Supporting Information

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1 Supporting Information Rhodium(I)-Catalyzed Cyclization Reaction of o-alkynyl Phenols and Anilines. Domino Approach to 2,3-Disubstituted Benzofurans and Indoles. Naohiro Isono and Mark Lautens* Davenport Research Laboratories, Department of Chemistry, University of Toronto, Toronto, ntario, Canada M5S 3H6 General: Melting point were recorded using a Fisher-Johns melting point apparatus and are uncorrected. 1 H and 13 C NMR spectra were recorded using either Varian Mercury 300 MHz or Varian Mercury 400MHz spectrometers. 1 H spectra were referenced to tetramethylsilane (TMS, 0 ppm) and 13 C spectra were referenced to solvent carbons (77 ppm). IR spectra were obtained using a Shimadzu FTIR-8400S spectrometer as thin films on NaCl plates. High resolution mass spectra were obtained from a Micromass 70S-2 spectrometer (EI) or an ABI/Sciex Qstar mass spectrometer (ESI). Toluene, dioxane and tetrahydrofuran (THF) were distilled under nitrogen from Na/benzophenone immediately prior to use. Dichloromethane was passed through a column of activated alumina under nitrogen. All reagents were used as received from Sigma-Aldrich unless otherwise indicated. Analytical thin layer chromatography was performed with Silicycle TM normal phase 0.25 mm aluminum backed TLC plates. Purification of reaction products was generally done by flash chromatography with Silicycle TM Ultra-Pure mesh silica gel. All experiments were performed under anhydrous conditions under an atmosphere of argon unless otherwise noted. [Rh(cod)H] 2 was prepared from [Rh(cod)Cl] 2 by a literature procedure. 1 [Rh(cod)Cl] 2, [Rh(C) 2 acac] and PdCl 2 (PPh 3 ) 2 were purchased from Strem Chemicals, Inc. 2-phenylethynylphenol (1a), 2 2-(1-hexynyl)phenol (1b), 2 2-[(4-Methoxyphenyl)ethynyl]phenol (1c), 2 and N-[2-(1-Hexynyl)phenyl]methanesulfonamide (7) 3 were prepared as previously reported. 1. Uson, R.; ro, L.A.; Cabeza, J. A. Inorg. Synth. 1985, 23, Yoneda, E.; Sugioka, T.; Hirao, K.; Zhang, S.-W.; Takahashi, S. J. Chem. Soc., Perkin Trans. 1, 1998, Hiroya,K.; Itoh, S.; Sakamoto, T. J. rg. Chem. 2004, 69, S1

2 1-(Methoxymethoxy)-2-[(3-fluoro)ethynyl]benzene (13). PdCl 2 (PPh 3 ) 2 (51 mg, 2 mol%) and CuI (16 mg, 2 mol%) were added to a solution of 1-ethynyl-3-fluorobenzene (0.45 ml, 5 eq.) and F MM 2-(Methoxymethoxy)iodobenzene 4 (0.98 g, eq.) in triethylamine ( ml). The resulting mixture is stirred at C for 1 h. The mixture is allowed to cool to room temperature, hexane was added, and the mixture is filtered through Celite. Removal of the solvent under reduced pressure affords a residue. Chromatography on silica gel using hexane-et 2 (10:1 v/v) gave 13 as a yellow oil (0.876 g, 93%). 1 H NMR (400 MHz, CDCl 3 ): δ 7.49 (dd, J = 7.6, 1.7 Hz, 1H), (m, 4H), 7.14 (dd, J = 8.3, 0.9 Hz, 1H), (m, 2H), 5.28 (s, 2H), 3.54 (s, 3H); 13 C NMR ( MHz, CDCl 3 ): δ (d, J = Hz), 157.8, 133.5, 130.0, (d, J C-F = 8.7 Hz), (d, J C-F = 3.2 Hz), (d, J C-F = 9.7 Hz), 121.9, (d, J C-F = 22.6 Hz), (d, J C-F = 21.2 Hz), 115.3, 113.4, 9, 91.9 (d, J C-F = 3.5 Hz), 86.7, 56.2; IR (neat): 3073, 2957, 2212, 1608, 1595, 1578, 1495, 1481, 14, 1441, 1404, 1304, 1277, 1263, 1234, 1198, 1153, 1126, 1101, 1080, 1044, 991 cm -1 ; HRMS (EI): Calc d for C 16 H 13 2 F [M + ]: 25900; found = [(3-fluoro)ethynyl]phenol (1d). A mixture of 13 (0.87 g, 3.4 mmol) and conc. HCl (0.70 ml) in MeH (7 ml) was stirred for 8.5 h at room temperature. The acid was neutralized with saturated F H NaHC 3. After removal of the solvent, water was added to the residue. The resulting mixture was extracted with EtAc, and washed with brine and the extract was dried over Na 2 S 4. The solvent was removed under reduced pressure. Chromatography on silica gel using pentane CH 2 Cl 2 (2:1 v/v) gave 1c as a white solid (0.713 g, 99%). m.p. = C. 1 H NMR (400 MHz, CDCl 3 ): δ 7.42 (dd, J = 7.6, 1.7 Hz, 1H), (m, 4H), (m, 1H), 6.99 (dd, J = 8.4, 1.2 Hz, 1H), 6.92 (ddd, J = 7.6, 7.4, 1.2 Hz, 1H), 5.74 (s, 1H); 13 C NMR ( MHz, CDCl 3 ): δ (d, J C-F = Hz), 156.5, 131.8, 130.8, (d, J C-F = 8.6 Hz), (d, J C-F = Hz), (d, J C-F = 9.3 Hz), 120.5, (d, J C-F = 22.9 Hz), (d, J C-F = 21.2 Hz), 114.9, 109.1, 94.9 (d, J C-F = 3.4 Hz), 8; IR (neat): 3431, 3069, 2207, 1603, 1578, 1497, 1481, 1462, 1433, 1346, 1242, 1206, 1190, 1153, 1034, 941, 839 cm -1 ; HRMS (EI): Calc d for C 14 H 9 F [M + ]: 21637; found = Tsang, K. Y.; Brimble, M. A. Tetrahedron 2007, 63, S2

3 4-(2-Methoxymethoxyphenyl)but-3-yn-1-ol (14). PdCl 2 (PPh 3 ) 2 (65 mg, 2 mol%) and CuI (22 mg, 2.5 mol%) H MM were added to a solution of 3-butyn-1-ol (0.38 ml, 1.1 eq.) and 2-(Methoxymethoxy)iodobenzene 4 (1.20 g, eq.) in triethylamine (12 ml). The resulting mixture is stirred at 45 C for 1 h. The mixture is allowed to cool to room temperature, hexane was added, and the mixture is filtered through Celite. Removal of the solvent under reduced pressure affords a residue. Chromatography on silica gel using hexane-etac (10:1-1:1 v/v) gave the product as a yellow oil (0.815 g, 68%). 1 H NMR (400 MHz, CDCl 3 ): δ 7.38 (dd, J = 7.6, 1.7 Hz, 1H), 7.24 (ddd, J = 8.4, 7.4, 1.7 Hz, 1H), 7.10 (dd, J = 8.4, Hz, 1H), 6.95 (ddd, J = 7.6, 7.4, Hz, 1H), 5.25 (s, 2H), (m, 2H), 3.52 (s, 3H), 2.73 (t, J = 6.1 Hz, 2H), 2.26 (brs, 1H); 13 C NMR ( MHz, CDCl 3 ): δ 157.8, 133.2, 129.3, 121.8, 11, 113.7, 9, 90.6, 79.1, 6, 56.3, 24.2; IR (neat): 3406, 2955, 1597, 1573, 1491, 1441, 1404, 1254, 1229, 1198, 1153, 1115, 1080, 1045, 991 cm -1 ; HRMS (EI): Calc d for C 12 H 14 3 [M + ]: 20943; found = Benzoic acid 4-(2-methoxymethoxyphenyl)but-3-ynyl ester (15). To a solution of alcohol (0.155 g, 1 eq) in Bz MM CH 2 Cl 2 (5 ml) was added pyridine (0.16 ml, 3 eq) and benzoyl chloride (0.13 ml, 1.5 eq). The reaction mixture was stirred at room temperature for 4 h. After removal of the solvent, E 2 and water were added to the residue. The mixture was separated and the organic layer was washed with H 2, brine, dried over MgS 4. Removal of the solvent under reduced pressure affords a residue. Chromatography on silica gel using hexane-etac (10:1-6:1 v/v) gave the product as a colorless oil (0.226 g, 97%). 1 H NMR (400 MHz, CDCl 3 ): δ 9 (dd, J =, 1.4 Hz, 2H), (m, 1H), 7.44 (dd, J =, 7.4 Hz, 2H), 7.38 (dd, J = 7.6, 1.7 Hz, 1H), 7.23 (ddd, J =, 7.4, 1.7 Hz, 1H), 9 (dd, J =, Hz, 1H), 6.94 (ddd, J = 7.6, 7.4, Hz, 1H), 5.19 (s, 2H), 4.53 (t, J = Hz, 2H), 3.46 (s, 3H), 2.95 (t, J = Hz, 2H); 13 C NMR ( MHz, CDCl 3 ): δ 166.3, 157.7, 133.6, 13, 130.1, 129.6, 129.2, 128.3, 121.8, 115.2, 113.9, 94.9, 89.4, 78.2, 62.9, 56.1, 20.4; IR (neat): 2959, 2905, 1721, 1601, 1578, 1491, 1451, 1385, 1316, 1273, 1231, 1198, 1153, 1115, 1080, 1045, 1026, 995 cm -1 ; HRMS (EI): Calc d for C 19 H 18 4 [M + ]: ; found = Benzoic acid 4-(2-hydroxyphenyl)but-3-ynyl ester (1e). A mixture of 15 (0.225 g, 0.73 mmol) and conc. HCl Bz H (0.72 ml) in MeH (7.2 ml) was stirred for 8 h at room temperature. The acid was neutralized with saturated NaHC 3. After removal of the solvent, water was added to the residue. The resulting mixture was extracted with EtAc, and washed with brine and the extract was dried over Na 2 S 4. The solvent was removed under reduced pressure. Chromatography on silica gel using hexane EtAc (5:1 v/v) gave the product as a white solid (0.158 g, 82%). m.p. = C. 1 H NMR (400 MHz, CDCl 3 ): δ 8 (dd, J =, 1.5 Hz, 2H), (m, 1H), 7.45 (dd, J =, 7.4 Hz, 2H), 7.28 (dd, J = 7.6, 1.7 Hz, 1H), 7.21 (ddd, J = 8.2, 7.4, 1.7 Hz, 1H), 6.92 (dd, J = 8.2, Hz, 1H), 6.83 (ddd, J = 7.6, 7.4, S3

4 Hz, 1H), 0 (s, 1H), 4.58 (t, J = 6.5 Hz, 2H), 2.96 (t, J = 6.5 Hz, 2H); 13 C NMR ( MHz, CDCl 3 ): δ 166.7, 156.9, 133.2, 131.6, 130.0, 129.8, 129.7, 128.5, 120.1, 114.7, 109.5, 92.9, 76.5, 62.6, 20.6; IR (neat): 3435, 3063, 2907, 1717, 1603, 1576, 1487, 1452, 1385, 1341, 1316, 1275, 1238, 1177, 1153, 1117, 1071, 1026, 827 cm -1 ; HRMS (EI): Calc d for C 17 H 14 3 [M + ]: 26943; found = (2-Methoxymethoxyphenylethynyl)trimethylsilane (16). PdCl 2 (PPh 3 ) 2 (63 mg, 0.09 mmol) and CuI (31 mg, TMS MM 0.16 mmol) were added to a solution of trimethylacetylene (1.3 ml, 9.20 mmol) and 2-(Methoxymethoxy)iodobenzene 4 (1.61 g, 9 mmol) in triethylamine (15 ml). The resulting mixture is stirred at C for 40 min. The mixture is allowed to cool to room temperature, hexane was added, and the mixture is filtered through Celite. Removal of the solvent under reduced pressure affords a residue. Chromatography on silica gel using hexane Et 2 (20:1-8:1 v/v) gave the product as a colorless oil (1.40 g, 98%). 1 H NMR (400 MHz, CDCl 3 ): δ 7.45 (dd, J = 7.6, 1.8 Hz, 1H), 7.26 (ddd, J = 8.4, 7.6, 1.8 Hz, 1H), 8 (dd, J = 8.4, 1.1 Hz, 1H), 6.96 (ddd, J = 7.6, 7.6, 1.1 Hz, 1H), 5.25 (s, 2H), 3.54 (s, 3H), 0.27 (s, 9H); 13 C NMR ( MHz, CDCl 3 ): δ 158.1, 133.9, 129.8, 121.9, 115.7, 11, 101.2, 98.4, 95.2, 56.2, 0.0; IR (neat): 2959, 2828, 2158, 1597, 1574, 1487, 1404, 1248, 1196, 1153, 1109, 1082, 1044, 995, 924, 868, 843 cm -1 ; HRMS (EI): Calc d for C 13 H 18 2 Si [M + ]: ; found = But-3-en-1-ynyl-2-methoxymethoxybenzene (17). To a solution of 16 (0.98 g, 5.14 mmol) in MeH (25 ml) was added KF (6 g, 18.2 mmol). The reaction mixture was stirred for 4 hr at room temperature. Solvent was evaporated. H 2 and Et 2 were added and the mixture was separated. MM The organic layer was washed with brine, dried over MgS 4 and concerated to give a crude of terminal alkyne. To a mixture of Pd(PPh 3 ) 4 (41 mg, mmol) and CuI (20 mg, 0.10 mmol) were added Et 2 NH (3 ml) and a THF (1 ml) solution of the crude under an argon atmosphere at room temperature. The reaction mixture was cooled with ice water bath, and vinyl bromide in THF ( M, 4.3 ml, 4.3 mmol) was added. The resulting mixture is stirred at room temperature for 23 h. The mixture was poured into water, and extracted with Et 2. The organic layer was washed with H 2 and brine, and dried over MgS 4. Evaporation of the solvent gave an oil, the crude product was purified by column chromatography (hexane:et 2 = :1 10:1) to give 17 (0. g, 73% in 2 steps) as a colorless oil. 1 H NMR (400 MHz, CDCl 3 ): δ 7.42 (dd, J = 7.6, 1.7 Hz, 1H), 7.25 (ddd, J = 8.4, 7.4, 1.7 Hz, 1H), 7.11 (dd, J = 8.4, Hz, 1H), 6.96 (ddd, J = 7.6, 7.4, Hz, 1H), 6 (dd, J = 17.6, 11.1 Hz, 1H), 5.73 (dd, J = 17.6, Hz, 1H), 5.53 (dd, J = 11.1, Hz, 1H), 5.24 (s, 2H), 3.52 (s, 3H); 13 C NMR ( MHz, CDCl 3 ): δ 157.6, 133.5, 129.6, 126.6, 121.8, 117.4, 115.3, 113.7, 9, 9, 86.2, 56.2; IR (neat): 2957, 2905, 2828, 2209, 1591, 1574, 1489, 1451, 1441, 1404, 1310, 1261, 1231, 1198, 1153, 1117, 1082, 1044, 993, 922 cm -1 ; HRMS (EI): Calc d for C 12 H 12 2 [M + ]: 18837; found = S4

5 2-But-3-en-1-ynylphenol (1f). A mixture of 17 (0.498 g, 2.65 mmol) and conc. HCl (4 ml) in MeH (10.4 ml) was stirred for 4 h at room temperature. The acid was neutralized with saturated NaHC 3. H After removal of the solvent, water was added to the residue. The resulting mixture was extracted with EtAc, and washed with brine and the extract was dried over Na 2 S 4. The solvent was removed under reduced pressure. Chromatography on silica gel using hexane Et 2 (10:1 v/v) gave the product as a white solid (0.364 g, 96%) with data matching that previously reported. 5 m.p. = C. 1 H NMR (400 MHz, CDCl 3 ): δ 7.34 (dd, J = 7.6, 1.8 Hz, 1H), 7.24 (ddd, J = 8.4, 7.4, 1.8 Hz, 1H), 6.95 (dd, J = 8.4, 1.2 Hz, 1H), 6.87 (ddd, J = 7.6, 7.4, 1.2 Hz, 1H), 6 (dd, J = 17.6, 11.1 Hz, 1H), 5.78 (dd, J = 17.6, 1.9 Hz, 1H), 5.74 (brs, 1H), 5.60 (dd, J = 11.1, 1.9 Hz, 1H); 13 C NMR ( MHz, CDCl 3 ): δ 156.7, 131.6, 130.5, 127.7, 120.4, 116.5, 114.7, 109.4, 9, 83.7; IR (neat): 37, 3086, 3061, 3045, 3011, 2191, 1593, 1574, 1485, 1462, 1451, 1412, 1344, 1292, 1234, 1184, 1153, 1105, 1032 cm -1 ; HRMS (EI): Calc d for C 10 H 8 [M + ]: 14575; found = General procedure for the Rh(I)-catalyzed cyclization (General procedure A) To a round bottom flask equipped with a magnetic stir bar was added [Rh(C) 2 acac] (10 mol%), BINAP (11 mol%). The flask was flushed with argon gas, then toluene (0.7 ml) and water (0.2 ml) were added and the mixture was stirred at room temperature for 15 min. 1 (1 eq) was added as a solution in toluene (0.80 ml) and the reaction mixture was stirred at C for 1 h. Et 2 (5 ml) was added to the reaction mixture and it was filtered on a short silica gel pad, washed four portions of 5 ml of ether. The filtrate was concentrated under reduced pressure, then was applied to the top of a column of silica gel and purified by column chromatography to give the product. 2-Phenyl-1-benzofuran (2a). Using the general procedure A above with phenol 1a (.0 mg, mmol), followed by chromatography on silica gel using hexane Et 2 (20:1-10:1 v/v) gave compound 2a as a white solid (47.3 mg, 95%) with data matching that previously reported. 6 m.p. = C. 1 H NMR (400 MHz, CDCl 3 ): δ 7.87 (d, J = 8.4 Hz, 2H), 7.59 (d, J = 7.6 Hz, 1H), 7.53 (d, J = Hz, 1H), 7.45 (dd, J = 8.4, 7.4 Hz, 2H), 7.36 (t, J = 7.4 Hz, 1H), 7.29 (dd, J =, 7.3 Hz, 1H), 7.23 (dd, J = 7.6, 7.3 Hz, 1H), 3 (s, 1H); 13 C NMR ( MHz, CDCl 3 ): δ 155.9, 154.9, 130.5, 129.2, 128.8, 128.5, 124.9, 124.2, 122.9, 120.9, 111.1, Kawasaki, T.; Yamamoto, Y. J. rg. Chem. 2002, 67, (a) Kabalka, G. W.; Wang, L.; Pagni, R. M. Tetrahedron 2001, 57, (b) Becht, J. M.; Gissot, A.; Wagner, A.; Miokowski, C. Chem. Eur. J. 2003, 9, S5

6 2-n-Butyl-1-benzofuran (2b). Using the general procedure A above with phenol 1b (43.3 mg, mmol), followed by chromatography on silica gel using hexane Et 2 (20:1-10:1 v/v) gave compound n-bu 2b as a colorless oil (38.1 mg, 88%) with data matching that previously reported. 7 1 H NMR (400 MHz, CDCl 3 ): δ (m, 1H), (m, 1H), (m, 2H), 6.37 (s, 1H), 2.77 (t, J = 7.5 Hz, 2H), 1.73 (quint, J = 7.5 Hz, 2H), 1.43 (sext, J = 7.5 Hz, 2H), 0.96 (t, J = 7.5 Hz, 3H); 13 C NMR ( MHz, CDCl 3 ): δ 159.7, 154.6, 12, 12, 122.3, 120.1, 110.7, 101.7, 29.8, 28.1, 22.3, (4-Methoxyphenyl)-1-benzofuran (2c). Using the general procedure A above with phenol 1c (45.1 mg, mmol), followed by chromatography on silica gel using hexane CH 2 Cl 2 Et 2 Me (10:1:1 v/v) gave compound 2c as a white solid (41.3 mg, 92%) with data matching that previously reported. 6a m.p. = 148- C. 1 H NMR (400 MHz, CDCl 3 ): δ 7.80 (d, J = 8.9 Hz, 2H), 7.56 (dd, J = 7.2, Hz, 1H), 7. (dd, J =, 1.2 Hz, 1H), (m, 2H), 6.98 (d, J = 8.9 Hz, 2H), 6.89 (s, 1H), 3.87 (s, 3H); 13 C NMR ( MHz, CDCl 3 ): δ 160.0, 15, 154.7, 129.5, 126.4, 123.7, 133.3, 122.8, 120.5, 114.2, 11, 99.6, (3-Fluorophenyl)-1-benzofuran (2d). Using the general procedure A above with phenol 1d (4 mg, F mmol), followed by chromatography on silica gel using hexane Et 2 (10:1 v/v) gave compound 2d as a white solid (41.3 mg, 90%) with data matching that previously reported. 6a m.p. = C. 1 H NMR (400 MHz, CDCl 3 ): δ 7.64 (ddd, J = 7.8, 1.8, Hz, 1H), 7.60 (dd, J = 7.8, 1.3 Hz, 1H), 7.56 (ddd, J = 10.0, 2.3, 1.8 Hz, 1H), 7.53 (dd, J = 8.2, Hz, 1H), 7.41, (ddd, J = 7.8, 7.8, Hz, 1H), 7.31 (ddd, J = 8.2, 7.3, 1.3 Hz, 1H), 7.23 (ddd, J = 7.8, 7.3, Hz, 1H), 8 2 (m, 1H), 5 (s, 1H); 13 C NMR ( MHz, CDCl 3 ): δ (d, J C-F = Hz), 154.9, (d, J C-F = 3.2 Hz), (d, J C-F = 8.6 Hz), (d, J C-F = 8.6 Hz), 128.9, 124.7, 123.1, 121.1, (d, J C-F = Hz), (d, J C-F = 21.4 Hz), (d, J C-F = 23.7 Hz), 111.2, Benzoic acid 2-benzofuran-2-ylethyl ester (2e). Using the general procedure A above with phenol 1e (43.7 Bz mg, mmol), followed by chromatography on silica gel using hexane EtAc (20:1 8:1 v/v) gave compound 2e as a white solid (42.4 mg, 97%). m.p. = C. 1 H NMR (400 MHz, CDCl 3 ): δ 3 (d, J = 7.8 Hz, 2H), (m, 1H), 7. (dd, J = 7.4, 1.5 Hz, 1H), 7.44 (dd, J = 7.8, 1.4 Hz, 1H), 7.43 (dd, J = 7.8, 7.4 Hz, 2H), 7.24 (ddd, J = 7.8, 7.2, 1.5 Hz, 1H), 7.19 (ddd, J = 7.4, 7.2, 1.4 Hz, 1H), 6.54 (s, 1H), 4.68 (t, J = 6.6 Hz, 2H), 3.27 (t, J = 6.6 Hz, 2H); 13 C NMR ( MHz, CDCl 3 ): δ 166.4, 15, 154.8, 13, 130.0, 129.6, 128.7, 128.3, 123.6, 122.6, 120.5, 110.8, 103.5, 62.3, 28.3; IR (neat): 3061, 2962, 1722, 1601, 1586, 1454, 1316, 1275, 1175, 1115, 1071, 1026, 947, 802 cm -1 ; HRMS (EI): Calc d for C 10 H 8 [M + - BzH]:14575; found = T. Kitamura, L. Zheng, H. Taniguchi, Tetrahedron Lett. 1993, 34, S6

7 3-Deutero-2-phenyl-1-benzofuran (2a-d). Using the general procedure A above with phenol 1a (49.8 mg, D mmol), followed by chromatography on silica gel using hexane Et 2 (20:1 10:1 v/v) gave compound 2a-d as a white solid (44.1 mg, 88%, 93% D by 1 H NMR). m.p. = C. 1 H NMR (400 MHz, CDCl 3 ): δ 7.87 (d, J = 7.4 Hz, 2H), 7.58 (d, J = 7.6 Hz, 1H), 7.53 (d, J = 8.2 Hz, 1H), 7.45 (dd, J = 7.7, 7.4 Hz, 2H), 7.35 (t, J = 7.7 Hz, 1H), 7.28 (dd, J = 7.8, 7.4 Hz, 1H), 7.23 (dd, J = 7.6, 7.4 Hz, 1H); 13 C NMR ( MHz, CDCl 3 ): δ 155.8, 154.9, 130.4, 129.1, 128.7, 128.5, 124.9, 124.2, 122.9, 120.8, 111.1, (J C D = 26.7 Hz); IR (neat): 3066, 1553, 1470, 1454, 1269, 1207, 1069, 903 cm -1 ; HRMS (EI): Calc d for C 14 H 9 D [M + ]:19794; found = General procedure for the Rh(I)-catalyzed cyclization with electrophile. (General procedure B) To a round bottom flask equipped with a magnetic stir bar was added [Rh(cod)H] 2 (3mol%), BINAP (6.6 mol%). The flask was flushed with argon gas, then dioxane ( ml) and water (0.1 ml) were added and the mixture was stirred at room temperature for 15 min. electrophile (10 eq) was added and 1 (1 eq) was added as a solution in dioxane ( ml) and the reaction mixture was stirred at 90 C for 6 h. Et 2 (5 ml) was added to the reaction mixture and it was filtered on a short silica gel pad, washed four portions of 5 ml of ether. The filtrate was concentrated under reduced pressure, then was applied to the top of a column of silica gel and purified by column chromatography to give the product. General procedure for the Rh(I)-catalyzed cyclization with electrophile. (General procedure C, without BINAP) To a round bottom flask equipped with a magnetic stir bar was added [Rh(cod)H] 2 (3 mol%). The flask was flushed with argon gas, then dioxane ( ml), water (0.1 ml) and electrophile (10 eq) were added. And then 1 (1 eq) was added as a solution in dioxane ( ml) and the reaction mixture was stirred at 90 C for 6 h. Et 2 (5 ml) was added to the reaction mixture and it was filtered on a short silica gel pad, washed four portions of 5 ml of ether. The filtrate was concentrated under reduced pressure, then was applied to the top of a column of silica gel and purified by column chromatography to give the product. 3-(2-Phenylbenzofuran-3-yl)propionitrile (5a) and 3-(2-Phenylbenzofuran-3-yl)acrylonitrile (6a). Using the general procedure B above with phenol 1a (43.2 mg, mmol), acrylonitrile (0.145 ml, 2.20 mmol) followed by chromatography on silica gel using hexane Et 2 (20:1 3:1 v/v) gave compound 5a (.8 mg, CN 92%) and 6a (2.4 mg, 4.4%). (5a): white solid. m.p. = C. 1 H NMR (400 MHz, CDCl 3 ): δ 7.75 (d, J = 7.3 Hz, 2H), (m, 5H), 7.34 (ddd, J = 8.2, 7.2, 1.4 Hz, 1H), 7.29 (ddd, J = 7.6, 7.2, 1.4 Hz, 1H), 3.33 (t, J = 7.8 Hz, 2H), 2.75 (t, J = 7.8 Hz, 2H); 13 C NMR ( MHz, CDCl 3 ): δ 153.9, 152.1, 130.3, 12, 128.9, 128.9, 127.1, 124.9, 122.9, 11, 118.9, 112.1, 111.4, 20.8, 17.3; IR (neat): 3061, 2930, 2247, 1456, 1443, 1260, 1215, 1177, 1119, 1065, 7 cm -1 ; HRMS S7

8 (EI): Calc d for C 17 H 13 N [M + ]: 24997; found = CN (6a): white solid. m.p. = C. 1 H NMR (400 MHz, CDCl 3 ): δ (m, 3H), 7.69 (d, J = 16.6 Hz, 1H), (m, 4H), 7.42 (ddd, J = 7.7, 7.3, 1.5 Hz, 1H), 7.37 (ddd, J = 7.7, 7.3, 1.3 Hz, 1H), 8 (d, J = 16.6 Hz, 1H); 13 C NMR ( MHz, CDCl 3 ): δ 15, 154.5, 14, 130.3, 129.1, 129.1, 128.6, 125.9, 125.8, 124.2, 120.4, 118.7, 112.3, 111.9, 96.7; IR (neat): 3067, 2216, 1620, 1555, 1456, 1441, 1252, 1206, 1136, 1072, 961 cm -1 ; HRMS (EI): Calc d for C 17 H 11 N [M + ]: 24841; found = (2-Phenylbenzofuran-3-yl)pentan-3-one (5b). Using the general procedure C above with phenol 1a (41.8 CEt mg, mmol), ethyl vinyl ketone (0.21 ml, 2.11 mmol) followed by chromatography on silica gel using hexane Et 2 (20:1 5:1 v/v) gave compound 5b as a white solid (56.3 mg, 94%). m.p. = C. 1 H NMR (400 MHz, CDCl 3 ): δ 7.78 (d, J = 7.2 Hz, 2H), 7.55 (dd, J = 7.9, 1.2 Hz, 1H), (m, 3H), (m, 1H), 7.31 (ddd, J = 7.9, 7.2, 1.4 Hz, 1H), 7.25 (ddd, J = 7.4, 7.2, 1.2 Hz, 1H), 3.23 (t, J = Hz, 2H), 2.84 (t, J = Hz, 2H), 2.43 (q, J = 7.3 Hz, 2H), 6 (t, J = 7.3 Hz, 3H); 13 C NMR ( MHz, CDCl 3 ): δ 210.4, 153.9,.8, 13, 130.0, 128.7, 128.2, 126.7, 124.4, 122.5, 119.3, 114.8, 111.1, 41.6, 36.1, 18.3, 7.7; IR (neat): 2976, 2937, 1713, 1456, 1443, 1358, 1260, 1213, 1113, 1069, 1026 cm -1 ; HRMS (EI): Calc d for C 19 H 18 2 [M + ]: ; found = (2-Phenylbenzofuran-3-yl)propionic acid ethyl ester (5c) and 3-(2-Phenylbenzofuran-3-yl)acrylic acid ethyl ester (6c). To a round bottom flask equipped with a magnetic stir bar was added [Rh(cod)H] 2 (2.7 mg, 3 CEt mol%). The flask was flushed with argon gas, then DME ( ml), water (0.2 ml) and ethyl acrylate (0.044 ml, 2 eq) were added. And then 1a (39.4 mg, 1 eq) was added as a solution in DME ( ml) and the reaction mixture was stirred at 85 C for 6 h. Et 2 (5 ml) was added to the reaction mixture and it was filtered on a short silica gel pad, washed four portions of 5 ml of ether. The filtrate was concentrated under reduced pressure. Chromatography on silica gel using hexane Et 2 (20:1 8:1 CEt v/v) gave an inseparable mixture of 5c and 6c (.8 mg, 85.2%) as a colorless oil. 1 H NMR analysis revealed ratio of >20:1 for the saturated product 5c over the unsaturated product 6c. (5c): 1 H NMR (400 MHz, CDCl 3 ): δ 7.79 (d, J = 7.2 Hz, 2H), 7.58 (dd, J = 7.6, 1.3 Hz, 1H), (m, 3H), (m, 1H), 7.30 (ddd, J = 7.8, 7.4, 1.3 Hz, 1H), 7.25 (ddd, J = 7.6, 7.4, 1.2 Hz, 1H), 4.12 (q, J = 7.2 Hz, 2H), 3.28 (t, J = 8.2 Hz, 2H), 2.73 (t, J = 8.2 Hz, 2H), 1.21 (t, J = 7.2 Hz, 3H); 13 C NMR ( MHz, CDCl 3 ): δ 172.7, 153.9, 151.1, 13, 129.9, 128.8, 128.3, 126.9, 124.5, 122.5, 119.4, 114.3, 111.1, 60.6, 34.1, 19.8, (6c): 1 H NMR (400 MHz, CDCl 3 ): δ 2 (d, J = 1 Hz, 1H), 7.87 (dd, J = 7.1, 1.7 Hz, 1H), 7.76 (dd, J = 8.1, 1.3 Hz, 2H), (m, 4H), (m, 2H), 6.67 (d, J = 1 Hz, 1H), 4.30 (q, J = 7.1 Hz, 2H), 1.36 (t, J = 7.1 Hz, 3H); 13 C NMR ( MHz, CDCl 3 ): δ 167.2, 157.5, 154.4, 135.8, 129.7, 129.7, 128.9, 128.5, 126.7, 125.2, 123.7, 12, 119.2, 112.6, 111.5, 60.4, S8

9 3-(2-n-Butylbenzofuran-3-yl)propionitrile (5ba) and 3-(2-n-Butylbenzofuran-3-yl)acrylonitrile (6ba). Using the general procedure B above with phenol 1b (42 mg, mmol), acrylonitrile (0.16 ml, 2.43 mmol) followed by chromatography on silica gel using hexane Et 2 (20:1 8:1 v/v) gave compound 5ba (42.7 mg, CN n-bu 78%) and 6ba (2.8 mg, 5.2%). (5ba): colorless oil. 1 H NMR (400 MHz, CDCl 3 ): δ (m, 2H), (m, 2H), 1 (t, J = 7.3 Hz, 2H), 2.78 (t, J = 7.5 Hz, 2H), 2.64 (t, J = 7.5 Hz, 2H), 1.74 (quint, J = 7.5 Hz, 2H), 1.40 (sext, J = 7.5 Hz, 2H), 0.96 (t, J = 7.5 Hz, 3H); 13 C NMR ( MHz, CDCl 3 ): δ 156.1, 15, 128.2, 123.6, 122.4, 119.1, 118.1, 11, 110.7, 30.4, 26.1, 22.4, 20.2, 17.9, 13.8; IR (neat): 2957, 2932, 2862, 2247, 1626, 1456, 1424, 1379, 1325, 1279, 1256, 1211, 1171, 1103, 1065, 1030 cm -1 ; HRMS (EI): Calc d for C 15 H 17 N [M + ]: ; found = (6ba): CN n-bu yellow oil. 1 H NMR (400 MHz, CDCl 3 ): δ (m, 1H), (m, 1H), 7.47 (d, J = 16.5 Hz, 1H), (m, 2H), 5.90 (d, J = 16.5 Hz, 1H), 2.87 (t, J = 7.5 Hz, 2H), 1.75 (quint, J = 7.5 Hz, 2H), 1.41 (sext, J = 7.5 Hz, 2H), 0.96 (t, J = 7.5 Hz, 3H); 13 C NMR ( MHz, CDCl 3 ): δ 163.1, 154.3, 14, 125.2, 124.8, 123.8, 119.9, 118.9, 112.3, 111.5, 94.3, 30.3, 26.6, 22.3, 13.7; IR (neat): 2959, 2932, 2872, 2216, 1626, 1564, 1478, 1454, 1389, 1209, 1182, 1103, 957 cm -1 ; HRMS (EI): Calc d for C 15 H 15 N [M + ]: ; found = [2-(4-Methoxyphenyl)benzofuran-3-yl]propionitrile (5ca) and 3-[2-(4-Methoxyphenyl)benzofuran- 3-yl]acrylonitrile (6ca). Using the general procedure B above with phenol 1c (42.4 mg, mmol), acrylonitrile (0.125 ml, 1.90 mmol) followed by chromatography on silica gel using hexane EtAc (10:1 3:1 v/v) gave compound 5ca (47.8 mg, 91%) and 6ca (2.6 mg, %). (5ca): white solid. m.p. = C. 1 H NMR CN Me (400 MHz, CDCl 3 ): δ 7.68 (d, J = Hz, 2H), 7.53 (dd, J = 7.5, 1.5 Hz, 1H), 7. (dd, J = 7.6, 1.3 Hz, 1H), 7.32 (ddd, J = 7.6, 7.2, 1.5 Hz, 1H), 7.27 (ddd, J = 7.5, 7.2, 1.3 Hz, 1H), 4 (d, J = Hz, 2H), 3.88 (s, 3H), 3.29 (t, J = 7.7 Hz, 2H), 2.73 (J = 7.7 Hz, 2H); 13 C NMR ( MHz, CDCl 3 ): δ 160.1, 153.8, 152.3, 129.2, 128.5, 124.4, 122.9, 122.8, 119.1, 118.6, 114.4, 111.2, 110.8, 55.4, 20.8, 17.3; IR (neat): 2957, 2934, 2837, 2247, 1611, 8, 1454, 1298, 1252, 1177, 1098, 1032, 833 cm -1 ; HRMS (EI): Calc d for C 18 H 15 N 2 [M + ]: ; found = (6ca): white solid. m.p. = C. 1 H NMR (400 MHz, CDCl 3 ): δ 7.72 (dd, J =, 1.6 Hz, 1H), 7.67 (d, J CN Me = 8.9 Hz, 2H), 7.66 (d, J = 16.6 Hz, 1H), 7.55 (dd, J = 7.8, 1.4 Hz, 1H), 7.39 (ddd, J = 7.8, 7.3, 1.6 Hz, 1H), 7.36 (ddd, J = 7.3,, 1.4 Hz, 1H), 7 (d, J = 8.9 Hz, 2H), 4 (d, J = 16.6 Hz, 1H), 3.91 (s, 3H); 13 C NMR ( MHz, CDCl 3 ): δ 161.3, 158.4, 154.3, 142.2, 130.2, 126.1, 125.4, 124.1, 121.5, 120.2, 11, 114.6, 111.7, 111.3, 95.8, 55.5; IR (neat): 2934, 2839, 2214, 1607, 5, 1452, 1422, 1387, 1346, 1304, 1261, 1209, 1179, 1078, 1028 cm -1 ; HRMS (EI): Calc d for C 18 H 13 N 2 [M + ]: 27946; found = S9

10 3-[2-(3-Fluorophenyl)benzofuran-3-yl]propionitrile (5da) and 3-[2-(3-Fluorophenyl)benzofuran-3-yl] acrylonitrile (6da). Using the general procedure B above with phenol 1d (47.6 mg, mmol), acrylonitrile (0.145 ml, 2.20 mmol) followed by chromatography on silica gel using hexane EtAc (10:1 5:1 v/v) gave compound 5da (54.3 mg, 91%) and 6da (0.8 mg, 1.4%). (5da): white solid. m.p. = C. 1 H NMR (400 CN F MHz, CDCl 3 ): δ (m, 3H), (m, 2H), 7.35 (ddd, J = 8.2, 7.6, 1.4 Hz, 1H), 7.29 (ddd, J = 7.6, 7.2, Hz, 1H), 7.10 (dddd, J = 8.4, 8.2, 2.5, Hz, 1H), 3.29 (t, J = 7.6 Hz, 2H), 2.73 (t, J = 7.6 Hz, 2H); 13 C NMR ( MHz, CDCl 3 ): δ (d, J C-F = Hz), 153.9,.6 (d, J C-F = 2.7 Hz), (d, J C-F = 8.4 Hz), (d, J C-F = 8.4 Hz), 128.8, 125.3, 12, (d, J C-F = 3.2 Hz), 119.1, 118.8, (d, J C-F = 21.2 Hz), 11 (d, J C-F = 23.3 Hz), 11, 111.5, 20.7, 17.3; IR (neat): 3073, 2924, 2249, 1614, 1582, 1489, 1456, 1424, 1223, 878 cm -1 ; HRMS (EI): Calc d for C 17 H 12 FN [M + ]: 26903; found = (6da): yellow solid. 1 H NMR (400 MHz, CDCl 3 ): δ7.75 (dd, CN F J = 7.4, 1.1 Hz, 1H), 7.67 (d, J = 16.6 Hz, 1H), 7.59 (dd, J = 7.3, 1.2 Hz, 1H), 7.54 (ddd, J =, 7.6, 5.5 Hz, 1H), (m, 3H), 7.39 (ddd, J = 7.6, 7.4, 1.2 Hz, 1H), 7.23 (dddd, J = 8.4, 8.1, 2.6, 1.3 Hz, 1H), 6.11 (d, J = 16.6 Hz, 1H). 1-(2-n-Butylbenzofuran-3-yl)pentan-3-one (5bb). Using the general procedure C above with phenol 1b CEt n-bu (44.5 mg, mmol), ethyl vinyl ketone (0.25 ml, 2.51 mmol) followed by chromatography on silica gel using hexane Et 2 (20:1 8:1 v/v) gave compound 5bb as a colorless oil (46.4 mg, 70%). 1 H NMR (400 MHz, CDCl 3 ): δ (m, 2H), (m, 2H), 2.90 (t, J = 7.6 Hz, 2H), (m, 4H), 2.34 (q, J = 7.3 Hz, 2H), 1.68 (quint, J = 7.5 Hz, 2H), 1.38 (sext, J = 7.5 Hz, 2H), 4 (t, J = 7.5 Hz, 3H), 0.94 (t, J = 7.3 Hz, 3H); 13 C NMR ( MHz, CDCl 3 ): δ 210.6, 15, 153.9, 129.2, 123.1, 12, 118.6, 112.9, 110.7, 4, 36.2, 30.5, 2, 22.4, 17.7, 13.8, 7.7; IR (neat): 2957, 2934, 2872, 1717, 1628, 1456, 1377, 1360, 1256, 1211, 1169, 1113, 1055, 1013 cm -1 ; HRMS (EI): Calc d for C 17 H 22 2 [M + ]: ; found = [2-(4-Methoxyphenyl)benzofuran-3-yl]pentan-3-one (5cb). Using the general procedure C above with CEt Me phenol 1c (43.1 mg, mmol), ethyl vinyl ketone (0.19 ml, 1.91 mmol) followed by chromatography on silica gel using hexane Et 2 (20:1 5:1 v/v) gave compound 5cb as a white solid (53.9 mg, 91%). m.p. = C. 1 H NMR (400 MHz, CDCl 3 ): δ (d, J = 8.9 Hz, 2H), 7.52 (dd, J = 7.2, 1.5 Hz, 1H), 7.47 (dd, J = 7.4, 1.3 Hz, 1H), 7.28 (ddd, J = 7.4, 7.3, 1.5 Hz, 1H), 7.24 (ddd, J = 7.3, 7.2, 1.3 Hz, 1H), 1 (d, J = 8.9 Hz, 2H), 3.87 (s, 3H), 3.19 (t, J = 7.9 Hz, 2H), 2.82 (t, J = 7.9 Hz, 2H), 2.43 (q, J = 7.4 Hz, 2H), 5 (t, J = 7.4 Hz, 3H); 13 C NMR ( MHz, CDCl 3 ): δ 210.5, 159.6, 153.7, 15, 130.1, 128.2, 12, 123.6, 122.4, 119.1, 114.2, 113.2, 110.9, 55.3, 41.6, 36.1, 18.3, 7.7; IR (neat): 2974, 2935, 2837, 1715, 1613, 1510, 1456, 1298, 1252, 1179, 1113, 1094, 1030, 833 cm -1 ; HRMS (EI): Calc d for C 20 H 20 3 [M + ]: ; found = S10

11 1-[2-(3-Fluorophenyl)benzofuran-3-yl]pentan-3-one (5db). Using the general procedure C above with CEt F phenol 1d (44.7 mg, mmol), ethyl vinyl ketone (0.21 ml, 2.11 mmol) followed by chromatography on silica gel using hexane Et 2 (20:1 8:1 v/v) gave compound 5db as a white solid (53.9 mg, 86%). m.p. = C. 1 H NMR (400 MHz, CDCl 3 ): δ (m, 2H), 7.51 (ddd, J = 9.9, 2.5, 1.8 Hz, 1H), 7.49 (dd, J =, 1.2 Hz, 1H), 7.44 (ddd, J = 8.2, 7.8, Hz, 1H), 7.33 (ddd, J =, 7.4, 1.4 Hz, 1H), 7.26 (ddd, J = 7.4,, 1.2 Hz, 1H), 7 (dddd, J = 8.4, 8.2, 2.5, Hz, 1H), 3.23 (t, J = 7.8 Hz, 2H), 2.84 (t, J = 7.8 Hz, 2H), 2.43 (q, J = 7.3 Hz, 2H), 6 (t, J = 7.3 Hz, 3H); 13 C NMR ( MHz, CDCl 3 ): δ 210.1, (d, J C-F = Hz), 153.8, (d, J C-F = 2.6 Hz), 13 (d, J C-F = 8.5 Hz), (d, J C-F = 8.5 Hz), 129.8, 124.9, 122.7, (d, J C-F = Hz), 119.6, 115.8, (d, J C-F = 21.3 Hz), (d, J C-F = 23.4 Hz), 111.2, 41.4, 36.1, 18.3, 7.7; IR (neat): 2976, 2938, 1715, 1614, 1582, 1491, 1456, 1360, 1229, 1223, 1184, 1115, 880 cm -1 ; HRMS (EI): Calc d for C 19 H 17 F 2 [M + ]: ; found = (2-Vinylbenzofuran-3-yl)pentan-3-one (5fb). Using the general procedure C above with phenol 1f (45.1 CEt mg, mmol), ethyl vinyl ketone (0.31 ml, 3.11 mmol) followed by chromatography on silica gel using hexane Et 2 (20:1 8:1 v/v) gave compound 5fb as a colorless oil (53.3 mg, 75%). 1 H NMR (400 MHz, CDCl 3 ): δ 7.47 (dd, J = 7.6, 1.3 Hz, 1H), 7.41 (dd, J = 8.2, Hz, 1H), 7.26 (ddd, J = 8.2, 7.2, 1.3 Hz, 1H), 7.19 (ddd, J = 7.6, 7.2, Hz, 1H), 6.75 (dd, J = 17.3, 11.2 Hz, 1H), 5.92 (dd, J = 17.3, 1.5 Hz, 1H), 5.37 (dd, J = 11.2, 1.5 Hz, 1H), 2.99 (t, J = 7.7 Hz, 2H), 2.74 (t, J = 7.7 Hz, 2H), 2.37 (q, J = 7.3 Hz, 2H), 2 (t, J = 7.3 Hz, 3H); 13 C NMR ( MHz, CDCl 3 ): δ 210.2, 154.1,.4, 129.1, 124.8, 123.1, 122.4, 119.3, 116.4, 114.9, 11, 41.8, 36.2, 17.4, 7.7; IR (neat): 2974, 2938, 1715, 1614, 1456, 1414, 1360, 1258, 1115, 1013, 878 cm -1 ; HRMS (EI): Calc d for C 15 H 16 2 [M + ]: 228.1; found = n-Butyl-1-methanesulfonylindole (8). Using the general procedure A above with aniline 7 (54.1 mg, mmol) followed by chromatography on silica gel using hexane EtAc (10:1 5:1 v/v) gave n-bu N compound 8 as a white solid (.4 mg, 93%) with data matching that previously reported. 3,8 Ms m.p. = C. 1 H NMR (400 MHz, CDCl 3 ): δ (m, 1H), (m, 1H), (m, 2H), 6.46 (s, 1H), 0 (s, 3H), 2.96 (t, J = 7.6 Hz, 2H), 1.75 (quint, J = 7.6 Hz, 2H), 1.46 (sext, J = 7.6 Hz, 2H), 0.98 (t, J = 7.6 Hz, 3H); 13 C NMR ( MHz, CDCl 3 ): δ 142.5, 136.8, 129.8, 123.9, 123.6, 120.2, 114.1, 108.4, 40.3, 3, 28.6, 22.4, Hiroya, K.; Itoh, S.; Sakamoto, T. Tetrahedron 2005, 61, S11

12 2-n-Butyl-3-deutero-1-methanesulfonylindole (8-d). Using the general procedure A above with aniline 7 D (55.1 mg, mmol) followed by chromatography on silica gel using hexane EtAc (20:1 5:1 v/v) gave compound 8-d as a white solid (49.5 mg, 90%, 95% D by 1 n-bu H NMR). m.p. N Ms = C. 1 H NMR (300 MHz, CDCl 3 ): δ (m, 1H), (m, 1H), (m, 2H), 0 (s, 3H), 2.95 (t, J = 7.6 Hz, 2H), 1.75 (quint, J = 7.6 Hz, 2H), 1.46 (sext, J = 7.6 Hz, 2H), 0.98 (t, J = 7.6 Hz, 3H); 13 C NMR ( MHz, CDCl 3 ): δ 142.4, 136.8, 129.8, 123.9, 123.6, 120.2, 114.1, (J C D = 26.4 Hz), 40.3, 3, 28.5, 22.4, 13.9; IR (neat): 2959, 2932, 2872, 1559, 1452, 1366, 1327, 1223, 1169, 1, 1047, 1024, 961 cm -1. HRMS (EI): Calc d for C 13 H 16 DN 2 S [M + ]: ; found = (2-n-Butyl-1-methanesulfonylindol-3-yl)propionitrile (9a) and 3-(2-n-Butyl-1-methanesulfonylindol- 3-yl)acrylonitrile (18a). Using the general procedure B above with aniline 7 (49.5 mg, mmol), CN acrylonitrile (0.13 ml, 1.98 mmol) followed by chromatography on silica gel using hexane EtAc (10:1 3:1 v/v) gave compound 9a (52.8 mg, 88.1%) and 18a (1.9 mg, %). n-bu N (9a): white solid. m.p. = -101 C. 1 H NMR (400 MHz, CDCl 3 ): δ 8 3 (m, 1H), Ms (m, 1H), (m, 2H), 7 (t, J = 7.3 Hz, 2H), 2.99 (t, J = 7.6 Hz, 2H), 2.96 (s, 3H), 2.67 (t, J = 7.3 Hz, 2H), (m, 2H), 1.42 (sext, J = 7.4 Hz, 2H), 0.96 (t, J = 7.4 Hz, 3H); 13 C NMR ( MHz, CDCl 3 ): δ 139.6, 136.4, 129.3, 124.7, 123.9, 118.8, 117.9, 116.7, 114.9, 40.0, 33.1, 2, 22.7, 20.4, 17.9, 13.8; IR (neat): 2959, 2932, 2872, 2247, 1607, 1454, 1362, 1329, 1242, 1171, 1082, 970 cm -1 ; HRMS (EI): Calc d for C 16 H 20 N 2 2 S [M + ]: ; found = (18a): white solid. m.p. = C. 1 CN H NMR (400 MHz, CDCl 3 ): δ (m, 1H), (m, 1H), 7.54 (d, J = 16.7 Hz, n-bu 1H), (m, 2H), 5.98 (d, J = 16.7 Hz, 1H), 3.12 (s, 3H), 8 (t, J = 7.4 Hz, 2H), N Ms (m, 2H), (m, 2H), 0.97 (t, J = 7.4 Hz, 3H); 13 C NMR ( MHz, CDCl 3 ): δ 145.1, 141.4, 136.2, 126.6, 125.4, 124.8, 119.6, 118.8, 115.2, 114.6, 96.4, 41.4, 33.3, 2, 22.7, 13.7; IR (neat): 2959, 2932, 2872, 2214, 1616, 1452, 1368, 1329, 1175, 1090, 961 cm -1 ; HRMS (ESI): Calc d for C 16 H 19 N 2 2 S [M + ]: ; found = (2-n-Butyl-1-methanesulfonylindol-3-yl)pentan-3-one (9b). Using the general procedure C above with CEt aniline 7 (47.3 mg, mmol), ethyl vinyl ketone (0.19 ml, 1.91 mmol) followed by chromatography on silica gel using hexane EtAc (10:1 5:1 v/v) gave compound 9b as a n-bu N white solid (59.6 mg, 94.4%). m.p. = C. 1 H NMR (400 MHz, CDCl 3 ): δ (m, Ms 1H), (m, 1H), (m, 2H), (m, 4H), 2.92 (s, 3H), 2.71 (t, J = 7.7 Hz, 2H), 2.42 (q, J = 7.3 Hz, 2H), 1.63 (quint, J = 7.5 Hz, 2H), 1.41 (sext, J = 7.5 Hz, 2H), 6 (t, J = 7.3 Hz, 3H), 0.94 (t, J = 7.5 Hz, 3H); 13 C NMR ( MHz, CDCl 3 ): δ 210.3, 138.1, 136.3, 130.2, 124.2, 123.6, 119.4, 118.4, 114.6, 4, 39.8, 36.1, 3, 25.8, 22.7, 18.3, 13.8, 7.7; IR (neat): 2959, 2934, 2872, 1713, 1607, 1454, 1412, 1362, 1240, 1171, 1153, 1113, 1067, 964 cm -1 ; HRMS (ESI): Calc d for C 18 H 26 N 3 S [M+H + ]: ; found = S12

13 3-(2-n-Butyl-1-methanesulfonylindol-3-yl)propionic acid ethyl ester (9c) and 3-(2-n-Butyl-1-methane sulfonylindol-3-yl)acrylic acid ethyl ester (18c). To a round bottom flask equipped with a magnetic stir bar was added [Rh(cod)H] 2 (2.6 mg, 3 mol%). The flask was flushed with argon gas, then dioxane ( ml), water (0.1 ml) and ethyl acrylate (0.042 ml, 2 eq) were added. And then 7 (4 mg, 1 eq) was added as a solution in dioxane ( ml) and the reaction mixture was stirred at 90 C for 4 h. Et 2 (5 ml) was added to the reaction mixture and it was filtered on a short silica gel pad, washed four portions of 5 ml of ether. The filtrate was concentrated under reduced pressure. Chromatography on silica gel using hexane EtAc (10:1 5:1 v/v) gave a mixture of 9c and 18c (61.3 mg, 91.3%). 1 H NMR analysis revealed ratio of >20:1 for the saturated product 9c over the unsaturated product 18c. (9c): colorless oil. 1 H NMR (400 MHz, CDCl 3 ): δ (m, 1H), (m, 1H), (m, 2H), 4.13 (q, J = 7.2 Hz, 2H), 1 (t, J = Hz, 2H), 2.95 CEt (t, J = 7.8 Hz, 2H), 2.92 (s, 3H), 2.60 (t, J = Hz, 2H), (m, 2H), 1.41 (sext, J = n-bu 7.4 Hz, 2H), 1.24 (t, J = 7.2 Hz, 3H), 0.95 (t, J = 7.4 Hz, 3H); 13 C NMR ( MHz, CDCl 3 ): N Ms δ 172.7, 138.4, 136.4, 130.2, 124.3, 123.6, 119.1, 118.5, 114.6, 60.6, 39.8, 34.4, 3, 25.9, 22.7, 19.7, 14.2, 13.8; IR (neat): 2959, 2932, 2872, 1732, 1607, 1454, 1362, 1242, 1171, 1119, 1080, 1047, 1020, 974 cm -1 ; HRMS (ESI): Calc d for C 18 H 26 N 4 S [M+H + ]: ; found = (18c): white solid. m.p. = C. 1 CEt H NMR (400 MHz, CDCl 3 ): (m, 1H), (m, 1H), 7.88 (d, J = 16.2 Hz, 1H), (m, 2H), 6.58 (d, J = 16.2 Hz, 1H), 4.30 (q, J = 7.2 Hz, n-bu 2H), 3.15 (t, J = 7.8 Hz, 2H), 9 (s, 3H), (m, 2H), (m, 2H), 1.37 (t, J = N Ms 7.2 Hz, 3H), 0.96 (t, J = 7.4 Hz, 3H); 13 C NMR ( MHz, CDCl 3 ): δ 167.4, 144.8, 136.3, 135.3, 127.5, 12, 124.5, 120.2, 118.7, 115.9, 114.4, 60.5, 4, 33.2, 25.9, 22.6, 14.4, 13.7; IR (neat): 2959, 2932, 2874, 1705, 1628, 1452, 1366, 1306, 1277, 1169, 1088, 1034, 1011, 972 cm -1 ; HRMS (ESI): Calc d for C 18 H 23 N 4 SNa [M+Na + ]: ; found = S13

14 Alkynylphenol 10 was prepared according to Scheme 1 using a modified variant of the method reported by Mori. 9 I MM H PdCl 2 (PPh 3 ) 2 ( mol %) CuI(mol%),Et 3 N THF, rt 67% H PCC, Celite MM CH 2 Cl 2,rt,5hr MM 19 92% 20 H Ph H 3 P C 2 Me CH MM 2 Cl 2,rt MM 20 52% 21 + C 2Me c.hcl C 2Me MeH, rt 93% H 10 Scheme 1 6-(2-Methoxymethoxyphenyl)hex-5-yn-1-ol (19). PdCl 2 (PPh 3 ) 2 (78 mg, 2 mol%) and CuI (28 mg, 3 mol%) H MM were added to a solution of 5-Hexyn-1-ol (0.62 ml, 1.1 eq.) and 2-(Methoxymethoxy)iodobenzene 4 (1.35 g, eq.) in triethylamine (7 ml). The resulting mixture is stirred at C for 0.5 h. The mixture is allowed to cool to room temperature, tertbutyl methyl ether was added, and the mixture is filtered through Celite. Removal of the solvent under reduced pressure affords a residue. Chromatography on silica gel using n-pentane-etac (10:1-1:1 v/v) gave 19 as a yellow oil (0.807 g, 67%). 1 H NMR (400 MHz, CDCl 3 ): δ 7.37 (dd, J = 7.6, 1.8 Hz, 1H), 7.22 (ddd, J = 7.6, 7.4, 1.8 Hz, 1H), 9 (dd, J = 7.6, Hz, 1H), 6.94 (ddd, J = 7.6, 7.4, Hz, 1H), 5.25 (s, 2H), 3.74 (dt, J =, 5.7 Hz, 2H), 3.52 (s, 3H), 2.52 (t, J = 6.6 Hz, 2H), (m, 4H), 1.46 (t, J = 5.7 Hz, 1H); 13 C NMR ( MHz, CDCl 3 ): δ 157.5, 133.4, 128.8, 121.8, 115.2, 114.3, 9, 94.1, 7, 62.3, 56.2, 31.8, 24.9, 19.4; IR (neat): 3734, 2939, 2232, 1597, 1575, 1489, 14, 1404, 1311, 1279, 1256, 1229, 1198, 1153, 1114, 1080, 1045, 994, 923 cm -1 ; HRMS (EI): Calc d for C 14 H 18 3 [M + ]: ; found = Nishida, M.; Adachi, N.; nozuka, K.; Matsumura, H.; Mori, M. J. rg. Chem. 1998, 63, S14

15 6-(2-Methoxymethoxyphenyl)hex-5-ynal (20). Dess-Martin periodinane (0.725 g, 1.71 mmol, 1.5 equiv) was H MM added to a solution of alcohol 19 (270 mg, mmol, equiv) in CH 2 Cl 2 (12 ml) at room temperature. After stirring for 5 h, the reaction mixture was put directly on column chromatography using hexane-etac (10:1-4:1) to yield aldehyde 20 (259 mg, 1.11 mmol, 97%) as a colorless oil. 1 H NMR (400 MHz, CDCl 3 ): δ 9.86 (t, J = 1.5 Hz, 1H), 7.37 (dd, J = 7.6, 1.7 Hz, 1H), 7.23 (ddd, J = 8.4, 7.4, 1.7 Hz, 1H), 9 (dd, J = 8.4, Hz, 1H), 6.94 (ddd, J = 7.6, 7.4, Hz, 1H), 5.24 (s, 2H), 3.52 (s, 3H), 2.69 (dt, J = 7.2, 1.5 Hz, 2H), 2.55 (t, J = 6.8 Hz, 2H), 1.96 (tt, J = 7.2, 6.8 Hz, 2H); 13 C NMR ( MHz, CDCl 3 ): δ 20, 157.7, 133.4, 12, 121.8, 115.1, 114.1, 94.9, 92.8, 77.9, 56.2, 42.7, 21.2, 19.1; IR (neat): 2955, 2828, 2232, 1715, 1597, 1489, 1454, 1404, 1310, 1251, 1231, 1198, 1153, 1113, 1080, 1045, 993, 922 cm -1 ; HRMS (EI): Calc d for C 14 H 16 3 [M + ]: ; found = (2-Methoxymethoxyphenyl)oct-2-en-7-ynoic acid methyl ester (21). The solution of aldehyde 20 (73 mg, C 2 Me MM mmol) in CH 2 Cl 2 ( ml) was added Methyl(triphenylphosphoranylidene)acetate (139 mg, 1.3 eq) at room temperature. The mixture was stirred at room temperature for 4.5 h. The reaction mixture was concentrated and purified by chromatography on silica gel using hexane EtAc (10:1 5:1 v/v) to give compound 21 (47 mg, 51.6%) as a colorless oil. 1 H NMR (400 MHz, CDCl 3 ): δ 7.37 (dd, J = 7.6, 1.7 Hz, 1H), 7.22 (ddd, J = 8.4, 7.4, 1.7 Hz, 1H), 9 (dd, J = 8.4, Hz, 1H), 0 (dt, J = 15.7, 7.1 Hz, 1H), 6.94 (ddd, J = 7.6, 7.4, Hz, 1H), 5.91 (dt, J = 15.7, 1.6 Hz, 1H), 5.24 (s, 2H), 3.73 (s, 3H), 3.52 (s, 3H), 2. (t, J = 7.1 Hz, 2H), 2.43 (ddt, J = 7.4, 7.1, 1.6 Hz, 2H), 1.79 (tt, J = 7.4, 7.1 Hz, 2H); 13 C NMR ( MHz, CDCl 3 ): δ 16, 157.6, 148.4, 133.4, 128.9, 121.7, 121.6, 115.1, 114.2, 94.9, 9, 77.6, 56.1, 51.4, 3, 2, 19.1; IR (neat): 2949, 2232, 1728, 1659, 1597, 1574, 1489, 1454, 1435, 1404, 1271, 1153, 1115, 1082, 1045, 995, 922 cm -1 ; HRMS (EI): Calc d for C 17 H 19 4 [M + -1]: ; found = (2-Hydroxyphenyl)oct-2-en-7-ynoic acid methyl ester (10). A mixture of 21 (0.298 g, 32 mmol) and C 2 Me H conc. HCl (0.5 ml) in MeH ( ml) was stirred for 6 h at room temperature. The acid was neutralized with saturated NaHC 3. After removal of the solvent, water was added to the residue. The resulting mixture was extracted with EtAc, and washed with brine and the extract was dried over Na 2 S 4. The solvent was removed under reduced pressure. Chromatography on silica gel using hexane EtAc (10:1-5:1 v/v) gave the product as a colorless oil (0.233 g, 93%). 1 H NMR (400 MHz, CDCl 3 ): δ 7.29 (dd, J = 7.6, 1.7 Hz, 1H), 7.21 (ddd, J = 8.2, 7.4, 1.7 Hz, 1H), 6.99 (dt, J = 15.6, Hz, 1H), 6.93 (dd, J = 8.2, 1.2 Hz, 1H), 6.85 (ddd, J = 7.6, 7.4, 1.2 Hz, 1H), 5.89 (dt, J = 15.6, 1.6 Hz, 1H), 5.72 (s, 1H), 3.73 (s, 3H), 2.53 (t, J = Hz, 2H), 2.40 (ddt, J = 7.4,, 1.6 Hz, 2H), 1.81 (tt J = 7.4, Hz, 2H); 13 C NMR ( MHz, CDCl 3 ): δ 166.9, 156.5, 14, 131.6, 129.7, 121.8, 120.2, 114.4, 109.9, 96.4, 75.4, 51.5, 31.2, 2, 1; IR (neat): 3417, 2949, 2224, 1722, 1658, 1602, 1574, 5, 1487, 1435, 1331, S15

16 1290, 1207, 1153, 1103, 1034, 978 cm -1 ; HRMS (EI): Calc d for C 15 H 16 3 [M + ]: ; found = (1,2,3,4-Tetrahydrodibenzofuran-1-yl)acetic acid methyl ester (11) and 6-Benzofuran-2-ylhex-2-enoic C 2 Me acid methyl ester (12). Using the general procedure C above with phenol 10 (45 mg, mmol) followed by chromatography on silica gel using hexane Et 2 (20:1 8:1 v/v) gave compound 11 (29.3 mg, 66%) and 12 (4.1 mg, 9.2%). (11): colorless oil. 1 H NMR (400 MHz, CDCl 3 ): δ 7.45, (dd, J = 7.2, 1.7 Hz, 1H), 7.40, (dd, J = 7.6, 1.6 Hz, 1H), 7.21 (ddd, J = 7.6, 7.4, 1.7 Hz, 1H), 7.18 (ddd, J = 7.4, 7.2, 1.6 Hz, 1H), 3.72 (s, 3H), (m, 1H), 2.94 (dd, J = 15.4, 4.3 Hz, 1H), (m, 2H), 2.42 (dd, J = 15.4, 10.1 Hz, 1H), (m, 3H), (m, 1H); 13 C NMR ( MHz, CDCl 3 ): δ 173.1, 154.4, 154.4, 127.6, 123.1, 122.2, 118.8, 114.9, 11, 51.6, 38.9, 2, 28.3, 23.4, 19.5; IR (neat): 2945, 1738, 1634, 1476, 1454, 1435, 1360, 1269, 1192, 1167, 1071, 1013, 910 cm -1 ; HRMS (ESI) Calcd for C 15 H 16 3 Na [M+Na + ]: 26991; found = (12): colorless oil. 1 H NMR (400 MHz, CDCl 3 ): δ 7.48 C 2 Me (dd, 7.5, 1.6 Hz, 1H), 7.41 (dd, 7.8, 1.2 Hz, 1H), 7.21 (ddd, J = 7.8, 7.2, 1.6 Hz, 1H), 7.18 (ddd, J = 7.5, 7.2, 1.2 Hz, 1H), 6.98 (dt, J = 15.6, Hz, 1H), 6.39 (s, 1H), 5.86 (dt,, J = 15.6, 1.5 Hz, 1H), 3.73 (s, 3H), 2.80 (t, J = 7.2 Hz, 2H), 2.31 (ddt, J = 7.6,, 1.5 Hz, 2H), 1.93 (tt, J = 7.6, 7.2 Hz, 2H); 13 C NMR ( MHz, CDCl 3 ): δ 16, 158.3, 154.7, 148.4, 128.8, 123.2, 122.5, 121.6, 120.2, 110.7, 102.4, 51.4, 31.4, 27.7, 2; IR (neat): 2949, 1728, 1659, 1603, 1587, 1456, 1435, 1275, 1198, 1175, 1148, 1084, 1042, 978 cm -1 ; HRMS (EI) Calcd for C 15 H 16 3 [M + ]: ; found = S16

17 1-(Methoxymethoxy)-2-[(3-fluoro)ethynyl]benzene (13). F MM S17

18 2-[(3-fluoro)ethynyl]phenol (1d). F H S18

19 4-(2-Methoxymethoxyphenyl)but-3-yn-1-ol (14). H MM S19

20 Benzoic acid 4-(2-methoxymethoxyphenyl)but-3-ynyl ester (15). Bz MM S20

21 Benzoic acid 4-(2-hydroxyphenyl)but-3-ynyl ester (1e). Bz H S21

22 (2-Methoxymethoxyphenylethynyl)trimethylsilane (16). TMS MM ppm (t1) 0 S22

23 1-But-3-en-1-ynyl-2-methoxymethoxybenzene (17). MM S23

24 2-But-3-en-1-ynylphenol (1f). H S24

25 2-Phenyl-1-benzofuran (2a). S25

26 2-n-Butyl-1-benzofuran (2b). n-bu S26

27 2-(4-Methoxyphenyl)-1-benzofuran (2c). Me S27

28 2-(3-Fluorophenyl)-1-benzofuran (2d). F S28

29 Benzoic acid 2-benzofuran-2-ylethyl ester (2e). Bz S29

30 3-Deutero-2-phenyl-1-benzofuran (2a-d). D 0.0 S30

31 3-(2-Phenylbenzofuran-3-yl)propionitrile (5a). CN S31

32 3-(2-Phenylbenzofuran-3-yl)acrylonitrile (6a). CN S32

33 1-(2-Phenylbenzofuran-3-yl)pentan-3-one (5b). CEt 200 S33

34 3-(2-Phenylbenzofuran-3-yl)propionic acid ethyl ester (5c) and 3-(2-Phenylbenzofuran-3-yl)acrylic acid ethyl ester (6c). (Table 2, entry 4) CEt S34

35 3-(2-Phenylbenzofuran-3-yl)propionic acid ethyl ester (5c) and 3-(2-Phenylbenzofuran-3-yl)acrylic acid ethyl ester (6c). (Table 2, entry 5) CEt ppm (t1) S35

36 3-(2-n-Butylbenzofuran-3-yl)propionitrile (5ba). CN n-bu S36

37 3-(2-n-Butylbenzofuran-3-yl)acrylonitrile (6ba). CN n-bu S37

38 3-[2-(4-Methoxyphenyl)benzofuran-3-yl]propionitrile (5ca). CN Me S38

39 3-[2-(4-Methoxyphenyl)benzofuran-3-yl]acrylonitrile (6ca). CN Me ppm (t1) ppm (t1) S39

40 3-[2-(3-Fluorophenyl)benzofuran-3-yl]propionitrile (5da). CN F S40

41 3-[2-(3-Fluorophenyl)benzofuran-3-yl] acrylonitrile (6da). CN F ppm (t1) S41

42 1-(2-n-Butylbenzofuran-3-yl)pentan-3-one (5bb). CEt n-bu 200 S42

43 1-[2-(4-Methoxyphenyl)benzofuran-3-yl]pentan-3-one (5cb). CEt Me 200 S43

44 1-[2-(3-Fluorophenyl)benzofuran-3-yl]pentan-3-one (5db). CEt F 200 S44

45 1-(2-Vinylbenzofuran-3-yl)pentan-3-one (5fb). CEt 200 S45

46 2-n-Butyl-1-methanesulfonylindole (8). N Ms n-bu ppm (t1) S46

47 2-n-Butyl-3-deutero-1-methanesulfonylindole (8-d). D N Ms n-bu 0.0 S47

48 3-(2-n-Butyl-1-methanesulfonylindol-3-yl)propionitrile (9a). CN N Ms n-bu S48

49 3-(2-n-Butyl-1-methanesulfonylindol-3-yl)acrylonitrile (18a). CN N Ms n-bu ppm (t1) S49

50 1-(2-Butyl-1-methanesulfonylindol-3-yl)pentan-3-one (9b). CEt N Ms n-bu 200 S

51 3-(2-Butyl-1-methanesulfonylindol-3-yl)propionic acid ethyl ester (9c). CEt N Ms n-bu S51

52 3-(2-Butyl-1-methanesulfonylindol-3-yl)acrylic acid ethyl ester (18c). CEt N Ms n-bu S52

53 6-(2-Methoxymethoxyphenyl)hex-5-yn-1-ol (19). H MM S53

54 6-(2-Methoxymethoxyphenyl)hex-5-ynal (20). H MM 200 S54

55 8-(2-Methoxymethoxyphenyl)oct-2-en-7-ynoic acid methyl ester (21). C 2 Me MM S55

56 8-(2-Hydroxyphenyl)oct-2-en-7-ynoic acid methyl ester (10). C 2 Me H S56

57 (1,2,3,4-Tetrahydrodibenzofuran-1-yl)acetic acid methyl ester (11). C 2 Me S57

58 6-Benzofuran-2-ylhex-2-enoic acid methyl ester (12). C 2 Me S58