Electronic Supplementary Information (ESI) Schwartz s reagent-mediated regiospecific synthesis of 2,3-disubstituted indoles from isatins A. Ulikowski and B. Furman* Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland. E-mail: furbar@icho.edu.pl 1. General Remarks.... 1 2. Experimental details and characterization data of oxindoles 2a-f... 2 2.1. 1-benzyl-3-hydroxy-3-methylindolin-2-one 2a... 2 2.2. 1-benzyl-3-hydroxy-3-phenylindolin-2-one 2b... 2 2.3. 1-benzyl-3-hydroxy-3-(4-methoxyphenyl)indolin-2-one 2c... 2 2.4. ethyl 4-(1-benzyl-3-hydroxy-2-oxoindolin-3-yl)benzoate 2d... 3 2.5. 4-(1-benzyl-3-hydroxy-2-oxoindolin-3-yl)benzonitrile 2e... 3 2.6. 1-benzyl-3-hydroxy-3-(2-nitrophenyl)indolin-2-one 2f... 4 3. Experimental details and characterization data of indoles 3a-f, 4a-f, 5a-f, 6a-f, 7a-d... 4 3.1. Indoles 3a-f.... 4 3.2. Indoles 4a-f.... 6 3.3. Indoles 5a-f.... 7 3.4. Indoles 6a-f.... 9 3.5. Indoles 7a-d.... 11 4. Experimental details and characterization data of tetrahydroquinoline 8... 13 5. Copies of 1 H- and 13 C-NMR spectra for compounds 2a-8... 14 6. References... 89 1. General Remarks. The reagents were purchased from Sigma Aldrich, Alfa Aesar or TCI Chemicals and used without further purification. All reactions involving air- and moisture-sensitive materials were carried out under argon atmosphere in oven-dried glassware with magnetic stirring. THF was distilled from Na and benzophenone. CH2Cl2 was distilled from CaH2. Column chromatography was performed with Kieselgel (230-400 mesh). Analytical TLC was performed with Silica gel 60 F254 aluminum plates (Merck) with visualization by UV light and charring with Pancaldi reagent ((NH4)6MoO4, Ce(SO4)2, H2SO4, H2O). NMR analyses were performed with Varian VNMRS 500 MHz and 600 MHz spectrometers. Chemical shifts are calibrated using residual solvents signals (CDCl3: δ (H)= 7.26, δ (C)= 77) or TMS and are reported in ppm. Infrared spectra (IR) were recorded on a FT-IR-1600-Perkin Elmer spectrophotometer and are reported in frequency of
absorption (cm -1 ). HRMS spectra were recorded on ESI-TOF Mariner spectrometer (Perspective Biosystem) and are given in m/z. Melting points were measured on Melting Point Meter MPM- H2 apparatus and are uncorrected. 2. Experimental details and characterization data of oxindoles 2a-f 2.1. 1-benzyl-3-hydroxy-3-methylindolin-2-one 2a To a solution of N-benzylisatin (1 g, 4.22 mmol) in THF (40 ml) cooled to 0 o C MeMgBr (1.7 ml, 5.1 mmol, 3M in Et2O) was added dropwise during 5 min. The reaction mixture was allowed to warm to RT over 1 hour. Saturated aqueous NH4Cl was added, the layers were separated and the aqueous layer extracted three times with diethyl ether (3x40 ml). The combined organic extracts were dried (Na2SO4) and evaporated under reduced pressure. The residue was purified by FCC using 40% ethyl acetate in hexanes as the eluent. Isolated yield 908 mg (85%). 1-benzyl-3-hydroxy-3-methylindolin-2-one 2a Yellow solid, m.p. 147-148 o C (lit. m.p. 146-148 o C 1 ); 1 H NMR (500 MHz, CDCl3) δ 7.42 (d, 1H), 7.30 (m, 5H), 7.20 (t, 1H), 7.07 (t, 1H), 6.72 (d, 1H), 4.89 (AB, 2H), 2.74 (br s, 1H), 1.67 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 178.6, 141.8, 135.4, 131.3, 129.5, 128.8, 127.6, 127.1, 123.4, 123.2, 109.5, 73.7, 43.7, 25.0. IR (film) ν : 3387, 2974, 1704, 1614, 1368, 1180, 753 cm -1 HRMS (ESI-TOF) m/z calcd for C16H15NO2Na [M+Na + ] 276,1000 Found: 276,0994. 2.2. 1-benzyl-3-hydroxy-3-phenylindolin-2-one 2b To a solution of N-benzylisatin (1 g, 4.22 mmol) in THF (40 ml) cooled to 0 o C PhMgBr (1.7 ml, 5.1 mmol, 3M in Et2O) was added dropwise during 5 min. The reaction mixture was allowed to warm to RT over 1 hour. Saturated aqueous NH4Cl was added, the layers were separated and the aqueous layer extracted three times with diethyl ether (3x40 ml). The combined organic extracts were dried (Na2SO4) and evaporated under reduced pressure. The residue was purified by FCC using 40% ethyl acetate in hexanes as the eluent. Isolated yield 998 mg (75%). 1-benzyl-3-hydroxy-3-phenylindolin-2-one 2b Yellow solid, m.p. 150-151 o C(lit. m.p. 150 o C 2 ); 1 H NMR (500 MHz, CDCl3) δ 7.46 7.39 (m, 2H), 7.39 7.25 (m, 9H), 7.23 (t, 1H), 7.05 (t, 1H), 6.79 (d, 1H), 4.94 (AB, 2H), 3.33 (br s, 1H). 13 C NMR (126 MHz, CDCl3) δ 177.5, 142.6, 140.1, 135.4, 131.5, 129.7, 128.8, 128.6, 128.3, 127.7, 127.2, 125.2, 124.9, 123.5, 109.7, 77.9, 44.0. IR (film) ν : 3375, 3060, 1705, 1613, 1372, 1170, 750, 696 cm -1 HRMS (ESI-TOF) m/z calcd for C21H17NO2Na [M+Na + ] 338,1157 Found: 338,1151. 2.3. 1-benzyl-3-hydroxy-3-(4-methoxyphenyl)indolin-2-one 2c To a solution of 4-iodoanisole (1.19 g, 5.1 mmol) in THF (20 ml) was added iprmgcl (2.81 ml, 2M in THF, 5.61 mmol) at RT. The solution was stirred for 1h and added dropwise during 5 min to a solution of N-benzylisatin (1 g, 4.22 mmol) in THF (20 ml) cooled to 0 o C. The reaction mixture was allowed to warm to RT over 1 hour. Saturated aqueous NH4Cl was added, the layers were separated and the aqueous layer extracted three times with diethyl ether (3x40 ml). The combined organic extracts were dried (Na2SO4) and evaporated under
reduced pressure. The residue was purified by FCC using 40% ethyl acetate in hexanes as the eluent. Isolated yield 1.02 g (70%). 1-benzyl-3-hydroxy-3-(4-methoxyphenyl)indolin-2-one 2c White solid, m.p. 159-160 o C; 1 H NMR (500 MHz, CDCl3) δ 7.39 7.25 (m, 8H), 7.22 (t, 1H), 7.05 (t, 1H), 6.91 6.84 (m, 2H), 6.77 (d, 1H), 4.92 (AB, 2H), 3.79 (s, 3H), 3.35 (s, 1H). 13 C NMR (126 MHz, CDCl3) δ 177.6, 159.6, 142.5, 135.4, 132.1, 131.5, 129.7, 128.8, 127.7, 127.2, 126.7, 124.9, 123.4, 114.0, 109.7, 77.5, 55.2, 44.0. IR (film) ν : 3397, 3060, 1705, 1612, 1510, 1252, 1175, 1031, 826, 751 cm -1 HRMS (ESI-TOF) m/z calcd for C22H19NO3Na [M+Na + ] 368,1263 Found: 368,1253. 2.4. ethyl 4-(1-benzyl-3-hydroxy-2-oxoindolin-3-yl)benzoate 2d To a solution of ethyl 4-iodobenzoate ( mol) in THF (20 ml) was added iprmgcl (2.81 ml, 2M in THF, 5.61 mmol) at -20 o C. The solution was stirred for 1h and added dropwise during 5 min to a solution of N-benzylisatin (1 g, 4.22 mmol) in THF (20 ml) cooled to -20 o C. The reaction mixture was allowed to warm to RT over 1 hour. Saturated aqueous NH4Cl was added, the layers were separated and the aqueous layer extracted three times with diethyl ether (3x40 ml). The combined organic extracts were dried (Na2SO4) and evaporated under reduced pressure. The residue was purified by FCC using 40% ethyl acetate in hexanes as the eluent. Isolated yield 1.08 g (66%). ethyl 4-(1-benzyl-3-hydroxy-2-oxoindolin-3-yl)benzoate 2d White solid, m.p. 151-152 o C; 1 H NMR (500 MHz, CDCl3) δ 8.00 (d, 2H), 7.46 (d, 2H), 7.39 7.20 (m, 7H), 7.04 (t, 1H), 6.82 (d, 1H), 4.94 (AB, 2H), 4.36 (q, J = 7.1 Hz, 2H), 3.59 (br s, 1H), 1.38 (t, J = 7.1 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 177.0, 166.1, 144.9, 142.6, 135.2, 131.2, 130.4, 130.0, 129.9, 128.9, 127.8, 127.3, 125.2, 124.9, 123.7, 109.9, 77.9, 61.0, 44.1, 14.3. IR (film) ν : 3398, 2981, 1715, 1613, 1278, 1105, 1020, 751 cm -1 HRMS (ESI-TOF) m/z calcd for C24H21NO4Na [M+Na + ] 410,1368 Found: 410,1360. 2.5. 4-(1-benzyl-3-hydroxy-2-oxoindolin-3-yl)benzonitrile 2e To a solution of 4-iodobenzonitrile (1.17 g, 5.1 mmol) in THF (20 ml) was added iprmgcl (2.81 ml, 2M in THF, 5.61 mmol) at -20 o C. The solution was stirred for 1h and added dropwise during 5 min to a solution of N-benzylisatin (1 g, 4.22 mmol) in THF (20 ml) cooled to -20 o C. The reaction mixture was allowed to warm to RT over 1 hour. Saturated aqueous NH4Cl was added, the layers were separated and the aqueous layer extracted three times with diethyl ether (3x40 ml). The combined organic extracts were dried (Na2SO4) and evaporated under reduced pressure. The residue was purified by FCC using 40% ethyl acetate in hexanes as the eluent. Isolated yield 1.02 g (71%). 4-(1-benzyl-3-hydroxy-2-oxoindolin-3-yl)benzonitrile 2e Off-white solid, m.p. 156-157 o C; 1 H NMR (500 MHz, CDCl3) δ 7.57 (d, 2H), 7.46 (d, 2H), 7.34 7.21 (m, 6H), 7.18 (d, 1H), 7.04 (t, 1H), 6.81 (d, 1H), 4.89 (AB, 1H), 3.84 (br s, 1H). 13 C NMR (126 MHz, CDCl3) δ 176.6, 145.3, 142.5, 135.0, 132.4, 130.8, 130.3, 128.9, 128.0, 127.3, 126.2, 124.9, 123.9, 118.4, 112.1, 110.0, 77.7, 44.2. IR (film) ν : 3395, 3060, 2229, 1708, 1611, 1468, 1370, 1172, 754, 736, 699 cm -1 HRMS (ESI-TOF) m/z calcd for C22H16N2O2Na [M+Na + ] 383,0992 Found: 383,0997.
2.6. 1-benzyl-3-hydroxy-3-(2-nitrophenyl)indolin-2-one 2f To a solution of 2-nitroiodobenzene (1.27 g, 5.1 mmol) in THF (20 ml) was added PhMgBr (1.87 ml, 3M in Et2O, 5.61 mmol) at -40 o C. The solution was stirred for 1h and added dropwise during 5 min to a solution of N-benzylisatin (1 g, 4.22 mmol) in THF (20 ml) cooled to -40 o C. The reaction mixture was allowed to warm to RT over 1 hour. Saturated aqueous NH4Cl was added, the layers were separated and the aqueous layer extracted three times with diethyl ether (3x40 ml). The combined organic extracts were dried (Na2SO4) and evaporated under reduced pressure. The residue was purified by FCC using 40% ethyl acetate in hexanes as the eluent. Isolated yield 1.17 g (77%). 1-benzyl-3-hydroxy-3-(2-nitrophenyl)indolin-2-one 2f Yellow solid, m.p. 177-178 o C; 1 H NMR (500 MHz, CDCl3) δ 8.32 (d, 1H), 7.89 (d, 1H), 7.73 (t, 1H), 7.51 (t, 1H), 7.40 (d, 2H), 7.35 (t, 2H), 7.32 7.19 (m, 2H), 7.05 (d, 1H), 6.96 (t, 1H), 6.79 (d, 1H), 4.99 (AB, 2H), 3.63 (br s, 1H). 13 C NMR (126 MHz, CDCl3) δ 175.3, 147.5, 143.9, 135.4, 133.8, 133.1, 130.3, 129.8, 129.4, 129.3, 128.8, 127.6, 127.3, 125.0, 123.5, 123.1, 109.8, 76.4, 44.2. IR (film) ν : 3382, 3060, 1956, 1702, 1613, 1525, 1356, 1189, 1025, 768, 751, 729 cm -1 HRMS (ESI-TOF) m/z calcd for C21H16N2O4Na [M+Na + ] 363,1109 Found: 363,1100. 3. Experimental details and characterization data of indoles 3a-f, 4a-f, 5a-f, 6a-f, 7a-d 3.1. Indoles 3a-f. To a suspension of Schwartz s reagent (1 equiv.) in THF (1 ml) cooled to -20 o C was added oxindole (50 mg). The reaction mixture was stirred at RT until it cleared. It was cooled to -20 o C and TFA (2 equiv.) and allyltributylstannane (3 equiv.) was added. The reaction mixture was stirred until TLC showed the reaction to be complete. The reaction was quenched with saturated NaHCO3 and ether (5 ml) was added. The aqueous layer was extracted twice with ether (2x5 ml) and the combined extracts washed three times with saturated NH4F. They were dried with Na2SO4 and evaporated. The crude was dissolved in CH2Cl2 (5 ml) and TFA (2 equiv.) was added at RT. When the dehydration was complete (TLC control), ethyl acetate (5 ml) was added and the reaction mixture evaporated under reduced pressure. The product was purified by FCC in the appropriate solvent system. 2-allyl-1-benzyl-3-methyl-1H-indole 3a This compound was synthesized according to the general procedure starting with 50 mg (0.198 mmol) of 2a and purified using 1% ethyl acetate in hexanes; Isolated yield 51 mg (99%); Colorless oil; 1 H NMR (600 MHz, CDCl3) δ 7.59 (m, 1H), 7.31 7.18 (m, 4H), 7.14 (m, 2H), 6.97 (d, 2H), 5.87 (m, 1H), 5.32 (s, 2H), 5.05 (dd, J = 10.1, 1.7 Hz, 1H), 4.97 (dd, J = 17.1, 1.7 Hz, 1H), 3.47 (d, 2H), 2.32 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 138.3, 136.5, 134.9, 133.5, 128.6, 128.5, 127.1, 125.9, 121.0, 118.8, 118.2, 115.9, 109.1, 108.1, 46.5, 28.8, 8.7. IR (film) ν : 3056, 1468, 1355, 1177, 914, 732, 697 cm -1 HRMS (ESI-TOF) m/z calcd for C19H19N [M + ] 261,1517 Found: 261,1521 2-allyl-1-benzyl-3-phenyl-1H-indole 3b This compound was synthesized according to the general procedure starting with 50 mg (0.159 mmol) of 2b and purified using 1-2% ethyl acetate in hexanes; Isolated yield 51 mg
(99%); Colorless oil; 1 H NMR (600 MHz, CDCl3) δ 7.76 (d, 1H), 7.63 7.54 (d, 2H), 7.48 (t, 2H), 7.34 (t, 1H), 7.32 7.23 (m, 4H), 7.23 7.14 (m, 2H), 7.02 (d, 2H), 6.04 (ddt, J = 17.2, 10.2, 5.2 Hz, 1H), 5.41 (s, 2H), 5.18 (dd, J = 10.2, 1.6 Hz, 1H), 5.04 (dd, J = 17.2, 1.6 Hz, 1H), 3.56 (m, 2H). 13 C NMR (151 MHz, CDCl3) δ 137.8, 136.7, 135.6, 135.3, 134.0, 129.4, 128.7, 128.4, 127.2, 127.2, 126.0, 125.8, 121.7, 119.9, 119.2, 116.6, 115.8, 109.4, 46.6, 29.2. IR (film) ν : 3059, 1603, 1465, 1370, 1180, 916, 774, 732, 702 cm -1 HRMS (ESI-TOF) m/z calcd for C24H21N [M + ] 323,1674 Found: 323,1675 2-allyl-1-benzyl-3-(4-methoxyphenyl)-1H-indole 3c This compound was synthesized according to the general procedure starting with 50 mg (0.145 mmol) of 2c and purified using 5-10% ethyl acetate in hexanes; Isolated yield 38 mg (75%); Colorless oil; 1 H NMR (600 MHz, CDCl3) δ 7.69 (d, 1H), 7.50 7.41 (m, 2H), 7.30 7.20 (m, 4H), 7.15 (m, 2H), 7.04 6.97 (m, 4H), 6.00 (ddt, J = 17.1, 10.3, 5.2 Hz, 1H), 5.38 (s, 2H), 5.14 (dd, J = 10.3, 1.6 Hz, 1H), 5.01 (dd, J = 17.1, 1.6 Hz, 1H), 3.87 (s, 3H), 3.51 (dt, J = 5.2, 1.6 Hz, 2H). 13 C NMR (151 MHz, CDCl3) δ 137.9, 136.6, 135.7, 133.6, 130.5, 128.7, 127.7, 127.4, 127.1, 125.9, 121.5, 119.7, 119.1, 116.5, 115.4, 113.9, 109.4, 55.2, 46.6, 29.2. IR (film) ν : 3057, 1507, 1465, 1245, 1177, 1034, 733 cm -1 HRMS (ESI-TOF) m/z calcd for C25H23NO [M + ] 353,1780 Found: 353,1783 ethyl 4-(2-allyl-1-benzyl-1H-indol-3-yl)benzoate 3d This compound was synthesized according to the general procedure starting with 50 mg (0.129 mmol) of 2d and purified using 5% ethyl acetate in hexanes; Isolated yield 43 mg (84%); Yellow solid, m.p. 80-82 o C; 1 H NMR (500 MHz, CDCl3) δ 8.12 (d, 2H), 7.73 (d, 1H), 7.61 (d, 2H), 7.32 7.12 (m, 6H), 6.98 (d, 2H), 6.00 (ddd, J = 17.2, 10.2, 5.1 Hz, 1H), 5.38 (s, 2H), 5.16 (dd, J = 10.2, 1.4 Hz, 1H), 5.00 (dd, J = 17.2, 1.4 Hz, 1H), 4.40 (q, J = 7.1 Hz, 2H), 3.53 (m, 1H), 1.41 (t, J = 7.1 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 166.7, 140.3, 137.5, 136.8, 135.1, 134.7, 129.7, 129.0, 128.8, 127.8, 127.3, 126.8, 125.8, 122.0, 120.3, 119.0, 116.9, 115.0, 109.7, 60.8, 46.7, 29.2, 14.3. IR (film) ν : 3060, 1712, 1607, 1273, 1103, 1021, 734 cm -1 HRMS (ESI-TOF) m/z calcd for C27H26NO2 [M+H + ] 396,1964 Found: 396,1964 4-(2-allyl-1-benzyl-1H-indol-3-yl)benzonitrile 3e This compound was synthesized according to the general procedure starting with 50 mg (0.147 mmol) of 2e and purified using 10% ethyl acetate in hexanes; Isolated yield 38 mg (75%); Colorless oil; 1 H NMR (500 MHz, CDCl3) δ 7.77 7.69 (m, 3H), 7.68 7.62 (m, 2H), 7.35 7.15 (m, 6H), 6.99 (d, 2H), 6.02 (ddd, J = 17.2, 10.2, 5.1 Hz, 1H), 5.39 (s, 2H), 5.20 (dd, J = 10.2, 1.4 Hz, 1H), 4.99 (dd, J = 17.2, 1.4 Hz, 1H), 3.52 (m, 2H). 13 C NMR (126 MHz, CDCl3) δ 140.5, 137.3, 136.9, 135.0, 134.8, 132.3, 129.6, 128.8, 127.4, 126.5, 125.8, 122.3, 120.6, 119.3, 118.7, 117.2, 114.3, 109.8, 109.1, 46.7, 29.1. IR (film) ν : 3060, 2224, 1604, 1465, 1370, 1177, 842, 749, 734 cm -1 HRMS (ESI-TOF) m/z calcd for C25H20N2Na [M+Na + ] 371,1524 Found: 371,1524 2-allyl-1-benzyl-3-(2-nitrophenyl)-1H-indole 3f This compound was synthesized according to the general procedure starting with 50 mg (0.139 mmol) of 2f and purified using 5% ethyl acetate in hexanes; Isolated yield 33
mg (65%); Orange oil; 1 H NMR (500 MHz, CDCl3) δ 7.98 (d, 1H), 7.64 (m, 1H), 7.57 7.48 (m, 2H), 7.36 7.20 (m, 5H), 7.17 (t, 1H), 7.10 (m, 1H), 6.98 (d, 2H), 5.86 (ddd, J = 17.2, 10.2, 5.5 Hz, 1H), 5.42 (AB, 2H), 5.07 (dd, J = 10.2, 1.5 Hz, 1H), 4.98 (dd, J = 17.2, 1.5 Hz, 1H), 3.40 (m, 2H). 13 C NMR (126 MHz, CDCl3) δ 150.6, 137.5, 136.6, 135.0, 134.6, 133.8, 132.1, 129.8, 128.8, 127.7, 127.3, 127.2, 125.7, 124.3, 122.0, 120.2, 118.3, 116.7, 110.9, 109.6, 46.7, 29.4. IR (film) ν : 3060, 1612, 1524, 1353, 850, 744, 732 cm -1 HRMS (ESI-TOF) m/z calcd for C24H21N2O2 [M+H + ] 369,1603 Found: 369,1606 3.2. Indoles 4a-f. To a suspension of Schwartz s reagent (1 equiv.) in THF (1 ml) cooled to -20 o C was added oxindole (50 mg). The reaction mixture was stirred at RT until it cleared. It was cooled to -20 o C and TFA (2 equiv.) and acetophenone enol TMS ether (3 equiv.) were added. The reaction mixture was stirred until TLC showed the reaction to be complete. The reaction was quenched with saturated NaHCO3 and ether (5 ml) was added. The aqueous layer was extracted twice with ether (2x5 ml) and the combined extracts washed with brine. They were dried with Na2SO4 and evaporated. The crude was dissolved in CH2Cl2 (5 ml) and TFA (2 equiv.) was added at RT. When the dehydration was complete (TLC control), ethyl acetate (5 ml) was added and the reaction mixture evaporated under reduced pressure. The product was purified by FCC in the appropriate solvent system. 2-(1-benzyl-3-methyl-1H-indol-2-yl)-1-phenylethanone 4a This compound was synthesized according to the general procedure starting with 50 mg (0.198 mmol) of 2a and purified using 10% ethyl acetate in hexanes; Isolated yield 55 mg (82%); White solid, m.p. 152-155 o C; 1 H NMR (600 MHz, CDCl3) δ 7.92 (m, 2H), 7.57 (t, 2H), 7.44 (t, 2H), 7.24 7.17 (m, 4H), 7.18 7.09 (m, 2H), 6.91 (m, 2H), 5.32 (s, 2H), 4.34 (s, 2H), 2.32 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 196.1, 138.0, 137.0, 136.4, 133.3, 129.2, 128.6, 128.6, 128.3, 127.1, 126.0, 121.6, 118.9, 118.5, 109.7, 109.2, 46.9, 35.4, 9.1. IR (film) ν : 3057, 1689, 1467, 1450, 1212, 739, 690 cm -1 HRMS (ESI-TOF) m/z calcd for C24H22NO [M+H + ] 340,1701 Found: 340,1706 2-(1-benzyl-3-phenyl-1H-indol-2-yl)-1-phenylethanone 4b This compound was synthesized according to the general procedure starting with 50 mg (0.159 mmol) of 2b and purified using 7.5% ethyl acetate in hexanes; Isolated yield 52 mg (82%); Yellow solid, m.p. 59-62 o C; 1 H NMR (500 MHz, CDCl3) δ 7.82 (d, 2H), 7.72 (d, 1H), 7.55 (t, 1H), 7.51 7.35 (m, 6H), 7.35 7.12 (m, 7H), 6.98 (m, 2H), 5.39 (s, 2H), 4.45 (s, 2H). 13 C NMR (126 MHz, CDCl3) δ 196.4, 137.5, 137.0, 135.9, 135.0, 133.4, 129.9, 129.6, 128.7, 128.6, 128.5, 128.5, 128.3, 128.2, 127.3, 127.1, 126.3, 126.0, 122.1, 119.9, 119.2, 117.4, 109.6, 47.2, 35.9. IR (film) ν : 3058, 1687, 1465, 1217, 737, 704 cm -1 HRMS (ESI-TOF) m/z calcd for C29H23NONa [M+Na + ] 424,1677 Found: 424,1674 2-(1-benzyl-3-(4-methoxyphenyl)-1H-indol-2-yl)-1-phenylethanone 4c This compound was synthesized according to the general procedure starting with 50 mg (0.145 mmol) of 2c and purified using 5% ethyl acetate in hexanes; Isolated yield 49 mg (78%); Off-white solid, m.p. 142-143 o C; 1 H
NMR (600 MHz, CDCl3) δ 7.81 (d, 2H), 7.66 (d, 1H), 7.54 (t, 1H), 7.42 7.34 (m, 4H), 7.29 7.16 (m, 5H), 7.13 (t, 1H), 6.97 (m, 4H), 5.37 (s, 2H), 4.41 (s, 2H), 3.85 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 196.5, 158.3, 137.6, 137.0, 136.0, 133.4, 130.8, 129.7, 128.7, 128.5, 128.4, 127.3, 127.3, 127.3, 126.1, 122.0, 119.8, 119.2, 117.0, 114.1, 109.5, 55.3, 47.2, 36.0. IR (film) ν : 3058, 1687, 1508, 1465, 1246, 1217, 1031, 736, 690 cm -1 HRMS (ESI-TOF) m/z calcd for C30H26NO2 [M+H + ] 432,1964 Found: 432,1966 ethyl 4-(1-benzyl-2-(2-oxo-2-phenylethyl)-1H-indol-3-yl)benzoate 4d This compound was synthesized according to the general procedure starting with 50 mg (0.129 mmol) of 2d and purified using 15% ethyl acetate in hexanes; Isolated yield 35 mg (57%); Yellow solid, m.p. 59-61 o C; 1 H NMR (500 MHz, CDCl3) δ 8.10 (d, 2H), 7.84 (d, 2H), 7.71 (d, 1H), 7.57 (t, 1H), 7.53 (d, 1H), 7.41 (t, 2H), 7.30 (d, 1H), 7.28 7.20 (m, 5H), 7.17 (t, 1H), 6.98 (m, 2H), 5.37 (s, 2H), 4.45 (s, 2H), 4.40 (q, J = 7.1 Hz, 2H), 1.41 (t, J = 7.1 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 196.1, 166.6, 140.0, 137.2, 137.2, 135.8, 133.6, 130.6, 129.9, 129.3, 128.8, 128.7, 128.3, 128.2, 127.4, 126.7, 126.0, 122.4, 120.4, 119.1, 116.6, 109.8, 60.8, 47.3, 35.9, 14.3. IR (film) ν : 3059, 1711, 1688, 1606, 1273, 1103, 739 cm -1 HRMS (ESI-TOF) m/z calcd for C32H28NO3 [M+H + ] 474,2069 Found: 474,2076 4-(1-benzyl-2-(2-oxo-2-phenylethyl)-1H-indol-3-yl)benzonitrile 4e This compound was synthesized according to the general procedure starting with 50 mg (0.147 mmol) of 2e and purified using 15% ethyl acetate in hexanes; Isolated yield 46 mg (73%); Yellow oil; 1 H NMR (500 MHz, CDCl3) δ 7.86 (d, 2H), 7.69 (d, 2H), 7.61 (t, 1H), 7.56 (d, 2H), 7.45 (t, 2H), 7.33 (d, 1H), 7.25 (m, 4H), 7.20 (m, 1H), 6.97 (m, 2H), 5.36 (s, 2H), 4.43 (s, 2H). 13 C NMR (126 MHz, CDCl3) δ 195.8, 140.2, 137.2, 137.0, 135.7, 133.8, 132.4, 131.0, 129.9, 128.8, 128.8, 128.2, 127.5, 126.4, 126.0, 122.7, 120.7, 119.1, 118.7, 116.0, 109.9, 109.6, 47.3, 35.7. IR (film) ν : 3060, 2224, 1687, 1604, 1465, 1218, 847, 735, 690 cm -1 HRMS (ESI-TOF) m/z calcd for C30H22N2ONa [M+Na + ] 449,1630 Found: 449,1628 2-(1-benzyl-3-(2-nitrophenyl)-1H-indol-2-yl)-1-phenylethanone 4f This compound was synthesized according to the general procedure starting with 50 mg (0.139 mmol) of 2f and purified using 15% ethyl acetate in hexanes; Isolated yield 42 mg (67%); Green oil; 1 H NMR (500 MHz, CDCl3) δ 7.95 (d, 1H), 7.78 (d, 2H), 7.55 (m, 2H), 7.51 7.44 (m, 2H), 7.38 (t, 2H), 7.33 7.21 (m, 7H), 7.18 (t, 1H), 7.09 (t, 1H), 6.95 (d, 2H), 5.38 (AB, 2H), 4.31 (s, 2H). 13 C NMR (126 MHz, CDCl3) δ 195.6, 150.5, 137.1, 136.9, 135.9, 134.0, 133.5, 132.3, 131.1, 129.3, 128.8, 128.6, 128.2, 128.0, 127.4, 127.2, 125.9, 124.2, 122.4, 120.3, 118.4, 112.4, 109.8, 47.3, 35.8. IR (film) ν : 3060, 1687, 1524, 1353, 1218, 738, 690 cm -1 HRMS (ESI-TOF) m/z calcd for C29H23N2O3 [M+H + ] 447,1709 Found: 447,1708 3.3. Indoles 5a-f. To a suspension of Schwartz s reagent (1 equiv.) in THF (1 ml) cooled to -20 o C was added oxindole (50 mg). The reaction mixture was stirred at RT until it cleared. It was cooled to -20 o C
and TFA (2 equiv.) and indole (3 equiv.) were added. The reaction mixture was stirred until TLC showed the reaction to be complete. The reaction was quenched with saturated NaHCO3 and ether (5 ml) was added. The aqueous layer was extracted twice with ether (2x5 ml) and the combined extracts washed with brine. They were dried with Na2SO4 and evaporated. The crude was dissolved in CH2Cl2 (5 ml) and TFA (2 equiv.) was added at RT. When the dehydration was complete (TLC control), ethyl acetate (5 ml) was added and the reaction mixture evaporated under reduced pressure. The product was purified by FCC in the appropriate solvent system. 1-benzyl-3-methyl-1H,1'H-2,3'-biindole 5a This compound was synthesized according to the general procedure starting with 50 mg (0.198 mmol) of 2a and purified using 15% ethyl acetate in hexanes; Isolated yield 53 mg (80%); Clear oil; 1 H NMR (600 MHz, CDCl3) δ 8.16 (br s, 1H), 7.72 7.62 (m, 1H), 7.46 (d, 1H), 7.39 (d, 1H), 7.30 7.10 (m, 8H), 7.01 (d, 1H), 6.91 (d, 2H), 5.24 (br s, 2H), 2.30 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 139.0, 136.8, 135.7, 131.1, 129.0, 128.4, 127.7, 126.8, 125.9, 124.7, 124.0, 122.4, 121.9, 121.4, 120.6, 120.3, 120.1, 119.7, 119.0, 118.5, 111.2, 110.9, 110.1, 109.9, 107.4, 102.5, 47.3, 9.7. IR (film) ν : 3405, 3055, 1464, 1454, 1355, 742, 699 cm -1 HRMS (ESI-TOF) m/z calcd for C24H20N2 [M + ] 336,1626 Found: 336,1624 1-benzyl-3-phenyl-1H,1'H-2,3'-biindole 5b This compound was synthesized according to the general procedure starting with 50 mg (0.159 mmol) of 2b and purified using 10-15% ethyl acetate in hexanes; Isolated yield 44 mg (70%); Colorless solidifying oil; 1 H NMR (600 MHz, CDCl3) δ 8.08 (br s, 1H), 7.87 (d, 1H), 7.39 (d, 2H), 7.35 7.24 (m, 3H), 7.24 7.12 (m, 8H), 7.10 (t, 1H), 7.01 (t, 1H), 6.97 6.92 (m, 3H), 5.29 (s, 2H). 13 C NMR (151 MHz, CDCl3) δ 138.4, 137.0, 135.7, 135.7, 131.4, 129.3, 128.5, 128.0, 127.7, 127.5, 126.9, 126.1, 125.5, 125.3, 122.4, 121.9, 120.4, 120.1, 120.0, 119.4, 116.6, 111.1, 110.3, 107.2, 47.5. IR (film) ν : 3409, 3056, 1602, 1454, 1095, 773, 742, 700 cm -1 HRMS (ESI-TOF) m/z calcd for C29H22N2 [M + ] 398,1783 Found: 398,1773 1-benzyl-3-(4-methoxyphenyl)-1H,1'H-2,3'-biindole 5c This compound was synthesized according to the general procedure starting with 50 mg (0.145 mmol) of 2c and purified using 20% ethyl acetate in hexanes; Isolated yield 45 mg (73%); Colorless solid, m.p. 168-169 o C; 1 H NMR (500 MHz, CDCl3) δ 8.13 (br s, 1H), 7.83 (d, 1H), 7.32 (m, 4H), 7.26 m, 2H), 7.22 7.12 (m, 6H), 7.02 (t, 1H), 6.95 (m, 3H), 6.75 (d, 2H), 5.28 (s, 2H), 3.73 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 157.4, 138.5, 136.9, 135.7, 130.9, 130.3, 128.4, 128.1, 127.8, 127.6, 126.9, 126.1, 125.5, 122.4, 121.8, 120.4, 120.0, 119.9, 119.4, 116.2, 113.5, 111.1, 110.3, 107.3, 55.1, 47.5. IR (film) ν : 3408, 3053, 1606, 1528,
1462, 1244, 1177, 1032, 742, 700 cm -1 HRMS (ESI-TOF) m/z calcd for C30H24N2ONa [M+Na + ] 451,1786 Found: 451,1776 ethyl 4-(1-benzyl-1H,1'H-[2,3'-biindol]-3-yl)benzoate 5d This compound was synthesized according to the general procedure starting with 50 mg (0.129 mmol) of 2d and purified using 25% ethyl acetate in hexanes; Isolated yield 42 mg (69%); Colorless oil; 1 H NMR (500 MHz, CDCl3) δ 8.23 (br s, 1H), 7.83 (d, 3H), 7.41 (d, 2H), 7.34 (d, 1H), 7.29 7.07 (m, 9H), 7.05 6.86 (m, 4H), 5.27 (br s, 2H), 4.27 (q, J = 7.1 Hz, 2H), 1.30 (t, J = 7.1 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 166.8, 140.8, 138.2, 137.1, 135.8, 132.3, 129.4, 128.8, 128.5, 127.4, 127.0, 126.9, 126.0, 125.5, 122.6, 122.2, 120.6, 120.5, 119.8, 119.2, 115.7, 111.3, 110.5, 106.8, 60.6, 47.5, 14.3. IR (film) ν : 3405, 3056, 1707, 1605, 1461, 1257, 1103, 742, 710 cm -1 HRMS (ESI-TOF) m/z calcd for C32H26N2O2 [M + ] 470,1994 Found: 470,1996 4-(1-benzyl-1H,1'H-[2,3'-biindol]-3-yl)benzonitrile 5e This compound was synthesized according to the general procedure starting with 50 mg (0.147 mmol) of 2e and purified using 25% ethyl acetate in hexanes; Isolated yield 31 mg (49%); White wax; 1 H NMR (500 MHz, CDCl3) δ 8.46 (br s, 1H), 7.99 (m, 1H), 7.57 (m, 4H), 7.48 7.41 (m, 1H), 7.41 7.27 (m, 7H), 7.15 (m, 2H), 7.08 (d, 2H), 5.44 (br s, 2H). 13 C NMR (126 MHz, CDCl3) δ 141.1, 138.0, 137.2, 135.8, 134.1, 132.7, 131.9, 129.3, 128.6, 127.1, 126.7, 126.0, 125.4, 122.8, 122.5, 122.3, 120.8, 120.7, 119.7, 119.6, 119.5, 118.9, 116.2, 114.8, 111.4, 110.7, 108.1, 106.4, 47.5. IR (film) ν : 3403, 3055, 2224, 1603, 1523, 1455, 1092, 852, 743, 698 cm -1 HRMS (ESI-TOF) m/z calcd for C30H21N3Na [M+Na + ] 446,1633 Found: 446,1631 1-benzyl-3-(2-nitrophenyl)-1H,1'H-2,3'-biindole 5f This compound was synthesized according to the general procedure starting with 50 mg (0.139 mmol) of 2f and purified using 25% ethyl acetate in hexanes; Isolated yield 30 mg (49%); Yellow oil; 1 H NMR (500 MHz, CDCl3) δ 8.23 (br s, 1H), 7.71 (d, 1H), 7.50 (m, 2H), 7.43 (m, 1H), 7.39 7.31 (m, 2H), 7.31 7.13 (m, 8H), 7.04 6.93 (m, 4H), 5.36 (s, 2H). 13 C NMR (126 MHz, CDCl3) δ 138.2, 136.9, 135.6, 133.4, 132.5, 132.0, 130.6, 128.6, 127.4, 127.3, 127.1, 127.0, 126.8, 125.9, 124.2, 122.5, 122.2, 120.5, 119.6, 118.3, 111.8, 111.1, 110.6, 47.6. IR (film) ν : 3414, 3058, 1608, 1523, 1456, 1353, 743, 712 cm -1 HRMS (ESI-TOF) m/z calcd for C29H21N3O2Na [M+Na + ] 466,1531 Found: 466,1533 3.4. Indoles 6a-f.
To a suspension of Schwartz s reagent (1 equiv.) in THF (1 ml) cooled to -20 o C was added oxindole (50 mg). The reaction mixture was stirred at RT until it cleared. It was cooled to -20 o C and TFA (2 equiv.) and thiophenol (1 equiv.) were added. The reaction mixture was stirred until TLC showed the reaction to be complete. The reaction was quenched with saturated NaHCO3 and ether (5 ml) was added. The aqueous layer was extracted twice with ether (2x5 ml) and the combined extracts washed with brine. They were dried with Na2SO4 and evaporated. The crude was dissolved in CH2Cl2 (5 ml) and TFA (2 equiv.) was added at RT. When the dehydration was complete (TLC control), ethyl acetate (5 ml) was added and the reaction mixture evaporated under reduced pressure. The product was purified by FCC in the appropriate solvent system. 1-benzyl-3-methyl-2-(phenylthio)-1H-indole 6a This compound was synthesized according to the general procedure starting with 50 mg (0.198 mmol) of 2a and purified using 1-2% ethyl acetate in hexanes; Isolated yield 32 mg (49%); Yellow wax; 1 H NMR (600 MHz, CDCl3) δ 7.72 (d, 1H), 7.32 7.25 (m, 2H), 7.25 7.17 (m, 6H), 7.15 7.10 (m, 1H), 7.06 6.98 (m, 4H), 5.45 (s, 2H), 2.54 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 137.9, 137.7, 137.0, 128.9, 128.4, 127.7, 127.0, 126.4, 126.0, 125.4, 124.1, 123.4, 120.4, 119.5, 119.4, 110.4, 47.1, 10.0. IR (film) ν : 3057, 1581, 1477, 1452, 1357, 1329, 1184, 1023, 739, 696 cm -1 HRMS (ESI-TOF) m/z calcd for C22H19NS [M + ] 329,1238 Found: 329,1234 1-benzyl-3-phenyl-2-(phenylthio)-1H-indole 6b This compound was synthesized according to the general procedure starting with 50 mg (0.159 mmol) of 2b and purified using 1.5% ethyl acetate in hexanes; Isolated yield 52 mg (84%); Off-white solid, m.p. 84-85 o C decomp.; 1 H NMR (600 MHz, CDCl3) δ 7.88 7.84 (d, 1H), 7.70 7.65 (d, 2H), 7.51 7.46 (t, 2H), 7.40 7.15 (m, 9H), 7.15 7.09 (m, 1H), 7.09 7.06 (m, 2H), 7.04 6.99 (m, 2H), 5.50 (s, 2H). 13 C NMR (151 MHz, CDCl3) δ 137.9, 137.5, 137.3, 134.1, 129.9, 129.0, 128.8, 128.7, 128.5, 128.2, 127.3, 127.1, 126.8, 126.8, 126.7, 126.5, 126.0, 125.8, 125.5, 123.9, 123.8, 120.4, 110.7, 47.3. IR (film) ν : 3059, 1603, 1476, 1449, 1330, 739, 698 cm -1 HRMS (ESI-TOF) m/z calcd for C27H21NS [M + ] 391,1395 Found: 391,1393 1-benzyl-3-(4-methoxyphenyl)-2-(phenylthio)-1H-indole 6c This compound was synthesized according to the general procedure starting with 50 mg (0.145 mmol) of 2c and purified using 5% ethyl acetate in hexanes; Isolated yield 41 mg (67%); Colorless solidifying oil; 1 H NMR (500 MHz, CDCl3) δ 7.81 (d, 1H), 7.59 7.52 (d, 2H), 7.34 7.25 (m, 3H), 7.24 7.12 (m, 5H), 7.12 7.02 (m, 3H), 6.98 (m, 4H), 5.46 (s, 2H), 3.86 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 158.5, 137.8, 137.6, 137.5, 130.9, 129.0, 128.5, 127.1, 126.9, 126.5, 126.5, 125.9, 125.5, 125.5, 123.8, 123.5, 120.4, 120.3, 113.8, 110.6, 55.2, 47.3. IR (film) ν : 3058, 1536, 1494, 1450, 1246, 1177, 1031, 740, 693 cm -1 HRMS (ESI-TOF) m/z calcd for C28H23NOSNa [M+Na + ] 444,1398 Found: 444,1397
ethyl 4-(1-benzyl-2-(phenylthio)-1H-indol-3-yl)benzoate 6d This compound was synthesized according to the general procedure starting with 50 mg (0.129 mmol) of 2d and purified using 5% ethyl acetate in hexanes; Isolated yield 25 mg (41%); Off-white solid, m.p. 184-186 o C; 1 H NMR (500 MHz, CDCl3) δ 8.10 (d, 2H), 7.80 (d, 1H), 7.70 (d, 2H), 7.36 7.23 (m, 3H), 7.23 7.10 (m, 5H), 7.07 (t, 1H), 7.05 7.00 (m, 2H), 6.94 (d, 2H), 5.47 (s, 2H), 4.38 (q, J = 7.1 Hz, 2H), 1.39 (t, J = 7.1 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 166.6, 139.0, 137.9, 137.3, 136.8, 129.7, 129.5, 129.1, 128.6, 128.5, 127.3, 126.5, 126.1, 125.8, 124.7, 124.6, 124.1, 120.8, 120.2, 110.9, 60.8, 47.4, 14.3. IR (film) ν : 3059, 1713, 1607, 1450, 1273, 1102, 740, 706 cm -1 HRMS (ESI-TOF) m/z calcd for C30H25NO2SNa [M+Na + ] 486,1504 Found: 486,1504 4-(1-benzyl-2-(phenylthio)-1H-indol-3-yl)benzonitrile 6e This compound was synthesized according to the general procedure starting with 50 mg (0.147 mmol) of 2e and purified using 10% ethyl acetate in hexanes; Isolated yield 41 mg (67%); Orange solidifying oil; 1 H NMR (500 MHz, CDCl3) δ 7.74 (m, 5H), 7.41 7.28 (m, 2H), 7.28 7.13 (m, 6H), 7.10 (t, 1H), 7.07 7.00 (m, 2H), 6.98 6.88 (m, 2H), 5.48 (s, 2H). 13 C NMR (126 MHz, CDCl3) δ 139.2, 137.9, 137.0, 136.4, 132.9, 130.3, 129.2, 128.6, 127.4, 126.4, 126.1, 126.0, 125.9, 125.1, 124.3, 123.6, 121.2, 119.8, 119.2, 111.0, 110.0, 47.5. IR (film) ν : 3059, 2225, 1605, 1450, 1331, 1174, 742, 695 cm -1 HRMS (ESI-TOF) m/z calcd for C28H20N2SNa [M+Na + ] 439,1245 Found: 439,1244 1-benzyl-3-(2-nitrophenyl)-2-(phenylthio)-1H-indole 6f This compound was synthesized according to the general procedure starting with 50 mg (0.139 mmol) of 2f and purified using 10% ethyl acetate in hexanes; Isolated yield 7 mg (12%); Orange waxy solid, no sharp m.p.; 1 H NMR (500 MHz, CDCl3) δ 8.02 (d, 1H), 7.61 (m, 1H), 7.57 7.45 (m, 2H), 7.39 (d, 1H), 7.30 7.16 (m, 6H), 7.12 (m, 3H), 7.08 7.03 (m, 1H), 7.03 6.94 (m, 3H), 5.46 (AB, 2H). 13 C NMR (126 MHz, CDCl3) δ 137.6, 137.2, 136.1, 134.0, 132.3, 129.1, 129.0, 128.6, 128.1, 127.2, 126.7, 126.6, 126.3, 125.9, 124.6, 124.0, 121.2, 120.9, 119.2, 110.9, 47.5. IR (film) ν : 3455, 3060, 1610, 1525, 1451, 1352, 1182, 742, 703 cm -1 HRMS (ESI-TOF) m/z calcd for C27H20N2O2SNa [M+Na + ] 459,1143 Found: 459,1142 3.5. Indoles 7a-d. To a suspension of Schwartz s reagent (1 equiv.) in THF (1 ml) cooled to -20 o C was added oxindole (50 mg). The reaction mixture was stirred at RT until it cleared. It was cooled to -20 o C and TFA (2 equiv.), dimethyl malonate (3 equiv.) and TMSOTf (3 equiv.) were added. The
reaction mixture was stirred until TLC showed the reaction to be complete. The reaction was quenched with saturated NaHCO3 and ether (5 ml) was added. The aqueous layer was extracted twice with ether (2x5 ml) and the combined extracts washed with brine. They were dried with Na2SO4 and evaporated. The crude was dissolved in CH2Cl2 (5 ml) and TFA (2 equiv.) was added at RT. When the dehydration was complete (TLC control), ethyl acetate (5 ml) was added and the reaction mixture evaporated under reduced pressure. The product was purified by FCC in the appropriate solvent system. dimethyl 2-(1-benzyl-3-methyl-1H-indol-2-yl)malonate 7a This compound was synthesized according to the general procedure starting with 50 mg (0.198 mmol) of 2a and purified using 10-15% ethyl acetate in hexanes; Isolated yield 35 mg (51%); Clear oil; 1 H NMR (500 MHz, CDCl3) δ 7.71 (d, 1H), 7.41 (m, 1H), 7.38 7.21 (m, 5H), 7.02 (d, 2H), 5.56 (s, 2H), 5.12 (s, 1H), 3.64 (s, 6H), 2.46 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 167.4, 137.5, 137.0, 135.9, 130.6, 128.7, 128.4, 128.0, 127.7, 127.5, 127.2, 127.0, 126.7, 125.8, 123.5, 122.5, 122.3, 119.3, 119.0, 111.6, 109.8, 108.9, 52.7, 49.1, 47.3, 43.6, 40.5. IR (film) ν : 3058, 1739, 1713, 1613, 1467, 1029, 740, 698 cm -1 HRMS (ESI-TOF) m/z calcd for C21H21NO4Na [M+Na + ] 374.1368 Found: 374.1367 dimethyl 2-(1-benzyl-3-phenyl-1H-indol-2-yl)malonate 7b This compound was synthesized according to the general procedure starting with 50 mg (0.159 mmol) of 2b and purified using 15% ethyl acetate in hexanes; Isolated yield 36 mg (55%); Clear oil; 1 H NMR (500 MHz, CDCl3) δ 7.66 (d, 1H), 7.56 (d, 2H), 7.50 (t, 2H), 7.39 (t, 1H), 7.27 (m, 2H), 7.24 7.12 (m, 4H), 6.97 (d, 2H), 5.59 (s, 2H), 5.27 (s, 1H), 3.43 (s, 6H). 13 C NMR (126 MHz, CDCl3) δ 167.5, 137.2, 137.1, 134.1, 130.2, 128.6, 128.4, 127.2, 127.0, 127.0, 126.8, 125.9, 123.0, 120.2, 119.8, 119.0, 110.4, 52.7, 49.5, 48.1. IR (film) ν : 3059, 1739, 1604, 1452, 1154, 1031, 737, 703 cm -1 HRMS (ESI-TOF) m/z calcd for C26H23NO4Na [M+Na + ] 436.1525 Found: 436.1516 dimethyl 2-(1-benzyl-3-(4-methoxyphenyl)-1H-indol-2-yl)malonate 7c This compound was synthesized according to the general procedure starting with 50 mg (0.145 mmol) of 2c and purified using 15% ethyl acetate in hexanes; Isolated yield 23 mg (35%); Clear oil; 1 H NMR (500 MHz, C6D6) δ 8.18 (d, 1H), 7.99 (d, 2H), 7.57 7.43 (m, 5H), 7.41 7.34 (m, 2H), 7.30 7.23 (m, 2H), 7.16 (m, 2H), 5.95 (s, 2H), 5.91 (s, 1H), 3.36 (s, 6H). 13 C NMR (126 MHz, C6D6) δ 167.8, 159.4, 137.9, 137.9, 131.9, 129.9, 126.9, 126.2, 125.4, 123.4, 122.5, 120.7, 120.4, 119.3, 114.7, 114.6, 110.6, 109.0, 54.8, 54.7, 52.3, 51.3, 50.2, 48.5, 43.7, 31.5, 30.4, 30.2. IR (film) ν : 3059, 2952, 1738, 1715, 1610, 1509, 1248, 1033, 735, 697 cm -1 HRMS (ESI-TOF) m/z calcd for C27H25NO5Na [M+Na + ] 466.1630 Found: 466.1633
dimethyl 2-(1-benzyl-3-(4-(ethoxycarbonyl)phenyl)-1H-indol-2- yl)malonate 7d This compound was synthesized according to the general procedure starting with 50 mg (0.129 mmol) of 2d and purified using 15% ethyl acetate in hexanes; Isolated yield 37 mg (59%); Clear oil; 1 H NMR (500 MHz, C6D6) δ 8.27 (d, 2H), 7.74 7.65 (m, 3H), 7.12 (m, 2H), 6.97 (d, 1H), 6.89 (m, 3H), 6.80 6.73 (m, 2H), 5.54 (s, 2H), 5.43 (s, 1H), 4.16 (q, J = 7.1 Hz, 2H), 2.97 (s, 6H), 1.05 (t, J = 7.1 Hz, 3H). 13 C NMR (126 MHz, C6D6) δ 167.5, 166.2, 139.5, 137.9, 137.5, 130.5, 130.5, 129.6, 126.2, 123.7, 121.2, 120.1, 118.6, 111.1, 60.7, 52.3, 50.1, 48.5, 14.3. IR (film) ν : 2955, 2925, 1739, 1715, 1607, 1274, 741, 710 cm -1 HRMS (ESI-TOF) m/z calcd for C29H27NO6Na [M+Na + ] 508.1736 Found: 508.1740 4. Experimental details and characterization data of tetrahydroquinoline 8 To a suspension of Schwartz s reagent (1 equiv.) in THF (1 ml) cooled to - 20 o C was added oxindole 2a (50 mg, 0.198 mmol). The reaction mixture was stirred at RT until it cleared. It was cooled to -20 o C and TFA (2 equiv.) and TMSCN (3 equiv.) were added. The reaction mixture was stirred until TLC showed the reaction to be complete. The reaction was quenched with saturated NaHCO3 and ether (5 ml) was added. The aqueous layer was extracted twice with ether (2x5 ml) and the combined extracts washed with brine. They were dried with Na2SO4 and evaporated under reduced pressure. The product was purified by FCC with 10% ethyl acetate in hexanes as the eluent. rac-1-((3ar,4r,9bs)-5-benzyl-3a,4,5,9b-tetrahydro-3h-cyclopenta[c]quinolin-4-yl)ethanone 8 Isolated yield 34 mg (56%); Yellow oil; 1 H NMR (600 MHz, CDCl3) δ 7.34 7.28 (m, 3H), 7.28 7.22 (m, 2H), 7.01 6.95 (m, 2H), 6.68 (t, 1H), 6.63 (d, 1H), 5.85 5.67 (m, 2H), 4.78 4.13 (AB, 2H), 3.86 (d, 1H), 3.72 (d, 1H), 3.23 (m, 1H), 2.64 2.53 (m, 2H), 2.04 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ 210.3, 144.2, 138.1, 134.9, 129.4, 128.7, 128.6, 127.4, 127.2, 126.9, 126.2, 118.2, 112.9, 70.7, 55.5, 43.7, 40.0, 37.3, 27.7. IR (film) ν : 3059, 2925, 1710, 1495, 1352, 1181, 745, 699 cm -1 HRMS (ESI-TOF) m/z calcd for C21H21NONa [M+Na + ] 326.1521 Found: 326.1511
5. Copies of 1 H- and 13 C-NMR spectra for compounds 2a-8
Encircled in red are the peaks confirming the tetrahydroquinoline structure.
6. References 1 C. Piemontesi, Q. Wang and J. Zhu, Org. Biomol. Chem., 2013, 11, 1533 1536. 2 A. Takamizawa and H. Harada, Chem. Pharm. Bull. (Tokyo), 1980, 28, 769 778.