Supporting Information for. Visible Light Mediated Intermolecular C H Functionalization of Electron Rich Heterocycles with Malonates

Transcription

1 Supporting Information for Visible Light Mediated Intermolecular C H Functionalization of Electron Rich Heterocycles with Malonates Laura Furst, Bryan S. Matsuura, Jagan M.R. Narayanam, Joseph W. Tucker, and Corey R.J. Stephenson Table of Contents: 1. General Information/Reaction Apparatus... S2 2. Experimental procedures for photoredox catalyzed reactions... S3 3. Data for compounds afforded by photoredox reactions... S4-S18 4. Luminescence Quenching Procedure/Data... S19 5. References... S H and 13 C NMR Spectra for all new compounds... S21-S51 S1

2 General Information Chemicals were either used as received or purified according to Purification of Common Laboratory Chemicals [1]. Glassware was dried in an oven at 150 C or flame dried and cooled under a dry atmosphere prior to use. All reactions were performed using common dry, inert atmosphere techniques. Reactions were monitored by TLC and visualized by a dual short wave/long wave UV lamp and stained with an ethanolic solution of potassium permanganate or p-anisaldehyde. Column flash chromatography was performed using mesh silica gel. NMR spectra were recorded on Varian Mercury 300, Varian Unity Plus 400, and Varian Mercury 400 spectrometers. Chemical shifts for 1 H NMR were reported as δ, parts per million, relative to the signal of CHCl 3 at 7.26 ppm. Chemical shifts for 13 C NMR were reported as δ, parts per million, relative to the center line signal of the CDCl 3 triplet at 77.0 ppm. Proton and carbon assignments were established using spectral data of similar compounds. The abbreviations s, br. s, d, dd, br. d, ddd, t, q, br. q, m, and br. m stand for the resonance multiplicity singlet, broad singlet, doublet, doublet of doublets, broad doublet, doublet of doublet of doublets, triplet, quartet, broad quartet, multiplet and broad multiplet, respectively. IR spectra were recorded on an Avatar 360 FT-IR spectrometer. Mass spectra were recorded at the Mass Spectrometry Facility at the Department of Chemistry of the Boston University in Boston, MA on a Waters Q-Tof API-US with ESI high resolution mass spectrometer. Concentration refers to removal of solvent under reduced pressure (house vacuum at ca. 20 mm Hg) Reaction Apparatus S2

3 Byproducts from Visible Light Mediated Malonyl Radical Cyclization Dimethyl 2,3-dihydro-1H-pyrrolo[1,2-a]indole-1,1-dicarboxylate (B) 1 and dimethyl 2-(2- (1H-indol-1-yl)ethyl)-2-(2-oxoethyl)malonate (C) (Figure 2). A flame dried 10 ml round bottom flask was equipped with a rubber septum and magnetic stir bar and was charged with tris(2,2 -bipyridyl)ruthenium(ii) chloride hexahydrate (1.6 mg, 2.1 mol, equiv), A (75 mg, 0.21 mmol, 1.0 equiv), Et 3 N (58 L, 0.42 mmol, 2.0 equiv) and DMF (4.2 ml). The mixture was degassed by the freeze-pump-thaw procedure, and placed at a distance of ~10 cm from a 15 W fluorescent lamp. After the reaction was complete (12 h, as judged by TLC analysis), the mixture was poured into a separatory funnel containing 25 ml of Et 2 O and 25 ml of H 2 O. The layers were separated and the aqueous layer was extracted with Et 2 O (2 X 50 ml). The combined organic layers were dried (Na2SO4) and concentrated. The residue was purified by chromatography on SiO 2 (95:5, hexanes/etoac) to provide B (13 mg, 22%) and C (13 mg, 20%) as colorless solids. Data for B: R f (7:3 Hexanes/EtOAc) 0.39; 1 H NMR (400 MHz): (m, 1 H), (m, 1 H), (m, 1 H), (m, 1 H), 7.55 (d, J = 0.8 Hz, 1 H), 4.21 (t, J = 6.8 Hz, 2 H), 3.80 (s, 6 H), 3.19 (t, J = 6.8 Hz, 2 H). Data for C: Rf (7:3 Hexanes/EtOAc) 0.18; IR (neat): 2955, 1732, 1462, 1352, 1215, 764 cm -1 ; 1 H NMR (300 MHz): 9.64 (s, 1 H), 7.60 (d, J = 7.8 Hz, 1 H), 7.34 (d, J = 7.8 Hz, 1 H), 7.21 (t, J = 7.4 Hz, 1 H), 7.09 (t, J = 7.4 Hz, 1 H), 7.03 (d, J = 3.3 Hz, 1 H), 6.47 (d, J = 3.3 Hz, 1 H), (m, 2 H), 3.72 (s, 6 H), 3.02 (s, 2 H), (m, 2 H); 13 C NMR (75 MHz): δ 198.0, 170.3, 135.6, 128.7, 127.4, 121.5, 119.5, 109.3, 101.7, 53.3, 53.1, 46.9, 42.5, 34.2, 29.7; 1 Magolan, J.; Kerr, M. A. Org. Lett. 2006, 8, S3

4 HRMS (ESI) m/z calculated for C 14 H 19 NaNO 5 + ([M+Na] + ) , found General Procedure for Photoredox Catalyzed Alkylation of Heteroaromatics A flame dried 10 ml round bottom flask was equipped with a rubber septum and magnetic stir bar and was charged with the heteroaromatic compound (0.15 mmol, 1.0 equiv), tris(2,2 bipyridyl)ruthenium(ii) chloride hexahydrate (1.5 µmol, 0.01 equiv), 4-methoxytriphenylamine (0.30 mmol, 2.0 equiv), diethyl bromomalonate (0.30 mmol, 2.0 equiv) and DMF (1.5 ml). The mixture was degassed via the freeze-pump-thaw method and placed at a distance of ~2-5 cm from blue light emitting diodes (LEDs) [2]. After the reaction was complete (as judged by TLC analysis), the mixture was poured into a separatory funnel containing 25 ml of EtOAc and 25 ml of H 2 O. The layers were separated and the aqueous layer was extracted with EtOAc (2 X 50 ml). The combined organic layers were washed with 25 ml of water and 25 ml of brine, dried (Na 2 SO 4 ) and concentrated. The residue was purified by chromatography on silica gel, using the solvent system indicated, to afford the desired alkylated product. Diethyl 2-(1-methyl-1H-indol-2-yl)malonate (Table 1, entry 1). According to the general procedure, N-methylindole (0.10 g, 0.76 mmol), diethyl bromomalonate (0.20 ml, 1.2 mmol), 4- methoxytriphenylamine (0.42 g, 1.6 mmol) and tris(2,2 -bipyridyl)ruthenium(ii) chloride hexahydrate (6.0 mg, 7.6 µmol) afforded the coupled product (0.18 g, 82%) as a yellow-orange oil after purification on SiO 2 (95:5, hexanes/etoac) (18 h reaction time). R f (95:5 Hexanes/EtOAc) = 0.17; IR (neat): 3409, 5979, 2935, 1692, 1508, 1457, 1392, 1366, 1244, 1167, 1028, 741 cm -1 ; 1 H NMR (400 Mhz): 7.78 (d, J = 7.8 Hz, 1 H), (m, 1 H), (m, 1 H), (m,1 H), 6.78 (s, 1 H), 5.12 (s, 1 H), (m, 4 H), 3.91 (s, 3 H), 1.49 (t, J = 7.1 Hz, 6 H); 13 C NMR (100 MHz): δ 167.6, 156.2, 136.4, 136.3, 127.7, 125.9, 122.9, 119.8, 119.2, 122.6, 111.5, 62.7, 62.7, 49.5, 41.3, 28.7, 25.0, 14.3; HRMS (ESI) m/z calculated for C 16 H 19 NO 4 [M+1] , found S4

5 Diethyl 2-(4-bromo-1-methyl-1H-indol-2-yl)malonate (Table 1 Entryl 2). According to the general procedure, 4-bromo-1-methylindole (50 mg, 0.24 mmol), diethyl bromomalonate (0.08 ml, 0.48 mmol), 4-methoxytriphenylamine (0.13 g, 0.48 mmol) and tris(2,2 bipyridyl)ruthenium(ii) chloride hexahydrate (2.0 mg, 2.4 µmol) afforded the coupled product (88 mg, 91%) as an orange oil after purification on SiO 2 (98:2, hexanes/etoac) (4 days reaction time). R f (90:10 Hexanes/EtOAc) = 0.16; IR (neat): 2981, 2928, 1732, 1653, 1537, 1457, 1424, 1368, 1344, 1214, 1150, 1030, 764 cm -1 ; 1 H NMR (400 MHz): δ (m, 1 H), (m,1 H), 6.59 (s, 1 H), 4.89 (s, 1 H), (m, 4 H), 3.64 (s, 3 H), 1.25 (t, J = 7.1 Hz, 6 H); 13 C NMR (100 MHz): δ 166.9, 131.9, 128.2, 123.1, 122.9, 115.0, 108.8, 103.7, 62.6, 51.6, 31.1; HRMS (ESI) m/z calculated for C 16 H 18 BrNO 4 [M+1] , found S5

6 Diethyl 2-(1,3-dimethyl-1H-indol-2-yl)malonate (Table 1, Entry 3). According to the general procedure, 3-methylindole (50 mg, 0.38 mmol), diethyl bromomalonate (91 μl, 0.53 mmol,), 4- methoxytriphenylamine (0.21 g, 0.53 mmol) and tris(2,2 -bipyridyl)ruthenium(ii) chloride hexahydrate (3.0 mg, 3.8 µmol) afforded the coupled product (92 mg, 84%) as a yellow oil after purification on SiO 2 (90:5:5 hexanes/etoac/acoh) (8 h reaction time). R f (93:5:2, Hexanes/EtOAc/AcOH) = 0.50; IR (neat): 3414, 3060, 2982, 2936, 1731, 1621, 1460,1369, 1318, 1243 cm -1 ; 1 H NMR (400 MHz): δ 8.93 (br s, 1 H, NH), 7.55 (dd, J = 7.8, 1.2 Hz, 1 H), (m, 1 H), (m, 1 H), (m, 1 H), (m, 4 H), (m, 3 H), (m, 6 H); 13 C NMR (100 MHz) δ 167.4, 135.8, 128.2, 124.5, 122.4, 119.2, 118.8, 111.1, 110.6, 62.3, 49.3, 49.3, 14.0, 8.5; HRMS (ESI) m/z calculated for C 16 H 19 NO 4 [M+1] , found S6

7 Diethyl 2-(2-(methoxycarbonyl)-1-methyl-1H-indol-3-yl)malonate (Table 1, Entry 4). According to the general procedure, methyl 1-methylindole-2-carboxylate (50 mg mmol), diethyl bromomalonate (90 μl, 0.53 mmol,), 4-methoxytriphenylamine (0.14 g, 0.53 mmol) and tris(2,2 -bipyridyl)ruthenium(ii) chloride hexahydrate (2.0 mg, 2.6 µmol) afforded the coupled product (84 mg, 93%) as a light green solid after purification on SiO 2 (1:9 hexanes/etoac) (24 h reaction time). R f (90:10, Hexanes/EtOAc) = 0.14; IR (neat): 2983, 2956, 2362, 2331, 1732, 1714, 1532, 1468, 1441, 1398, 1368, 1311, 1241, 1150, 1109, 1050, 862, 745 cm -1 ; 1 H NMR (400 MHz): δ (m, 1 H), (m, 2 H), (m, 1 H), 5.75 (s, 1 H), (m, 4 H), 4.02 (s, 3 H), 3.94 (s, 3 H), 1.24 (t, J = 7.1 Hz, 6 H); 13 C NMR (100 MHz): δ 168.8, 162.7, 138.9, 126.4, 125.9, 125.6, 122.2, 121.0, 114.7, 110.6, 61.9, 52.0, 50.2, 32.5, 14.3; HRMS (ESI) m/z calculated for C 18 H 21 NNaO 6 [M+Na] , found S7

8 Diethyl 2-(3-(2-bromoethyl)-1H-indol-2-yl)malonate (Table 1, Entry 5). According to the general procedure, 3-(2-bromoethyl)indole (50 mg, 0.22 mmol), diethyl bromomalonate (75 μl, 0.45 mmol,), 4-methoxytriphenylamine (0.12 g, 0.45 mmol) and tris(2,2 -bipyridyl)ruthenium(ii) chloride hexahydrate (3.0 mg, 2.2 µmol) afforded the coupled product (64 mg, 76%) as a light pink solid after purification on SiO 2 (95:5 hexanes/acetone) (12 h reaction time). R f (90:10 Hexanes/EtOAc) 0.13; IR (neat): 3399, 2982, 1729, 1459, 1310, 1242, 1204, 1151, 1030 cm -1 ; 1 H NMR (400 MHz): δ 9.03 (br s, 1 H, NH), 7.56 (d, J = 8.0 Hz, 1 H), 7.38 (dd, J = 8.1, 0.9 Hz, 1 H), 7.22 (tt, J = 7.6, 1.0 Hz, 1 H), (m, 1 H), 5.00 (s, 1 H), (m, 4 H), (m, 2 H), (m, 2 H), 1.29 (t, J = 6.6 Hz, 6 H); 13 C NMR (100 MHz): δ 167.0, 135.8, 125.9, 122.7, 119.8, 118.4, 112.2, 111.4, 77.2, 62.5, 49.2, 32.3, 28.3, 14.0; HRMS (ESI) m/z calculated for C 17 H 21 BrNO 4 [M+1] , found S8

9 Diethyl 2-(3-(2-((tert-butoxycarbonyl)amino)ethyl)-1H-indol-2-yl)malonate (Table 1, Entry 6; R = H). According to the general procedure, N-Boc-tryptamine (0.50 g, 2.0 mmol), diethyl bromomalonate (0.70 ml, 4.1 mmol), 4-methoxytriphenylamine (1.1 g, 4.1 mmol) and tris(2,2 bipyridyl)ruthenium(ii) chloride hexahydrate (18 mg, 0.02 mmol) afforded The coupled productthe coupled product (0.62 g, 73%) as a white solid after purification on SiO 2 (4:1 hexanes/etoac) (12 h reaction time). R f (70:30 Hexanes/EtOAc) = 0.40; IR (neat): 3409, 2979, 2935, 1692, 1508, 1457, 1392, 1366, 1244, 1167, 1028, 741 cm -1 ; 1 H NMR (400 MHz): δ 8.94 (br s, 1 H, NH), 7.59 (d, J = 7.8 Hz, 1 H), 7.37 (dd, J = 8.1, 0.7 Hz, 1 H), 7.2 (m, 1 H), 7.12 (m, 1 H), 4.96 (s, 1 H), 4.75 (br s, 1 H, NH), 4.25 (m, 4 H), 3.42 (br s, 2H), 2.96 (t, J = 6.6 Hz, 2 H), 1.44 (s, 9 H), 1.29 (td, J = 7.1, 0.7 Hz, 6 H); 13 C NMR (100 MHz): δ 167.6, 156.2, 136.4, 136.3, 127.7, 125.9, 122.9, 119.8, 119.2, 122.6, 111.5, 62.7, 62.7, 49.5, 41.3, 28.7, 25.0, 14.3; HRMS (ESI) m/z calculated for C 22 H 30 N 2 O 6 Na [M+Na] , found Spectral data is in accordance with previously reported data [3]. S9

10 Diethyl 2-(1-(tert-butoxycarbonyl)-3-(2-((tert-butoxycarbonyl)amino)ethyl)-1H-indol-2yl) malonate (Table 1, Entry 6; R = Boc). According to the general procedure, N,N -di-boctryptamine (50 mg, 0.14 mmol), diethyl bromomalonate (50 μl, 0.28 mmol), 4- methoxytriphenylamine (77 mg, 0.28 mmol) and tris(2,2 -bipyridyl)ruthenium(ii) chloride hexahydrate (1.0 mg, 1.4 µmol) afforded the coupled product (62 mg, 85%) as a beige solid after purification on SiO 2 (4:1 hexanes/etoac) (12 h reaction time). R f (80:20 Hexanes/EtOAc) = 0.25; IR (neat): 3363, 2980, 2360, 2342, 1722, 1456, 1366, 1329, 1233, 1162, 1131, 1039, 757 cm -1 ; 1 H NMR (400 MHz): δ 8.02 (d, J = 8.4 Hz, 1 H), 7.57 (d, J = 7.7 Hz, 1 H), 5.21 (s, 1 H), 4.89 (br s, 1 H, NH), (m, 4 H), 3.40 (d, J = 5.7 Hz, 2 H), 2.88 (t, J = 6.4 Hz, 2 H), 1.66 (s, 9 H), 1.43 (s, 9 H), 1.24 (t, J = 7.2 Hz, 3 H); 13 C NMR (100 MHz): δ 166.5, 156.0, 150.5, 135.6, 129.1, 129.0, 124.7, 122.6, 119.5, 118.9, 115.8, 84.4, 79.2, 77.2, 61.8, 49.9, 40.2, 28.4, 28.2, 24.7, 14.1; HRMS (ESI) m/z calculated for C 27 H 39 N 2 O 8 [M+1] , found S10

11 (S)-Diethyl 2-(3-(2-((tert-butoxycarbonyl)amino)-3-methoxy-3-oxopropyl)-1H-indol-2-yl) malonate (Table 1, Entry 7). According to the general procedure, N-Boc-tryptophan methyl ester (50 mg, 0.16 mmol), diethyl bromomalonate (53 μl, 0.31 mmol), 4-methoxytriphenylamine (87 mg, 0.31 mmol) and tris(2,2 -bipyridyl)ruthenium(ii) chloride hexahydrate (1.0 mg, 1.6 µmol) afforded the coupled product (60 mg, 77%) as a tan solid after purification on SiO 2 (4:1 hexanes/etoac) (20 h reaction time). R f (75:25 hexanes/etoac) = 0.24; IR (neat): 3399, 2982, 1748, 1640, 1368, 1267, 1028 cm -1 ; 1 H NMR (400 Mhz): δ 8.93 (br s, 1 H, NH), 7.52 (d, J = 8.0 Hz, 1 H), 7.33 (d, J = 8.0 Hz, 1 H), 7.17 (td, J = 7.5, 1.2 Hz, 1 H), (m, 1 H), 5.24 (d, J = 8.0 Hz, 1 H), 4.96 (s, 1 H, NH), (m, 1 H); (m, 4 H); 3.59 (s, 3 H); 3.26 (d, J = 5.9 Hz, 2 H); 1.39 (s, 6 H); 1.27 (td, J = 7.1, 1.5 Hz, 6 H); 13 C NMR (100 MHz): δ 172.6, 167.3, 155.2, 136.0, 127.7, 126.6, 122.7, 119.7, 119.0, 111.2, 109.4, 79.8, 62.5, 54.1, 52.3, 49.3, 28.3, 28.0, 27.0, 14.1, 14.0; HRMS (ESI) m/z calculated for C 24 H 32 N 2 O 8 [M+Na] , found S11

12 Diethyl 2-(3-(3-methoxy-3-oxopropyl)-1H-indol-2-yl)malonate (Table 1, Entry 8). According to the general procedure, methyl indole-3-propionate (50 mg, 0.25 mmol), diethyl bromomalonate (83 μl, 0.50 mmol), 4-methoxytriphenylamine (0.14 g, 0.50 mmol) and tris(2,2 -bipyridyl)ruthenium(ii) chloride hexahydrate (2.0 mg, 2.5 µmol) afforded the coupled product (70 mg, 78%) as a brown semi-solid oil after purification on SiO 2 (9:1 hexanes/etoac) (18 h reaction time). R f (90:10 Hexanes/EtOAc) = 0.19; IR (neat): 3399, 2983, 1734, 1460, 1369, 1267, 1202, 1029, 744 cm -1 ; 1 H NMR (400 MHz): δ 8.91 (br s, 1 H, NH), 7.56 (m, 1 H), 7.36 (m, 1 H), 7.19 (ddd, J = 8.1, 7.1, 1.2 Hz, 1 H), 7.1 (m, 1H), 5.1 (s, 1H) 4.23 (m, 4H), 3.64 (s, 3H), 3.09 (t, J = 7.5 Hz, 2H), 2.66 (t, J = 7.5 Hz, 2H), 1.28 (t, J = 3.0 Hz, 6H); 13 C NMR (100 MHz): δ 173.9, 167.6, 136.2, 127.4, 127.4, 125.5, 122.7, 119.7, 118.8, 113.7, 111.6, 62.6, 51.8, 49.4, 35.0, 19.7, 14.2; HRMS (ESI) m/z calculated for C 19 H 23 NO 6 [M+Na] , found S12

13 Diethyl 2-(4-bromo-1-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl)malonate (Table 1, Entry 9). According to the general procedure, 5-bromo-1-methyl-7-azaindole (0.10 g, 0.45 mmol), diethyl bromomalonate (0.15 ml, 0.90 mmol), 4-methoxytriphenylamine (0.25 g, 0.90 mmol,) and tris(2,2 -bipyridyl)ruthenium(ii) chloride hexahydrate (3.4 mg, 4.5 µmol) afforded the coupled product (0.95 g, 49%) as a yellow oil after purification on SiO 2 (9:1 hexanes/etoac) (18 h reaction time). R f (90:10 Hexanes/EtOAc) = 0.31; IR (neat cm-1) 2982, 2927, 2854, 2361, 2340, 1738, 1533, 1476, 1402, 1369, 1311, 1216, 1155, 1031, 761 cm -1 ; 1 H NMR (500 MHz): δ 8.25 (d, J = 2.2 Hz, 1 H), 7.89 (dd, J = 2.2, 0.5 Hz, 1 H), 6.44 (s, 1 H), 4.84 (s, 1 H), (m, 4 H), 3.73 (s, 3 H), 1.22 (t, J = 7.1 Hz, 6 H); 13 C NMR (100 MHz): δ 166.4, 147.0, 143.7, 133.3, 130.6, 121.3, 111.9, 100.4, 62.6, 51.3, 28.8, 14.1; HRMS (ESI) m/z calculated for C 15 H 18 BrN 2 O 4 [M+1] , found S13

14 Diethyl 2-(3-(((2S,5R)-5-benzyl-3,6-dioxopiperazin-2-yl)methyl)-1H-indol-2-yl)malonate (Table 1, Entry 10). According to the general procedure, tryptophan/phenylalanine diketopiperzine (50 mg, 0.15 mmol), diethyl bromomalonate (51 μl, 0.30 mmol), 4- methoxytriphenylamine (83 mg, 0.30 mmol) and tris(2,2 -bipyridyl)ruthenium(ii) chloride hexahydrate (1.1 mg, 1.5 µmol) afforded the coupled product (49 mg, 68%) as a grayish solid after purification on SiO 2 (1:1 hexanes/etoac 100% CH 2 Cl 2 9:1 CH 2 Cl 2 /MeOH) (18 h reaction time). R f (90:10 CH 2 Cl 2 /MeOH) = 0.55; IR (neat): 3297, 2983, 2364, 1730, 1674, 1456, 2323, 1215, 1092, 1028, 910, 740 cm -1 ; 1 H NMR (300 MHz): δ 9.15 (s, 1 H, NH), 7.59 (d, J = 7.7 Hz, 1 H), (m, 6 H), 6.84 (d, J = 1.6 Hz, 1 H), 6.39 (d, J = 1.8 Hz, 1 H), 4.80 (s, 1 H), (m, 4 H), 3.34 (dd, J = 14.8, 2.6 Hz, 1 H), 3.05 (dd, J = 13.7, 3.8 Hz, 1 H), 2.70 (dd, J = 13.6, 6.7 Hz, 1 H), 2.11 (dd, J = 14.6, 9.3 Hz, 1 H), 1.96 (br s, 1 H), (m, 6 H); 13 C NMR (100 MHz): δ 167.9, 167.7, 167.6, 166.2, 136.4, 135.6, 130.5, 129.2, 127.7, 127.2, 127.1, 123.4, 120.4, 119.2, 111.7, 109.5, 76.9, 63.3, 62.8, 56.6, 55.9, 49.3, 40.3, 29.7, 14.3; HRMS (ESI) m/z calculated for C 24 H 29 N 3 NaO 6 [M+Na] , found S14

15 Br N H O NH NHBoc OMe O EtO 2 C Ru(bpy) 3 Cl 2 p-ch 3 OC 6 H 4 NPh 2 visible light, DMF N H O NH NHBoc OMe O Diethyl 2-(3-((S)-2-((tert-butoxycarbonyl)amino)-3-(((S)-1-methoxy-1-oxo-3-phenylpropan- 2-yl)amino)-3-oxopropyl)-1H-indol-2-yl)malonate (Table 1, Entry 11). According to the general procedure, tryptophan-phenylalanine dipeptide (50 mg, 0.10 mmol), diethyl bromomalonate (51 μl, 0.20 mmol), 4-methoxytriphenylamine (59 mg, 0.20 mmol) and tris(2,2 -bipyridyl)ruthenium(ii) chloride hexahydrate (0.8 mg, 8.0 µmol) afforded the coupled product (45 mg, 67%) as a tan solid after purification on SiO 2 (7:3 hexanes/etoac) (12 h reaction time). R f (70:30 Hexanes/EtOAc) = 0.25; IR (neat): 3388, 3064, 2982, 2936, 1745, 1674, 1497, 1459, 1368, 1246, 1211, 1180, 1028, cm -1 ; 1 H NMR (300 MHz): δ 9.03 (s, 1 H, NH), 7.57 (d, J = 7.8 Hz, 1 H), 7.33 (d, J = 8.1 Hz, 1 H), (m, 4 H), 6.80 (br s, 2 H), 6.19 (d, J = 7.2 Hz, 1 H), 5.36 (br s, 1 H, NH), 5.14 (br s, 1 H, NH), 4.47 (d, J = 5.6 Hz, 2 H), (m, 4 H), 3.48 (s, 2 H), (m, 1 H), (m, 1 H), 2.89 (d, J = 5.1 Hz, 2 H), 1.77 (br s, 1H), 1.42 (s, 9 H), (m, 6 H); 13 C NMR (100 MHz): δ 171.4, 171.3, 171.2, 155.4, 136.3, 135.6, 129.1, 128.4, 127.5, 127.0, 123.4, 122.2, 119.6, 118.8, 111.3, 110.2, 80.1, 60.4, 55.2, 53.2, 52.2, 37.9, 28.3, 21.0, 14.2; HRMS (ESI) m/z calculated for C 33 H 41 N 3 NaO 9 [M+Na] , found S15

16 Diethyl 2-(3-acetyl-1-methyl-1H-pyrrol-2-yl)malonate (Table 1, Entry 12). According to the general procedure, 3-acetyl-1-methylpyrrole (50 mg, 0.25 mmol), diethyl bromomalonate (83 μl, 0.50 mmol), 4-methoxytriphenylamine (0.14 g, 0.50 mmol) and tris(2,2 bipyridyl)ruthenium(ii) chloride hexahydrate (2.0 mg, 2.5 µmol) afforded the coupled product (70 mg, 78%) as a brown oil after purification on SiO 2 (9:1 hexanes/etoac) (18 h reaction time). R f (90:10 Hexanes/EtOAc) = 0.14; IR (neat) : 3410, 1727, 1647, 1504, 1219, 1146, 1021 cm -1 ; 1 H NMR (300 MHz): δ 6.61 (s, 1 H), 6.53 (dd, J = 15.3, 2.9 Hz,1 H), (m, 4 H), 3.63 (s, 3 H), 2.40 (s, 3 H), 1.27 (t, J = 7.1 Hz, 6 H); 13 C NMR (100 MHz): δ 195.5, 167.5, 127.8, 123.7, 122.5, 110.4, 61.9, 48.5, 35.2, 28.4, 14.0, 13.9; HRMS (ESI) m/z calculated for C 14 H 20 NO 5 [M+1] , found S16

17 Diethyl 2-(5-ethyl-1H-pyrrol-2-yl) malonate (Table 1, Entry 13). According to the general procedure, 2-ethylpyrrole (50 mg, 0.53 mmol), diethyl bromomalonate (0.25 ml, 1.0 mmol,), 4- methoxytriphenylamine (0.29 g, 1.0 mmol) and tris(2,2 -bipyridyl)ruthenium(ii) chloride hexahydrate (3.9 mg, 5.3 µmol) afforded the coupled product (90 mg, 68%) as a dark oil after purification on SiO 2 (9:1 hexanes/etoac) (12 h reaction time). R f (90:10 Hexanes/EtOAc) = 0.28; IR (neat) 3398, 2981, 2936, 1736, 1466, 1370, 1304, 1190, 1150 cm -1 ; 1 H NMR (400 MHz): δ 8.72 (br s, 1 H, NH), 6.02 (dd, J = 2.9 Hz, 1 H), 5.83 (t, J = 3.0 Hz, 1 H), 4.69 (s, 1 H), (m, 4 H), 2.63 (q, J = 7.6 Hz, 2 H), (m, 6 H); 13 C NMR (100 MHz): δ 168.2, 135.6, 120.0, 108.9, 104.4, 62.2, 51.4, 30.0, 21.1, 14.2, 13.7, 13.6; HRMS (ESI) m/z calculated for [M+1] , found S17

18 Diethyl 2-(furan-2-yl)malonate 4 (Table 1, Entry 14). A flame dried 10 ml round bottom flask was equipped with a rubber septum and magnetic stir bar and was charged with tris(2,2 bipyridyl)ruthenium(ii) chloride hexahydrate (5.9 µmol, 0.01 equiv), 4-methoxytriphenylamine (1.2 mmol, 2.0 equiv), diethyl bromomalonate (0.59 mmol, 1.0 equiv) and DMF (2 ml). The mixture was degassed via the freeze-pump-thaw method, after which freshly distilled furan (0.22 ml, 3.0 mmol) was added and exposed to blue light for 24 h. The reaction mixture was worked up in accordance with the general procedure. The coupled product (87 mg, 67%) was isolated as a yellow oil after purification on SiO 2 (95:5 hexanes/etoac). R f (90:10 Hexanes/EtOAc) = 0.13; 1 H NMR (300 MHz): δ (m, 1 H), 6.44 (dd, J = 3.3, 0.7 Hz, 1 H), (m, 1 H), 4.77 (s, 1 H), 4.25 (q, J = 7.1 Hz, 4 H), (m, 7 H). S18

19 Luminescence Quenching of Ru(bpy) 3 Cl 2 Emission intensities were measured using a Jobin Yvon Horiba FluoroMax 3 Fluorimeter equipped with an excitation/emission monochromator. Samples were excited at 452 nm and emission peaks were observed at 617 nm. Typical procedure: A stock solution of 1.47 mm Ru(bpy) 3 Cl 2 in DMF was prepared and degassed three times via freeze-pump-thaw method. The stock solution was then added to varying amounts of the tested quencher in a 1 cm quartz cuvette. Samples were prepared in five concentrations: 0.36M, 0.18M, 0.09M, 0.045M, and M. Figure S1: Luminescence Quenching of Ru(II)* by 4-Methoxytriphenylamine y = x + 1 R² = I/Io Methoxytriphenylamine [M] S19

20 References and Notes [1] Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory Chemicals, 3 rd ed.; Pergamon Press: Oxford, [2] Blue LEDs were purchased at [3] Reyes-Guiterrez, P. E.; Torres-Ochoa, R. O.; Martinez, R.; Miranda, L. D. Org. Biomol. Chem. 2009, 7, [4] Ghosh, S.; Pardo, S. N.; Salomon, R. G. J. Org. Chem. 1982, 47, S20

21 .esp O N C CO 2 Me CO 2 Me Chemical Shift (ppm) S21

22 esp O N CO 2 Me C CO 2 Me Chemical Shift (ppm) S22

23 S23

24 S24

25 Br N Table 1, entry 2) S25

26 Br N Table 1, entry 2) S26

27 N H Me N H (Table 1, entry 3) O OMe S27

28 Me N H (Table 1, entry 3) S28

29 O OMe EtO 2 C O N H CO N 2 Me H N NHBoc N (Table 1, Hentry 4) O OMe S29

30 EtO 2 C N CO 2 Me (Table 1, entry 4) S30

31 Br N H (Table 1, entry 5) S31

32 Br N H (Table 1, entry 5) S32

33 BocHN N H (Table 1, entry 6, R = H) S33

34 BocHN N H (Table 1, entry 6, R = H) S34

35 S35

36 S36

37 MeO 2 C NHBoc N H (Table 1, entry 7) S37

38 MeO 2 C NHBoc N H (Table 1, entry 7) S38

39 S39

40 S40

41 S41

42 S42

43 S43

44 S44

45 S45

46 S46

47 O N H (Table 1, entry 12) S47

48 O N H (Table 1, entry 12) S48

49 N H (Table 1, entry 13) S49

50 N H (Table 1, entry 13) S50

51 N H 13 O (Table 1, entry 14) S51