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1 UPPRTING INFRMATIN Application of a Rhodium-Catalyzed Addition/Cyclization equence Toward the ynthesis of Polycyclic eteroaromatics Nai-Wen Tseng and Mark Lautens* Davenport Laboratories, Chemistry Department, University of Toronto, Toronto, ntario, Canada, M5 36 General Experimental ynthesis of Boronate Esters Rhodium-Catalyzed Addition/Cyclization Reactions NMR epctra

2 General Experimental: 1, and 13 C NMR spectra were recorded using either 300 Mz, 400Mz or 500Mz spectrometers. 1 spectra were referenced to tetramethylsilane (TM, 0 ppm) or solvent protons (DM-d 6, 2.50 ppm) and 13 C spectra were referenced to solvent carbons (CDCl 3, 77 ppm or DM-d 6, ppm). IR spectra were obtained as thin films on NaCl plates. igh resolution mass spectra were obtained at 70eV for electron impact ionization or at a spray voltage of 5500 V for electrospray ionization Toluene, dioxane and tetrahydrofuran (TF) were distilled under nitrogen from Na/benzophenone immediately prior to use. Dichloromethane and benzene were distilled under nitrogen from Ca 2 immediately before use. All reagents were used as received unless otherwise indicated. Analytical thin layer chromatography was performed with normal phase 0.25 mm glass backed TLC plates. Purification of reaction products was generally done by flash chromatography with mesh silica gel. All experiments were performed under anhydrous conditions under an atmosphere of nitrogen unless otherwise noted. 3-Bromo-2-benzo[b]thiophenecarbaldehyde, 1 2,3-dibromobenzofuran, 2 2,3-dibromo- 1-methyl-1-indole 3 were prepared according to the literature procedure. 1. Björk, M.; Grivas,. J. eterocyclic Chem. 2006, 43, Benincori, T.; Brenna, E.; annicolò, F. ; Trimarco, L.; Antognazza, P.; Cesarotti, E.; Demartin, F. ; Pilati, T. J. rg. Chem. 1996, 61, Tang,.; Li, J.-.; Xiw, Y.-X.; Wang, N.-X. ynthesis 2007, Matsuda, T.; Makino, M.; Murakami, M. Angew. Chem. Int. Ed. 2005, 44,

3 B() 2 1 p-toluenesulfonic acid monohydrate (86 mg, 0.45 mmole) was added to a mixture of 3-bromo-2-benzo[b]thiophenecarbaldehyde 1 (2.17 g, 9.00 mmole), ethylene glycol (2 ml, mmole) in benzene (22 ml). The reaction mixture was refluxed and the water removed by a Dean-tark trap for 3 h. The mixture was then cooled to room temperature, diluted with Et 2, washed with water (3 20 ml) and saturated aqueous sodium bicarbonate solution. The organic layer was dried with Mg 4, filtered and concentrated in vacuo to afford crude 3-bromo-2-(2-dioxolanyl)thiophene. To a solution of crude 3-bromo-2-(2-dioxolanyl)thiophene (9.00 mmole) and triisopropylborate (2.2 ml, 9.55 mmole) in 30 ml of toluene and 7.5 ml of TF at -78 o C, was added a 1.6M solution of n-butyllithium in hexane (6 ml, 9.55 mmole). The reaction was stirred at -78 o C for 1 h, and then warmed to 25 o C for another 1 h. The reaction mixture was cooled to 0 o C and hydrolyzed with saturated aqueous ammonium chloride solution and 2N Cl aqueous solution and stirred at 0 o C for 30 min. The aqueous layer was extracted with Et 2 (3 15 ml), then the combined organic layers was extracted with 2N Na aqueous solution (3 15 ml). The combined aqueous layers were cooled to 0 o C and acidified with 2N Cl aqueous solution to p = 2. The precipitated boronic acid was collected by vacuum filtration, washed with water (3 10 ml), and dried in vacuo to afford 2-formyl-3- benzothiopheneboronic acid (1.49 g, 81%) as brown solid, m.p. = 130 o C (decomp.). 1 NMR (400 Mz, CDCl 3 ): δ 10.0 (s, 1), (m, 1), (m, 1), (m, 2), 7.17 (s, 2); 13 C NMR (75 Mz, DM-d 6 ): δ 186.7, 147.2, 142.7, 141.6, 127.9, 127.8, 125.0, 123.1; IR (neat): 3296, 1645, 1591, 1501, 1433, 1405, 1372, 1334, 1311, 1285, 1254, 1204, 1160, 1109, 1160, 1041, 940, 758, 721 cm -1 ; RM (EI) Calcd for C 9 6 B 3 [M- + ] , found B 1 2-Formyl-3-benzothiopheneboronic acid 1 (1.49 g, 7.22 mmole) and pinacol (939 mg, 7.94 mmole) were dissolved in benzene (24 ml). The mixture was refluxed and the water was removed by a Dean-tark trap for 6 h. The reaction mixture was cooled to 25 o C, dried with Mg 4, filtered and concentrated in vacuo to afford crude 3

4 intermediate. eparately, tert-butyl P,P-dimethylphosphonoacetate (1.7 ml, 8.30 mmole) was added dropwise to a suspension of Na (318 mg, 7.94 mmole) in TF (25 ml) at 0 o C, After stirring at 0 o C for 30 min, a solution of the crude intermediate in 20 ml of TF was added dropwise and the reaction was warm to 25 o C and stirred for 16 h. The reaction was quenched with saturated aqueous sodium bicarbonate solution and the aqueous layer was extracted with Et 2 (3 20 ml). The combined organic layers were dried with Mg 4, filtered, and concentrated in vacuo. Chromatography on silica gel using 10% Et 2 in hexane (R f = 0.43) gave title compound as a white solid (2.54 g, 91%), m.p. = o C. 1 NMR (400 Mz, CDCl 3 ): δ 8.59 (d, J = 15.8 z, 1), (m, 1), (m, 1), (m, 2), 6.31 (d, J = 15.8 z, 1), 1.55 (s, 9), 1.41 (s, 12); 13 C NMR (100 Mz, CDCl 3 ): δ 165.8, 150.9, 144.2, 139.9, 137.9, 126.3, 125.8, 124.7, 122.8, 121.7, 83.8, 80.4, 28.2, 24.9; IR (neat): 2977, 1707, 1621, 1500, 1458, 1430, 1371, 1280, 1233, 1142, 973, 857, 764, 735 cm -1 ; RM (EI) Calcd for C B 4 [M + ] , found B 4 2-Formyl-3-benzothiopheneboronic acid 1 (263 mg, 1.28 mmole) and pinacol (166 mg, 1.41 mmole) was dissolved in benzene (10 ml). The mixture was refluxed and the water was removed by a Dean-tark trap for 6 h. The reaction mixture was cooled to 25 o C, the trap was removed and methyl (triphenylphosphoranylidene)acetate (471 mg, 1.41 mmole) was added. The mixture was stirred at 25 o C for 16 h, then filtered through a pad of silica gel and the pad was washed with Et 2. The organic layer was dried with Mg 4, filtered and concentrated in vacuo. Chromatography on silica gel using 30% Et 2 in hexane (R f = 0.5) gave title compound as a yellow solid (200 mg, 45%), m.p. = o C. 1 NMR (400 Mz, CDCl 3 ): δ 8.68 (d, J = 15.8 z, 1), (m, 1), (m, 1), (m, 2), 6.39 (d, J = 15.8 z, 1), 3.82 (s, 3), 1.42 (s, 9); 13 C NMR (100 Mz, CDCl 3 ): δ 167.2, 150.3, 144.2, 140.0, 139.2, 126.4, 126.0, 124.8, 121.7, 120.2, 83.9, 51.8, 24.9; IR (neat): 2976, 2944, 1715, 1621, 1588, 1502, 1454, 1429, 1400, 1371, 1331, 1302, 1276, 1262, 1232, 1165, 1140, 1036, 1020, 974, 948, 922, 857, 840, 764, 737 cm -1 ; RM (EI) Calcd for C B 4 [M + ] , found

5 Br 2 3-Bromo-2-(cyclopropylidenemethyl)-1-benzothiophene 1 was prepared according to the previously reported procedure for the synthesis of 2-bromobenzylidenecyclopropane. 4 Using reaction condition described in literature with 3-bromo-2-benzo[b]thiophenecarbaldehyde (500 mg, 2.07 mmole) as the starting material, followed by chromatography on silica gel using 0.5% Et 2 in hexane gave title compound (286 mg, 52%) as white solid, m.p. = o C. 1 NMR (400 Mz, CDCl 3 ): δ 7.74 (dd, J = 18.6, 8.0 z, 2), (m, 2), (m, 1), (m, 2), (m, 2); 13 C NMR (100 Mz, CDCl 3 ): δ , , 137.1, 130.0, 125.3, 124.9, 122.8, 122.2, 112.0, 105.6, 4.7, 3.2; IR (neat): 3049, 2966, 2361, 2336, 1770, 1682, 1556, 1540, 1458, 1434, 1398, 1326, 1308, 1287, 1253, 1189, 1155, 1132, 998, 972, 919, 806 cm -1 ; RM (EI) Calcd for C 12 9 [M-Br + ] , found B 6 To a solution of 3-bromo-2-(cyclopropylidenemethyl)-1-benzothiophene (0.25 g, 0.94 mmole) and triisopropylborate (0.24 ml, 1.03 mmole) in 6 ml of toluene and 1.5 ml of TF at -78 o C, was added a 1.6M solution of n-butyllithium in hexane (0.65 ml, 1.03 mmole). The reaction was stirred at -78 o C for 30 min and pinacol (0.13 g, 1.13 mmole) was added at -78 o C. The reaction was protected from light (aluminum foil), warmed to 25 o C and stirred for 16 h. The reaction mixture was then diluted with Et 2, washed with saturated aqueous ammonium chloride solution, water and brine. The organic layer was dried with Mg 4, filtrated and concentrated in vacuo. Chromatography on silica gel using 2% Et 2 in hexane (R f = 0.39) gave 2-[2-(cyclopropylidenemethyl)-1-benzothien-3-yl]-4,4,5,5-tetramethyl-1,3,2- dioxaborolane (0.16 g, 55%) as a white solid, m.p. = o C. 1 NMR (400 Mz, CDCl 3 ): δ (m, 1), (m, 1), (m, 1), (m, 2), (m, 4), 1.41 (s, 12); 13 C NMR (100 Mz, CDCl 3 ): δ 156.7, 144.3, 139.5, 129.1, 125.4, 124.2, 124.0, 121.3, 114.8, 83.3, 25.0, 5.0, 3.2; IR (neat): 2977, 1508, 1456, 1376, 1332, 1286, 1233, 1142, 984, 860, 762, 735 cm -1 ; RM (EI) 5

6 Calcd for C B 2 [M + ] , found Br 3 3-Bromo-1-benzofuran-2-carbaldehyde was prepared according to the previously reported procedure 1 for the synthesis of 3-bromo-2-benzo[b]thiophenecarbaldehyde. Using reaction condition described in literature with 2,3-dibromobenzofuran 2 (2.12 g, 7.68 mmole) as starting material, followed by chromatography on silica gel using 10% Et 2 in hexane (R f = 0.49) gave the title compound (1.18 g, 68%) as yellow solid, m.p. = o C. 1 NMR (400 Mz, CDCl 3 ): δ (s, 1), (m, 1), (m, 2), (m, 1); 13 C NMR (100 Mz, CDCl 3 ): δ 178.2, 154.9, 147.4, 130.5, 127.3, 124.8, 122.0, 113.0, 110.3; IR (neat): 2842, 2355, 1674, 1608, 1557, 1541, 1441, 1326, 1288, 1260, 1198, 1020, 1000, 903, 871, 702, 668, 616 cm -1 ; RM (EI) Calcd for C 9 5 Br 2 [M + ] , found B() Formyl-3-benzofuranboronic acid was prepared according to the procedure for the synthesis of 2-formyl-3-benzothiopheneboronic acid 1. Using reaction condition described above with 3-bromo-1-benzofuran-2-carbaldehyde (1.14 g, 5.07 mmole) as starting material gave title compound (0.84 g, 87%) as orange solid, m.p. = 131 o C (decomp.). 1 NMR (400 Mz, CDCl 3 ): δ (s, 1), (m, 1), (m, 2), 7.40 (ddd, J = 8.1, 6.8, 1.2 z, 1), 7.02 (s, 2); 13 C NMR (100 Mz, DM-d 6 ): δ 182.2, 156.0, 155.1, 130.3, 128.9, 125.4, 123.9, 112.0; IR (neat): 3315, 3177, 1661, 1558, 1477, 1450, 1436, 1404, 1378, 1296, 1259, 1246, 1160, 1121, 1107, 943, 861, 849, 814, 764, 740 cm -1 ; RM (EI) Calcd for C 9 6 B 4 [M- + ] , found B 7 The title compound was prepared according to the procedure for the synthesis of 1. Using reaction condition described above with 2-formyl-3-benzofuranboronic acid 6

7 (0.60 g, 3.16 mmole) as starting material, followed by chromatography on silica gel using 10% Et 2 in hexane (R f = 0.56) gave title compound (0.81 g, 69%) as white solid, m.p. = o C. 1 NMR (400 Mz, CDCl 3 ): δ 7.99 (d, J = 15.8 z, 1), 7.93 (d, J = 7.8 z, 1), 7.44 (d, J = 8.2 z, 1), (m, 1), (m, 1), 6.22 (d, J = 15.8 z, 1), 1.55 (s, 9), 1.38 (s, 12); 13 C NMR (100 Mz, CDCl 3 ): δ 166.1, 160.0, 155.3, 131.8, 131.3, 126.1, 123.5, 123.2, 122.4, 110.8, 83.8, 80.5, 28.2, 24.9; IR (neat): 2979, 2357, 1709, 1639, 1548, 1478, 1450, 1426, 1403, 1391, 1380, 1367, 1306, 1256, 1246, 1185, 1145, 1107, 1028, 983, 921, 881, 854, 793, 777, 752, 668 cm -1 ; RM (EI) Calcd for C B 5 Na [M+Na + ] , found Br N 5 3-Bromo-1-methyl-1-indole-2-carbaldehyde was prepared according to the previously reported procedure 1 for the synthesis of 3-bromo-2-benzo[b] thiophenecarbaldehyde. Using reaction condition described in literature with 2,3-dibromo-1-methyl-1-indole 3 (1.59 g, 5.48 mmole) as starting material, followed by chromatography on silica gel using 30% C 2 Cl 2 in hexane (R f = 0.5) gave the title compound (0.94 g, 73%) as yellow solid, m.p. = o C. 1 NMR (400 Mz, CDCl 3 ): δ (s, 1), 7.69 (d, J = 8.2 z, 1), (m, 1), 7.38 (d, J = 8.6 z, 1), (m, 1), 4.08 (s, 3); 13 C NMR (100 Mz, CDCl 3 ): δ 182.6, 139.4, 130.0, 128.1, 126.1, , , 110.5, 106.0, 31.8; IR (neat): 2357, 2331, 1666, 1610, 1504, 1469, 1393, 1329, 1238, 1180, 1158, 1122, 1106, 948, 870, 737 cm -1 ; RM (EI) Calcd for C 10 8 BrN [M + ] , found B() 2 N 6 (2-Fromyl-1-methyl-1-indol-3-yl)boronic acid was prepared according to the procedure for the synthesis of 2-formyl-3-benzothiopheneboronic acid 1. Using reaction condition described above with 3-Bromo-1-methyl-1-indole-2- carbaldehyde (0.72 g, 3.01 mmole) as starting material gave title compound (0.61 g, 46%) as yellow solid, m.p. = 128 o C (decomp.). 1 NMR (400 Mz, DM-d 6 ): δ (s, 1), 8.37 (bs, 2), 8.06 (dt, J = 8.1, 1.0 z, 1), 7.59 (dt, J = 8.5, 0.8 z, 1), 7.40 (ddd, J = 8.4, 7.0, 1.2 z, 1), 7.06 (ddd, J = 8.1, 7.0, 1.0 z, 1), 4.07 (s, 7

8 3); 13 C NMR (100 Mz, DM-d 6 ): δ 186.0, 140.0, 139.4, 130.8, 126.2, 125.9, 120.7, 110.7, 31.5; IR (neat): 3315, 1648, 1509, 1458, 1421, 1385, 1342, 1304, 1241, 1204, 1128, 1077, 1010, 962, 931, 855, 814, 748 cm -1 ; RM (EI) Calcd for C 10 9 BN 3 [M- + ] , found B N 9 The title compound was prepared according to the procedure for the synthesis of 1. Using reaction condition described above with (2-Fromyl-1-methyl-1-indol-3-yl) boronic acid (0.23 g, 1.14 mmole) as starting material, followed by chromatography on silica gel using 20% Et 2 in hexane (R f = 0.48) gave title compound (0.40 g, 92%) as yellow solid, m.p. = o C. 1 NMR (400 Mz, CDCl 3 ): δ 8.21 (d, J = 16.4 z, 1), 8.10 (d, J = 8.0 z, 1), (m, 2), 7.16 (t, J = 7.0 z, 1), 6.48 (d, J = 16.6 z, 1), 3.87 (s, 3), 1.57 (s, 9), 1.39 (s, 12); 13 C NMR (100 Mz, CDCl 3 ): δ 166.3, 142.6, 139.9, 133.5, 132.5, 123.7, 123.3, 122.8, 120.8, 109.3, 83.0, 80.3, 31.9, 28.2, 25.0; IR (neat): 2972, 2923, 1703, 1622, 1495, 1468, 1408, 1388, 1368, 1316, 1285, 1256, 1235, 1205, 1165, 1137, 1103, 1010, 977, 909, 858, 780, 768, 748 cm -1 ; RM (EI) Calcd for C BN 4 [M + ] , found General Procedure for Rhodium-Catalyzed Cascade Addition/Cyclization Reactions: A solution of 0.3 ml of water and 3 ml of dioxane in a 5 ml 2-neck round bottom flask was purged with argon and stired for 10 min at 25 o C. [Rh(cod)Cl] 2 (3.0 mg, mmole), tri-tert-butylphosphonium tetrafluoroborate (3.5 mg, mmole) and sodium carbonate (42.4 mg, 0.40 mmole) were added to the solution and stirred at 25 o C for 10 min. To the bright yellow solution was added the alkene 2, followed by addition of the boronate ester (0.20 mmole) and the reaction mixture was stirred at 80 o C for 3 h. The reaction was quenched with brine, and the aqueous layer was extracted with Et 2 (3 15 ml). The combined organic layers were dried with Mg 4, filtrated and concentrated in vacuo. 8

9 3a Using the general procedure above with 1 (77.3 mg, 0.20 mmole) as boronate ester and norborene 2a (22.6 mg, 0.24 mmole) as alkene, followed by chromatography on silica gel using 5% Et 2 in hexane (R f = 0.43) gave compound 3a (59.6 mg, 84%) as white solid, m.p. = o C. 1 NMR (400 Mz, CDCl 3 ): δ 7.74 (d, J = 8.0 z, 1), 7.63 (d, J = 7.8 z, 1), (m, 1), (m, 1), (m, 1), 3.16 (d, J = 7.2 z, 1), 2.60 (dd, J = 15.6, 7.4 z, 1), 2.52 (dd, J = 15.6, 7.6 z, 1), 2.46 (d, J = 3.9 z, 1), 2.46 (d, J = 3.9 z, 1), 2.42 (dd, J = 7.0, 2.2 z, 1), (m, 2), 1.49 (s, 9), (m, 1), (m, 2), 1.07 (dt, J = 10.1, 1.4 z, 1); 13 C NMR (100 Mz, CDCl 3 ): δ 171.5, 146.4, 145.5, 141.7, 134.5, 124.0, 123.5, 123.3, 121.4, 80.7, 58.4, 50.0, 45.8, 43.3, 42.7, 39.6, 33.1, 28.9, 28.5, 28.1; IR (neat): 2949, 2870, 1726, 1455, 1432, 1392, 1366, 1294, 1249, 1151, 1018, 937, 849, 752, 731 cm -1 ; RM (EI) Calcd for C [M + ] , found b Using the general procedure above with 1 (77.3 mg, 0.20 mmole) as boronate ester and benzonorbornene 2b (54.0 mg, 0.38 mmole) as alkene, followed by chromatography on silica gel using 10% Et 2 in hexane (R f = 0.58) gave compound 3b (77.0 mg, 98%) as white solid, m.p. = o C. 1 NMR (400 Mz, CDCl 3 ): δ (m, 2), (m, 1), (m, 2), (m, 1), (m, 2), (m, 2), (m, 2), 2.64 (dd, J = 15.8, 7.2 z, 1), (m, 1), 2.56 (dd, J = 15.8, 7.8 z, 1), (m, 1), (m, 1), 1.52 (s, 9); 13 C NMR (100 Mz, CDCl 3 ): δ 171.3, 148.2, 147.8, 147.5, 145.3, 140.2, 134.3, 126.0, 125.9, 124.2, , , 121.4, 121.1, 120.9, 80.9, 57.5, 49.6, 49.0, 46.9, 44.6, 43.6, 43.2, 28.2; IR (neat): 2970, 2932, 1724, 1458, 1366, 9

10 1269, 1244, 1148, 945, 910, 845, 752, 735 cm -1 ; RM (EI) Calcd for C [M + ] , found c Using the general procedure above with 1 (77.3 mg, 0.20 mmole) as boronate ester and norbornadiene 2c (21.1 mg, 0.24 mmole) as alkene, followed by chromatography on silica gel using 5% Et 2 in hexane (R f = 0.43) gave compound 3c (52.0 mg, 76%) as white solid, m.p. = o C. 1 NMR (400 Mz, CDCl 3 ): δ 7.76 (d, J = 8.0 z, 1), 7.67 (d, J = 7.8 z, 1), 7.33 (td, J = 7.5, 1.1 z, 1), (m, 1), (m, 1), (m, 1), , (m, 1), 3.23 (d, J = 7.0 z, 1), 3.01 (s, 1), 2.84 (s, 1), 2.62 (dd, J = 15.8, 7.6 z, 1), 2.55 (dd, J = 15.8, 7.6 z, 1), (m, 1), 1.50 (s, 9), (m, 1), (m, 1); 13 C NMR (100 Mz, CDCl 3 ): δ 171.4, 147.4, 145.1, 140.7, 137.6, 137.0, 134.4, 124.1, 123.5, 123.4, 121.4, 80.8, 56.1, 47.6, 47.3, 44.7, 43.8, 43.3, 42.9, 28.1; IR (neat): 2972, 2932, 1726, 1603, 1466, 1454, 1433, 1393, 1368, 1325, 1260, 1246, 1234, 1150, 1040, 754, 733, 712 cm -1 ; RM (EI) Calcd for C [M + ] , found Me 2 C C 2 Me 3d Using the general procedure above with 1 (77.3 mg, 0.20 mmole) as boronate ester and 2d (50.0 mg, 0.24 mmole) as alkene, followed by chromatography on silica gel using 20% EtAc in hexane (R f = 0.35) gave compound 3d (76.6 mg, 84%) as yellow oil. 1 NMR (400 Mz, CDCl 3 ): δ 7.77 (d, J = 8.0 z, 1), 7.70 (d, J = 7.8 z, 1), 7.37 (td, J = 7.6, 1.1 z, 1), (m, 1), 3.86 (s, 3), 3.80 (s, 3), 3.56 (d, J = 7.2 z, 1), (m, 2), 3.30 (s, 1), 2.78 (d, J = 7.0 z, 1), 2.65 (d, J = 2.3 z, 1), 2.63 (d, J = 2.5 z, 1), (m, 1), 1.50 (s, 9), (m, 1); 13 C NMR (100 Mz, CDCl 3 ): δ 171.0, 165.1, 164.9, 147.7, 145.4, 145.1, 144.8, 139.2, 133.9, 124.3, 123.8, 123.5, 121.4, 81.1, 55.9, 52.1, 52.0, 50.8, 48.4, 47.4, 43.9, 10

11 43.2, 42.1, 28.1; IR (neat): 2978, 2951, 1732, 1717, 1622, 1456, 1435, 1393, 1368, 1337, 1269, 1227, 1190, 1152, 1094, 1015, 918, 783, 758, 733 cm -1 ; RM (EI) Calcd for C [M + ] , found PMB PMB 3e Using the general procedure above with 1 (77.3 mg, 0.20 mmole) as boronate ester and oxabicyclo 2e (87.2 mg, 0.22 mmole) as alkene, followed by chromatography on silica gel using 30% EtAc in hexane (R f = 0.48) gave compound 3e (114.3 mg, 88%) as yellow oil. 1 NMR (400 Mz, CDCl 3 ): δ 7.74 (d, J = 8.0 z, 1), 7.61 (d, J = 7.6 z, 1), 7.33 (td, J = 7.5, 1.1 z, 1), (m, 1), 7.23 (d, J = 8.2 z, 4), 6.88 (d, J = 8.0 z, 4), 4.45 (s, 2), 4.42 (d, J = 11.3 z, 1), 4.42 (s, 2), 4.38 (d, J = 11.3 z, 1), (s, 3), 3.807, (m, 1), (m, 1), 3.33 (td, J = 9.1, 2.3 z, 2), 2.75 (dd, J = 7.2, 3.1 z, 1), 2.61 (dd, J = 15.8, 7.2 z, 1), 2.52 (dd, J = 15.8, 7.8 z, 1), 2.35 (td, J = J = 9.1, 6.1 z, 1), 2.23 (td, J = 9.2, 5.9 z, 1), 1.44 (s, 9); 13 C NMR (100 Mz, CDCl 3 ): δ 171.0, 159.2, 147.1, 145.4, 139.1, 134.1, 130.4, 130.3, 129.4, 129.2, 124.2, 123.6, 123.4, 121.0, , , 85.2, 81.1, 81.0, 72.9, 68.4, 68.3, 60.4, 58.7, 55.3, 50.7, 45.5, 45.3, 45.0, 43.0, 28.0, 21.0, 14.2; IR (neat): 2976, 2934, 2859, 2837, 2361, 2332, 1722, 1613, 1514, 1464, 1568, 1302, 1248, 1173, 1152, 1088, 1036, 820, 756, 731 cm -1 ; RM (EI) Calcd for C [M-C ] , found TIP 3f Using the general procedure above with 1 (77.3 mg, 0.20 mmole) as boronate ester 11

12 and oxabicyclo 2f (62.1 mg, 0.20 mmole) as alkene, followed by chromatography on silica gel using 15% Et 2 in hexane (R f = 0.35) gave compound 3f (71.2 mg, 62%) as yellow solid, m.p. = o C. 1 NMR (400 Mz, CDCl 3 ): δ 7.75 (dt, J = 7.9, 0.9 z, 1), 7.50 (d, J = 7.6 z, 1), (m, 1), (m, 1), 4.29 (dd, J = 7.4, 2.9 z, 1), 4.13 (t, J = 3.8 z, 1), 4.10 (d, J = 3.5 z, 1), 3.97 (d, J = 3.1 z, 1), (m, 1), 3.40 (dd, J = 7.4, 3.3 z, 1), 2.67 (dd, J = 16.6, 6.4 z, 1), 2.50 (dd, J = 16.6, 8.6 z, 1), (m, 2), 1.50 (s, 9), 1.24 (d, J = 7.4 z, 3), (m, 2), 1.06 (d, J = 7.4 z, 3); 13 C NMR (100 Mz, CDCl 3 ): δ 171.2, 145.7, 145.5, 140.6, 134.4, 124.1, 123.6, 123.3, 120.6, 86.4, 81.6, 80.7, 74.1, 55.9, 47.0, 46.4, 43.0, 40.2, 39.8, 28.2, 18.72, 18.69, 14.0, 13.9; IR (neat): 2932, 2865, 1726, 1460, 1432, 1365, 1242, 1174, 1145, 1088, 1038, 1010, 959, 883, 848, 812, 787, 755, 728 cm -1 ; RM (EI) Calcd for C i [M + ] , found Boc N Boc N 3g Using the general procedure above with 1 (77.3 mg, 0.20 mmole) as boronate ester and diazabicyclo 2g (71.1 mg, 0.24 mmole) as alkene, followed by chromatography on silica gel using 20% EtAc in hexane (R f = 0.49) gave compound 3g (69.2 mg, 61%) as yellow solid, m.p. = o C. NMR run at 75 o C, 1 NMR (500 Mz, DM-d 6 ): δ 7.87 (d, J = 7.9 z, 1), 7.63 (d, J = 7.5 z, 1), 7.40 (t, J = 7.5 z, 1), 7.31 (t, J = 7.5 z, 1), 4.56 (s, 1), 4.52 (s, 1), 3.62 (s, 1), 3.36 (s, 1), 3.09 (s, 1), (m, 1), (m, 2), 1.51 (s, 9), 1.46 (s, 10), 1.43 (s, 9); 13 C NMR (125 Mz, DM-d 6 ): δ 169.8, 155.3, 147.0, 144.4, 137.9, 132.9, 124.2, 123.5, 123.3, 120.3, 80.1, 79.9, 62.8, 61.0, 54.8, 47.4, 42.3, 41.5, 31.6, 27.6, 27.5, 27.4; IR (neat): 2978, 2933, 1728, 1695, 1455, 1392, 1367, 1258, 1143, 1105, 919, 853, 754, 732 cm -1 ; RM (EI) Calcd for C N 2 6 [M + ] , found

13 Using the general procedure above with 4 (68.8 mg, 0.20 mmole) as boronate ester and norborene 2a (22.6 mg, 0.24 mmole) as alkene, followed by chromatography on silica gel using 5% Et 2 in hexane (R f = 0.30) gave compound 5 (44.9 mg, 76%) as yellow oil. 1 NMR (400 Mz, CDCl 3 ): δ 7.74 (d, J = 8.0 z, 1), 7.63 (d, J = 7.8 z, 1), (m, 1), (m, 1), 3.75 (s, 3), (m, 1), 3.17 (d, J = 7.2 z, 1), 2.66 (dd, J = 7.6, 4.5 z, 2), 2.46 (d, J = 3.7 z, 1), 2.39 (dd, J = 7.1, 2.3 z, 1), 2.27 (d, J = 3.7 z, 1), (m, 2), (m, 1), (m, 2), 1.07 (d, J = 10.2 z, 1); 13 C NMR (100 Mz, CDCl 3 ): δ 172.6, 145.9, 145.5, 141.9, 134.5, 124.1, 123.5, 123.4, 121.4, 58.7, 51.7, 50.0, 45.5, 42.6, 41.7, 39.6, 33.1, 28.9, 28.5; IR (neat): 3054, 2948, 1736, 1571, 1508, 1463, 1433, 1364, 1295, 1248, 1165, 1083, 1044, 1019, 984, 935, 896, 850, 802, 753, 732, 706, 679 cm -1 ; RM (EI) Calcd for C [M + ] , found Using the general procedure above with 7 (74.1 mg, 0.20 mmole) as boronate ester and norborene 2a (22.6 mg, 0.24 mmole) as alkene, followed by chromatography on silica gel using 5% Et 2 in hexane (R f = 0.38) gave compound 8 (10.8 mg, 17%) as colorless oil. 1 NMR (400 Mz, CDCl 3 ): δ (m, 2), (m, 2), (m, 1), 2.98 (d, J = 6.7 z, 1), 2.70 (dd, J = 15.1, 5.3 z, 1), (m, 1), 2.41 (dd, J = 14.9, 9.0 z, 1), 2.35 (d, J = 4.3 z, 1), 2.24 (d, J = 4.3 z, 1), (m, 2), 1.45 (s, 9), (m, 3), (m, 1); 13 C NMR (100 Mz, CDCl 3 ): δ 171.2, 163.6, 160.6, 125.8, 122.9, 122.8, 122.5, 119.0, 111.9, 80.6, 58.5, 45.4, 42.4, 41.2, 40.8, 39.4, 33.0, 29.1, 28.6, 28.1; IR (neat): 2950, 2870, 1728, 1630, 1477, 1446, 1391, 1367, 1257, 1154, 1010, 943, 846, 744 cm -1 ; RM (EI) Calcd for C [M + ] , found N 10 Using the general procedure above with 9 (76.7 mg, 0.20 mmole) as boronate ester 13

14 and norborene 2a (22.6 mg, 0.24 mmole) as alkene, followed by chromatography on silica gel using 10% Et 2 in hexane (R f = 0.41) gave compound 10 (32.3 mg, 45%) as yellow solid, m.p. = o C. 1 NMR (400 Mz, CDCl 3 ): δ 7.46 (d, J = 7.6 z, 1), (m, 1), 7.13 (td, J = 7.6, 1.1 z, 1), (m, 1), 3.65 (s, 3), (m, 1), 3.12 (d, J = 6.8 z, 1), 2.73 (dd, J = 14.6, 3.6 z, 1), 2.46 (d, J = 7.0 z, 1), 2.40 (dd, J = 14.6, 10.1 z, 1), 2.35 (d, J = 3.9 z, 1), 2.19 (d, J = 4.1 z, 1), (m, 3), 1.41 (s, 9), (m, 2), 0.98 (dt, J = 10.0, 1.5 z, 1); 13 C NMR (100 Mz, CDCl 3 ): δ 171.4, 146.7, 142.1, 123.5, 120.4, 120.3, 118.9, 118.6, 109.2, 80.6, 59.5, 47.3, 42.8, 42.0, 41.6, 40.0, 33.0, 30.6, 28.83, 28.79, 280.0; IR (neat): 2943, 2866, 1726, 1611, 1572, 1463, 1417, 1384, 1365, 1338, 1288, 1250, 1239, 1207, 1139, 1033, 1010, 973, 940, 925, 914, 878, 849, 822, 798, 763, 727 cm -1 ; RM (EI) Calcd for C N 2 [M + ] , found

15 B() Chemical hift (ppm) Chemical hift (ppm) 15

16 B Chemical hift (ppm) Chemical hift (ppm) 16

17 B Chemical hift (ppm) Chemical hift (ppm) 17

18 Br Chemical hift (ppm) Chemical hift (ppm) 18

19 B Chemical hift (ppm) Chemical hift (ppm) 19

20 Br Chemical hift (ppm) Chemical hift (ppm) 20

21 B() Chemical hift (ppm) Chemical hift (ppm) 21

22 B Chemical hift (ppm) Chemical hift (ppm) 22

23 Br N Chemical hift (ppm) Chemical hift (ppm) 23

24 B() 2 N Chemical hift (ppm) Chemical hift (ppm) 24

25 B N Chemical hift (ppm) Chemical hift (ppm) 25

26 3a Chemical hift (ppm) Chemical hift (ppm) 26

27 3b Chemical hift (ppm) Chemical hift (ppm) 27

28 3c Chemical hift (ppm) Chemical hift (ppm) 28

29 Me 2 C C 2 Me 3d Chemical hift (ppm) Chemical hift (ppm) 29

30 PMB PMB 3e Chemical hift (ppm) Chemical hift (ppm) 30

31 TIP 3f Chemical hift (ppm) Chemical hift (ppm) 31

32 Boc N Boc N 3g 32

33 Chemical hift (ppm) Chemical hift (ppm) 33

34 Chemical hift (ppm) Chemical hift (ppm) 34

35 N Chemical hift (ppm) Chemical hift (ppm) 35