0.91 1.00 0.83 0.89 1.05 1.02 1.36 0.93 0.58 0.90 12 10 8 6 4 2 0 PPM S30

S31

S32

11.994 10.346 10.316 8.477 8.473 8.450 8.446 8.215 8.209 8.058 8.051 8.029 8.023 7.798 7.775 7.752 7.746 7.686 7.660 7.597 7.586 7.579 7.575 7.560 7.549 7.517 7.490 7.465 7.435 7.408 7.255 7.090 7.063 6.900 6.875 6.851-0.002 Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry 7.08 0.77 0.96 1.00 0.98 0.89 2.07 1.02 1.12 0.96 12 10 8 6 4 2 PPM S33

S34

S35

11.930 10.387 10.358 8.497 8.470 8.433 8.405 8.105 8.098 8.067 8.062 7.831 7.807 7.779 7.765 7.737 7.703 7.679 7.662 7.615 7.586 7.558 7.544 7.520 7.493 7.258 7.089 7.062 6.901 6.874 6.851 1.574-0.005 Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry 4.05 3.05 1.78 1.86 0.70 0.95 1.13 0.82 0.85 0.89 12 10 8 6 4 2 PPM S36

S37

S38

S39

S40

S41

11.933 8.393 8.386 8.233 8.229 8.207 8.202 7.897 7.891 7.871 7.865 7.688 7.683 7.678 7.660 7.654 7.651 7.548 7.545 7.519 7.490 7.461 7.429 7.403 7.376 7.259 7.112 7.087 7.085 6.950 6.946 6.922 6.919 6.896 4.227 4.204 4.180 4.156 2.281 1.635 1.163 1.140 1.116-0.005 Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry 1.84 1.86 1.93 2.77 2.82 0.80 0.83 0.88 0.93 1.01 0.92 0.92 1.00 12 10 8 6 4 2 PPM S42

S43

S44

11.759 8.267 8.240 8.091 7.996 7.993 7.970 7.968 7.964 7.738 7.711 7.620 7.591 7.557 7.531 7.502 7.488 7.461 7.437 7.262 7.135 7.108 6.983 6.958 6.933 4.488 2.392 1.584-0.001 Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry 5.15 2.83 0.95 0.91 0.98 0.94 1.06 1.00 1.01 10 8 6 4 2 0-2 PPM S45

S46

S47

12.033 8.267 8.262 8.240 8.235 7.779 7.773 7.754 7.752 7.728 7.722 7.675 7.656 7.652 7.627 7.623 7.547 7.524 7.500 7.494 7.465 7.440 7.431 7.406 7.404 7.383 7.355 7.325 7.321 7.316 7.309 7.297 7.291 7.283 7.269 7.266 7.258 7.251 7.239 7.233 7.098 7.070 6.931 6.928 6.904 6.880 6.878 1.931 Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry 2.87 3.22 0.76 0.88 1.92 1.13 1.18 1.94 1.16 1.00 1.22 2.89 12 10 8 6 4 2 PPM S48

S49

S50

12.040 8.272 8.267 8.247 8.245 8.241 7.782 7.777 7.749 7.746 7.716 7.710 7.690 7.686 7.658 7.633 7.629 7.519 7.440 7.412 7.396 7.384 7.368 7.258 7.238 7.215 7.208 7.095 7.067 6.924 6.900 6.874 6.794 6.772 6.765 3.745 1.927 1.631 1.625-0.004 Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry 2.29 2.07 1.99 2.06 3.30 3.19 0.87 1.06 1.32 1.17 1.23 0.86 1.00 1.09 12 10 8 6 4 2 0 PPM S51

S52

S53

11.936 8.206 8.178 8.131 8.103 7.817 7.812 7.786 7.769 7.732 7.705 7.674 7.652 7.647 7.565 7.541 7.506 7.491 7.477 7.464 7.439 7.411 7.382 7.259 7.108 7.081 6.942 6.917 6.891 2.032 1.630 1.625-0.010 Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry 3.11 3.23 0.79 1.97 0.94 1.98 2.20 1.23 0.96 0.87 1.00 1.08 12 10 8 6 4 2 PPM S54

S55

S56

11.801 8.318 8.289 8.204 8.118 8.090 8.066 7.958 7.953 7.931 7.928 7.722 7.693 7.667 7.613 7.589 7.563 7.534 7.518 7.490 7.398 7.373 7.349 7.260 7.096 7.069 6.924 6.923 6.899 6.874 1.573-0.002 Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry 1.16 2.68 2.28 1.89 1.96 1.88 1.07 1.08 1.00 1.04 1.06 12 10 8 6 4 2 0 PPM S57

S58

S59

S60

S61

S62

11.827 10.314 10.284 8.472 8.445 8.422 8.358 8.328 8.291 8.259 8.249 8.221 8.033 8.004 7.878 7.851 7.827 7.744 7.717 7.579 7.559 7.533 7.512 7.258 7.123 7.093 6.936 6.910 6.885 Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry 3.35 3.39 1.02 1.03 1.99 2.11 1.02 1.02 0.87 1.00 10 8 6 4 2 0-2 PPM S63

S64

S65

4. X-ray crystal structures of 3e X-ray crystal structure of 3e. Ellipsoid probability: 50%. S66