Supporting information

Supporting information Synthesis of Aryl Sulfides: Metal-Free C H Sulfenylation of Electron-Rich Arenes Thomas Hostier, a Vincent Ferey, b Gino Ricci, c Domingo Gomez Pardo a and Janine Cossy*, a a Laboratoire de Chimie Organique, Institute of Chemistry, Biology and Innovation (CBI), UMR 8231, ESPCI ParisTech/CNRS/PSL Research University, 10 rue Vauquelin, 75231-Paris Cedex 05, France. E-mail: janine.cossy@espci.fr b Chemistry and Biotechnology Development, Sanofi, 371 rue du Professeur Blayac, 34184- Montpellier Cedex 04, France. c Sanofi Process Development, 45 chemin de Mételine BP15, 04210-Sisteron Cedex, France. Table of contents 1. General experimental methods... 2 2. Optimization of reactions conditions... 2 3. Preparation of N-thiosuccinimides (5a-5f)... 3 4. Synthesis of thioarenes (2a-2v)... 5 5. References... 15 6. 7. 1 H and 13 C NMR spectra of N-thiosuccinimides (5a-5f)... 16 1 H and 13 C NMR spectra of thioarenes (2a-2v)... 29 1

1. General experimental methods All reactions were run under air unless otherwise specified. Trifluoroacetic acid (ReagentPlus, 99%) and other commercially available chemicals were purchased from Aldrich and used directly without purification. CH 2 Cl 2 was distilled over CaH 2 before use. NMR spectra were recorded on a Bruker AVANCE 400. 1 H NMR spectra were recorded at 400 MHz and data are reported as follows: chemical shift in ppm from tetramethylsilane (TMS) or residual protonated solvents as an internal standard (TMS δ 0.00 ppm, CDCl 3 δ 7.26 ppm, DMSO δ 2.50 ppm), multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet or overlap of nonequivalent resonances), integration. 13 C NMR spectra were recorded at 100 MHz and data are reported as follows: chemical shift in ppm with the solvent as an internal indicator (CDCl 3 δ 77.16 ppm, DMSO δ 39.52 ppm). TLCs were performed on Merck 60F 254 silica gel plates and visualized with UV lamp (254 nm), and by using a solution of phosphomolybdic acid in ethanol followed by heating. Flash column chromatographies were performed with Merck Geduran Si 60 silica gel (40-63 m). Mass spectra with electronic impact (MS-EI) were recorded from a Shimadzu GCMS-QP 2010S. Infrared (IR) were recorded with a Bruker TENSOR TM 27 (IRFT), wave-numbers are indicated in cm 1. High resolution mass spectra (HRMS) were performed by the Centre Regional de Microanalyse (Université Pierre et Marie Curie VI, Paris, France). Melting points were determined on a Büchi Melting Point M-560 apparatus and are uncorrected. PE = Petroleum ether TFA = Trifluoroacetic acid 2. Optimization of the reaction conditions General procedure In a 10 ml oven-dried vial, equipped with a rubber septum, were added methoxybenzene 1a (44 μl, 0.4 mmol, 1.0 equiv) and the sulfenylating reagent 3 5a (0.4 mmol, 1.0 equiv). Subsequently, dry CH 2 Cl 2 (0.5 M) was added into the vial, followed by the addition of TFA and the resulting solution was stirred at rt for 6 h (Note: TFA was directly added into the vial when used as the solvent). The reaction mixture was neutralized with a saturated solution of NaHCO 3 (15 ml) and extracted with CH 2 Cl 2 (3 x 15 ml). The combined organic extracts were dried over anhydrous Na 2 SO 4, filtered and concentrated under reduced pressure. The yield of 1-methoxy-4-(phenylsulfanyl)benzene 2a was determined by 1 H NMR using 1,3,5-trimethoxybenzene as the internal standard. 2

3. Preparation of N-thiosuccinimides (5a-5f) General procedure According to the literature procedure, 1 sulfuryl chloride (1.05 equiv) was added dropwise to a solution of the thiol derivative (1.0 equiv) and Et 3 N (0.1 equiv) in anhydrous CH 2 Cl 2 (1 M) at 0 C, under argon. After stirring for 15 min, the reaction mixture was stirred for 1 h at rt and then cooled to 0 C. The resulting solution was transferred dropwise via cannula to a solution of succinimide (1.0 equiv) and Et 3 N (1.3 equiv) in anhydrous CH 2 Cl 2 (1 M) at 0 C. The reaction mixture was allowed to warm to rt and stirred for 1 h. The solution was diluted with H 2 O (20 ml for 5 mmol), extracted with CH 2 Cl 2 (3 x 20 ml for 5 mmol), dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel using a mixture of PE/EtOAc or CH 2 Cl 2 /Et 2 O as the eluent to afford the expected product 5. 1-(Phenylsulfanyl)pyrrolidine-2,5-dione (5a) 1 Formula: C 10 H 9 NO 2 S Mw = 207.94 g.mol 1 Compound 5a was synthesized from thiophenol (1.04 ml, 9.89 mmol). Purification by flash column chromatography (PE/EtOAc = 7:3) afforded 5a (1.91 g, 9.20 mmol, 93%) as a white solid. The spectral data are in agreement with the literature report. 1 mp: 115-116 C. IR (neat): ν max 3065, 2985, 2935, 1712, 1470, 1439, 1426, 1295, 1243, 1145, 1080, 1001 cm 1. 1 H NMR (CDCl 3, 400 MHz): δ 7.64-7.59 (m, 2H), 7.38-7.31 (m, 3H), 2.82 (s, 4H). 13 C NMR (CDCl 3, 100 MHz): δ 176.5 (2C), 134.0, 132.5 (2C), 130.1, 129.5 (2C), 28.7 (2C). MS: Compound 5a is not stable under GC analysis. 1-[(4-Methylphenyl)sulfanyl]pyrrolidine-2,5-dione (5b) 1 Formula: C 11 H 11 NO 2 S Mw = 221.28 g. mol 1 Compound 5b was synthesized from p-toluenethiol (251 mg, 1.98 mmol). Purification by flash column chromatography (PE/EtOAc = 7:3) afforded 5b (406 mg, 1.84 mmol, 93%) as a white solid. The spectral data are in agreement with the literature report. 1 mp: 113-115 C. IR (neat): ν max 3060, 2941, 2922, 1712, 1596, 1488, 1428, 1405, 1296, 1240, 1143, 1007 cm 1. 1 H NMR (CDCl 3, 400 MHz): δ 7.59-7.56 (m, 2H), 7.15-7.12 (m, 2H), 2.77 (s, 4H), 2.33 (s, 3H). 1 Saravanan, P.; Anbarasan, P. Org. Lett. 2014, 16, 848. 3

13 C NMR (CDCl 3, 100 MHz): δ 176.6 (2C), 141.0, 133.8 (2C), 130.5, 130.2 (2C), 28.7 (2C), 21.5. MS m/z (relative intensity): 221 (M +, 67), 139 (20), 123 (55), 79 (31), 77 (43), 70 (16), 65 (16), 55 (100). 1-[(4-Methoxyphenyl)sulfanyl]pyrrolidine-2,5-dione (5c) 1 Formula: C 11 H 11 NO 3 S Mw = 237.27 g. mol 1 Compound 5c was synthesized from 4-methoxythiophenol (0.314 ml, 2.47 mmol). Purification by flash column chromatography (PE/EtOAc = 6:4) afforded 5c (400 mg, 1.69 mmol, 68%) as a white solid. The spectral data are in agreement with the literature report. 1 mp: 106-110 C. IR (neat): ν max 2945, 2844, 1715, 1591, 1569, 1493, 1461, 1446, 1293, 1255, 1238, 1150, 1104, 1090, 1022, 1009 cm 1. 1 H NMR (CDCl 3, 400 MHz): δ 7.72 (d, J = 8.8 Hz, 2H), 6.83 (d, J = 8.8 Hz, 2H), 3.79 (s, 3H), 2.74 (s, 4H). 13 C NMR (CDCl 3, 100 MHz): δ 176.7 (2C), 161.8, 137.4 (2C), 124.6, 114.8 (2C), 55.5, 28.7 (2C). MS m/z (relative intensity): 237 (M +, 53), 140 (17), 139 (100), 124 (10), 96 (20), 95 (18), 70 (18), 55 (41). 1-[(4-Bromophenyl)sulfanyl]pyrrolidine-2,5-dione (5d) 1 Formula: C 10 H 8 BrNO 2 S Mw = 286.15 g. mol 1 Compound 5d was synthesized from 4-bromothiophenol (394 mg, 1.98 mmol). Purification by flash column chromatography (PE/EtOAc = 6:4) afforded 5d (319 mg, 1.12 mmol, 56%) as a white solid. The spectral data are in agreement with the literature report. 1 mp: 140-144 C. IR (neat): ν max 2925, 2853, 1715, 1471, 1423, 1383, 1303, 1247, 1232, 1134, 1085, 1069, 1003 cm 1. 1 H NMR (CDCl 3, 400 MHz): δ 7.52-7.49 (m, 2H), 7.47-7.44 (m, 2H), 2.81 (s, 4H). 13 C NMR (CDCl 3, 100 MHz): δ 176.3 (2C), 134.4 (2C), 132.9, 132.7 (2C), 124.9, 28.7 (2C). MS: Compound 5d is not stable under GC analysis. 4

1-[(4-Nitrophenyl)sulfanyl]pyrrolidine-2,5-dione (5e) 2 Formula: C 10 H 8 N 2 O 4 S Mw = 252.25 g. mol 1 Compound 5e was synthesized from 4-nitrothiophenol (384 mg, 1.98 mmol). Purification by flash column chromatography (CH 2 Cl 2 /Et 2 O = 100:0 to 98:2) afforded 5e (273 mg, 1.08 mmol, 55%) as a pale yellow solid. The spectral data are in agreement with the literature report. 2 mp: 174-176 C. IR (neat): ν max 3105, 2951, 1728, 1598, 1583, 1514, 1342, 1294, 1248, 1221, 1127, 1086, 1006 cm 1. 1 H NMR (CDCl 3, 400 MHz): δ 8.19-8.15 (m, 2H), 7.45-7.42 (m, 2H), 2.97 (s, 4H). 13 C NMR (CDCl 3, 100 MHz): δ 175.8 (2C), 147.5, 143.1, 127.7 (2C), 124.6 (2C), 28.7 (2C). MS: Compound 5e is not stable under GC analysis. 1-(Ethylsulfanyl)pyrrolidine-2,5-dione (5f) 3 Formula: C 6 H 9 NO 2 S Mw = 159.21 g. mol 1 Compound 5f was synthesized from ethanethiol (0.740 ml, 9.89 mmol). Purification by flash column chromatography (PE/EtOAc = 1:1) afforded 5f (969 mg, 6.09 mmol, 62%) as a white solid. The spectral data are in agreement with the literature report. 3 mp: 60-62 C. IR (neat): ν max 2966, 2931, 2871, 1712, 1456, 1419, 1376, 1310, 1262, 1244, 1145, 1006 cm 1. 1 H NMR (CDCl 3, 400 MHz): δ 2.86 (q, J = 7.4 Hz, 2H), 2.82 (s, 4H), 1.20 (t, J = 7.4 Hz, 3H). 13 C NMR (CDCl 3, 100 MHz): δ 177.3 (2C), 31.8, 28.7 (2C), 13.1. MS: Compound 5f is not stable under GC analysis. 4. Synthesis of thioarenes (2a-2v) General procedure A 10 ml oven-dried vial, equipped with a rubber septum, was charged with arene 1 (1.0 equiv) and N-thiosuccinimide 5 (1.0 equiv). Dry CH 2 Cl 2 (0.5 M) was added into the vial, followed by TFA (15 equiv), and the resulting solution was stirred at rt for 6 h. The reaction mixture was neutralized with a saturated solution of NaHCO 3 (15 ml) and extracted with CH 2 Cl 2 (3 x 15 ml). The combined organic extracts were dried over anhydrous Na 2 SO 4, filtered and concentrated under reduced pressure. The 2 Savarin, S.; Srogl, J.; Liebeskind, L. S. Org. Lett. 2002, 4, 4309. 3 Abe, Y.; Nakabayashi, T.; Tsurugi, J. Bull. Chem. Soc. Jpn. 1973, 46, 1898. 5

crude product was purified by flash column chromatography on silica gel using a mixture of PE/EtOAc or CH 2 Cl 2 /Et 2 O as the eluent to afford the expected product 2. 1-Methoxy-4-(phenylsulfanyl)benzene (2a) 1 Formula: C 13 H 12 OS Mw = 216.30 g. mol 1 Compound 2a was synthesized from methoxybenzene 1a (53 μl, 0.48 mmol) and 1-(phenylsulfanyl)pyrrolidine-2,5-dione 5a (100 mg, 0.48 mmol). Purification by flash column chromatography (PE/EtOAc = 100:0 to 95:5) afforded 2a (79 mg, 0.37 mmol, 76%) as a white solid. The spectral data are in agreement with the literature report. 1 mp: 28-30 C. IR (neat): ν max 3061, 2998, 2970, 2946, 2842, 1589, 1491, 1475, 1460, 1437, 1286, 1244, 1175, 1100, 1078, 1028, 1006 cm 1. 1 H NMR (CDCl 3, 400 MHz): δ 7.36-7.32 (m, 2H), 7.18-7.13 (m, 2H), 7.10-7.04 (m, 3H), 6.84-6.80 (m, 2H), 3.74 (s, 3H). 13 C NMR (CDCl 3, 100 MHz): δ 160.0, 138.7, 135.5 (2C), 129.1 (2C), 128.3 (2C), 125.9, 124.4, 115.1 (2C), 55.5. MS m/z (relative intensity): 216 (M +, 100), 201 (51), 129 (24), 77 (16), 63 (9), 51 (16). 2,4-Dimethyl-1-(phenylsulfanyl)benzene (2b) 1 Formula: C 14 H 14 S Mw = 214.33 g. mol 1 Compound 2b was synthesized from 1,3-dimethylbenzene 1b (59 μl, 0.48 mmol) and 1-(phenylsulfanyl)pyrrolidine-2,5-dione 5a (100 mg, 0.48 mmol). Purification by flash column chromatography (PE/EtOAc = 100:0 to 98:2) afforded 2b (38 mg, 0.19 mmol, 37%) as a clear oil. The spectral data are in agreement with the literature report. 1 IR (neat): ν max 3057, 2918, 1583, 1476, 1438, 1376, 1232, 1084, 1054, 1024 cm 1. 1 H NMR (CDCl 3, 400 MHz): δ 7.21 (d, J = 7.8 Hz, 1H), 7.16-7.11 (m, 2H), 7.06-7.00 (m, 4H), 6.89 (m, 1H), 2.25 (s, 3H), 2.24 (s, 3H). 13 C NMR (CDCl 3, 100 MHz): δ 141.0, 138.7, 137.5, 134.6, 131.7, 129.4, 129.1 (2C), 128.4 (2C), 127.7, 125.8, 21.2, 20.7. MS m/z (relative intensity): 214 (M +, 100), 199 (17), 184 (12), 166 (11), 165 (13), 136 (26), 135 (22), 106 (14), 105 (42), 103 (14), 92 (13), 91 (25), 79 (16), 78 (16), 77 (47), 65 (18), 51 (32). 2,4-Dimethoxy-1-(phenylsulfanyl)benzene (2c) 1 Formula: C 14 H 14 O 2 S Mw = 246.32 g. mol 1 6

Compound 2c was synthesized from 1,3-dimethoxybenzene 1c (64 μl, 0.48 mmol) and 1-(phenylsulfanyl)pyrrolidine-2,5-dione 5a (100 mg, 0.48 mmol). Purification by flash column chromatography (PE/EtOAc = 98:2) afforded 2c (58 mg, 0.23 mmol, 49%) as a white solid. The spectral data are in agreement with the literature report. 1 mp: 62-65 C. IR (neat): ν max 3016, 2965, 2936, 2836, 1592, 1572, 1477, 1459, 1435, 1412, 1302, 1286, 1253, 1209, 1164, 1144, 1104, 1085, 1074, 1024 cm 1. 1 H NMR (CDCl 3, 400 MHz): δ 7.25 (d, J = 8.4 Hz, 1H), 7.15-7.09 (m, 2H), 7.05-6.99 (m, 3H), 6.43 (d, J = 2.5 Hz, 1H), 6.40 (dd, J = 8.4, 2.5 Hz, 1H), 3.72 (s, 3H), 3.70 (s, 3H). 13 C NMR (CDCl 3, 100 MHz): δ 161.9, 160.4, 137.8, 136.8, 128.8 (2C), 127.7 (2C), 125.5, 112.1, 105.4, 99.3, 56.0, 55.5. MS m/z (relative intensity): 246 (M +, 100), 231 (19), 200 (11), 198 (23), 171 (21), 160 (11), 115 (13), 95 (14), 79 (18), 77 (23), 69 (19), 65 (13), 63 (12), 51 (40). 4-Bromo-2-methoxy-1-(phenylsulfanyl)benzene (2d) 1 Formula: C 13 H 11 BrOS Mw = 295.19 g. mol 1 Compound 2d was synthesized from 3-bromo-1-methoxybenzene 1d (61 μl, 0.48 mmol) and 1-(phenylsulfanyl)pyrrolidine-2,5-dione 5a (100 mg, 0.48 mmol). Purification by flash column chromatography (PE/EtOAc = 100:0 to 98:2) afforded 2d (122 mg, 0.42 mmol, 86%) as a pale yellow solid. The spectral data are in agreement with the literature report. 1 mp: 70-72 C. IR (neat): ν max 3096, 3005, 2965, 2931, 2852, 2831, 1582, 1557, 1473, 1431, 1385, 1283, 1229, 1182, 1156, 1081, 1028, 1019 cm 1. 1 H NMR (CDCl 3, 400 MHz): δ 7.32-7.27 (m, 3H), 7.25-7.20 (m, 4H), 6.82 (dd, J = 8.7, 2.7 Hz, 1H), 3.81 (s, 3H). 13 C NMR (CDCl 3, 100 MHz): δ 160.0, 136.2, 135.3, 129.6 (2C), 129.3 (2C), 128.4, 126.7, 126.6, 118.9, 114.6, 55.8. MS m/z (relative intensity): 296 (M +, 63), 294 (M +, 64), 281 (12), 279 (13), 200 (100), 184 (25), 172 (60), 171 (90), 139 (19), 138 (21), 123 (32), 108 (33), 95 (28), 77 (47), 69 (47), 65 (28), 63 (71), 62 (19), 51 (80). 1-Methoxy-2-methyl-4-(phenylsulfanyl)benzene (2e) Formula: C 14 H 14 OS Mw = 230.33 g. mol 1 Compound 2e was synthesized from 2-methyl-1-methoxybenzene 1e (55 μl, 0.44 mmol) and 1-(phenylsulfanyl)pyrrolidine-2,5-dione 5a (90.9 mg, 0.44 mmol). Purification by flash column chromatography (PE/EtOAc = 100:0 to 98:2) afforded 2e (79 mg, 0.34 mmol, 78%) as an off-white solid. 7

mp: 63-65 C. IR (neat): ν max 3000, 2953, 2923, 2831, 1579, 1491, 1476, 1459, 1439, 1293, 1248, 1179, 1136, 1102, 1081, 1030 cm 1. 1 H NMR (CDCl 3, 400 MHz): δ 7.22 (ddd, J = 8.4, 2.4, 0.6 Hz, 1H), 7.19 (m, 1H), 7.15-7.11 (m, 2H), 7.08-7.06 (m, 2H), 7.03 (m, 1H), 6.71 (d, J = 8.3 Hz, 1H), 3.74 (s, 3H), 2.10 (s, 3H). 13 C NMR (CDCl 3, 100 MHz): δ 158.2, 139.1, 136.5, 133.1, 129.0 (2C), 128.1, 128.0 (2C), 125.7, 123.4, 110.8, 55.5, 16.3. MS m/z (relative intensity): 230 (M +, 100), 215 (59), 172 (15), 153 (11), 115 (11), 109 (11), 78 (15), 77 (29), 65 (19), 52 (12), 51 (41). HRMS: calcd for (C 14 H 14 OS) + : 230.0760, found : 230.0760. 1,3,5-Trimethyl-2-(phenylsulfanyl)benzene (2f) 1 Formula: C 15 H 16 S Mw = 228.35 g. mol 1 Compound 2f was synthesized from 1,3,5-trimethylbenzene 1f (67 μl, 0.48 mmol) and 1-(phenylsulfanyl)pyrrolidine-2,5-dione 5a (100 mg, 0.48 mmol). Purification by flash column chromatography (PE 100%) afforded 2f (89 mg, 0.39 mmol, 81%) as a clear oil. The spectral data are in agreement with the literature report. 1 IR (neat): ν max 3057, 3019, 2950, 2919, 2851, 1601, 1582, 1477, 1462, 1438, 1375, 1085, 1060, 1024 cm 1. 1 H NMR (CDCl 3, 400 MHz): δ 7.24-7.19 (m, 2H), 7.12-7.06 (m, 3H), 7.00-6.96 (m, 2H), 2.45 (s, 6H), 2.37 (s, 3H). 13 C NMR (CDCl 3, 100 MHz): δ 143.9 (2C), 139.4, 138.5, 129.5 (2C), 129.0 (2C), 127.1, 125.6 (2C), 124.6, 21.8 (2C), 21.3. MS m/z (relative intensity): 228 (M +, 100), 150 (51), 149 (18), 135 (11), 119 (20), 115 (13), 105 (11), 91 (32), 77 (16). 1,3,5-Trimethoxy-2-(phenylsulfanyl)benzene (2g) 1 Formula: C 15 H 16 O 3 S Mw = 276.35 g. mol 1 Compound 2g was synthesized from 1,3,5-trimethoxybenzene 1g (82.0 mg, 0.48 mmol) and 1-(phenylsulfanyl)pyrrolidine-2,5-dione 5a (100 mg, 0.48 mmol). Purification by flash column chromatography (PE/EtOAc = 95:5 to 9:1) afforded 2g (80 mg, 0.29 mmol, 60%) as a white solid. The spectral data are in agreement with the literature report. 1 mp: 123-126 C. IR (neat): ν max 3011, 2971, 2941, 2839, 1738, 1576, 1467, 1454, 1436, 1412, 1339, 1228, 1204, 1185, 1163, 1123, 1093, 1032, 1022 cm 1. 8

1 H NMR (CDCl 3, 400 MHz): δ 7.17-7.13 (m, 2H), 7.04-7.01 (m, 3H), 6.22 (s, 2H), 3.87 (s, 3H), 3.80 (s, 6H). 13 C NMR (CDCl 3, 100 MHz): δ 163.0, 162.6 (2C), 138.8, 128.6 (2C), 125.7 (2C), 124.4, 98.7, 91.3 (2C), 56.4 (2C), 55.5. MS m/z (relative intensity): 276 (M +, 100), 230 (15), 228 (16), 201 (11), 115 (10), 91 (13), 69 (17). 6-(Phenylsulfanyl)-2H-1,3-benzodioxol-5-ol (2h) Formula: C 13 H 10 O 3 S Mw = 246.28 g. mol 1 Compound 2h was synthesized from 1,3-benzodioxol-5-ol 1h (56.4 mg, 0.40 mmol) and 1-(phenylsulfanyl)pyrrolidine-2,5-dione 5a (82.9 mg, 0.40 mmol). Purification by flash column chromatography (PE/EtOAc = 95:5) afforded 2h (97 mg, 0.39 mmol, 98%) as a brown solid. mp: 70-72 C. IR (neat): ν max 3415, 3056, 2895, 1618, 1582, 1500, 1469, 1439, 1371, 1278, 1221, 1177, 1111, 1079, 1034, 1006 cm 1. 1 H NMR (CDCl 3, 400 MHz): δ 7.19-7.14 (m, 2H), 7.07 (m, 1H), 7.01-6.98 (m, 2H), 6.86 (s, 1H), 6.56 (s, 1H), 6.35 (1H), 5.89 (s, 2H). 13 C NMR (CDCl 3, 100 MHz): δ 153.7, 151.1, 141.8, 136.6, 129.3 (2C), 126.5 (2C), 126.2, 114.7, 105.7, 101.8, 97.5. MS m/z (relative intensity): 246 (M +, 100), 183 (34), 169 (12), 168 (21), 141 (12), 140 (66), 115 (18), 110 (18), 109 (25), 99 (13), 85 (15), 82 (18), 77 (28), 69 (49), 66 (25), 65 (28), 53 (79), 51 (59). HRMS: calcd for C 13 H 11 O 3 S (M+H) + : 247.0423, found : 247.0424. Methyl 2-hydroxy-5-(phenylsulfanyl)benzoate (2i) Formula: C 14 H 12 O 3 S Mw = 260.31 g. mol 1 Compound 2i was synthesized from methyl 2-hydroxybenzoate 1i (56 μl, 0.44 mmol) and 1-(phenylsulfanyl)pyrrolidine-2,5-dione 5a (90.9 mg, 0.44 mmol). Purification by flash column chromatography (PE/EtOAc = 8:2) afforded 2i (30 mg, 0.12 mmol, 26%) as a white solid. The spectral data are in agreement with the literature report. 4 mp: 30-33 C. IR (neat): ν max 3138, 3074, 3006, 2954, 1674, 1604, 1578, 1475, 1435, 1347, 1321, 1290, 1243, 1203, 1145, 1108, 1082, 1024 cm 1. 1 H NMR (CDCl 3, 400 MHz): δ 10.80 (s, 1H), 7.94 (dd, J = 2.4, 0.3 Hz, 1H), 7.46 (ddd, J = 8.7, 2.4, 0.4 Hz, 1H), 7.19-7.14 (m, 2H), 7.11-7.06 (m, 3H), 6.90 (dd, J = 8.7, 0.3 Hz, 1H), 3.85 (s, 3H). 13 C NMR (CDCl 3, 100 MHz): δ 170.1, 161.9, 141.5, 138.0, 135.7, 129.2 (2C), 128.5 (2C), 126.2, 123.5, 119.2, 113.4, 52.6. 4 Komeyama, K.; Aihara, K.; Kashihara, T.; Takaki, K. Chem. Lett. 2011, 40, 1254. 9

MS m/z (relative intensity): 260 (M +, 60), 229 (19), 228 (100), 172 (47), 171 (59), 139 (14), 128 (15), 95 (39), 86 (23), 85 (12), 77 (19), 69 (16), 65 (13), 63 (24), 53 (17), 51 (35). Methyl 2-hydroxy-5-(phenylsulfanyl)benzoate (2j) 1 Formula: C 16 H 12 OS Mw = 252.33 g. mol 1 Compound 2j was synthesized from 2-naphthol 1j (69.6 mg, 0.48 mmol) and 1-(phenylsulfanyl)pyrrolidine-2,5-dione 5a (100 mg, 0.48 mmol). Purification by flash column chromatography (PE/EtOAc = 98:2) afforded 2j (108 mg, 0.43 mmol, 89%) as a white solid. The spectral data are in agreement with the literature report. 1 mp: 69-71 C. IR (neat): ν max 3404, 3375, 3060, 2923, 1617, 1594, 1580, 1571, 1509, 1477, 1459, 1439, 1386, 1345, 1257, 1199, 1149, 1126, 1080, 1024 cm 1. 1 H NMR (CDCl 3, 400 MHz): δ 8.25 (d app, J = 8.5 Hz, 1H), 7.93 (d, J = 8.9 Hz, 1H), 7.84 (d app, J = 8.1 Hz, 1H), 7.52 (ddd, J = 8.4, 6.9, 1.3 Hz, 1H), 7.39 (ddd, J = 8.1, 6.9, 1.2 Hz, 1H), 7.37 (d, J = 8.9 Hz, 1H), 7.22-7.17 (m, 3H), 7.12 (m, 1H), 7.07-7.04 (m, 2H). 13 C NMR (CDCl 3, 100 MHz): δ 157.1, 135.6, 135.5, 133.0, 129.6, 129.3 (2C), 128.7, 128.1, 126.5 (2C), 126.0, 124.8, 124.0, 117.0, 108.1. MS m/z (relative intensity): 252 (M +, 100), 219 (15), 191 (20), 147 (23), 146 (52), 117 (10), 115 (17), 102 (15), 77 (10), 51 (11). 1,4-Bis(phenylsulfanyl)naphthalene (2k) 5 Formula: C 22 H 16 S 2 Mw = 344.49 g. mol 1 Compound 2k was synthesized from naphthalene 1k (62.5 mg, 0.48 mmol) and 1-(phenylsulfanyl)pyrrolidine-2,5-dione 5a (100 mg, 0.48 mmol). Purification by flash column chromatography (PE/EtOAc = 100:0 to 98:2) afforded 2k (29 mg, 0.08 mmol, 17%) as a white solid. The spectral data are in agreement with the literature report. 5 mp: 106-109 C. IR (neat): ν max 3067, 2958, 2924, 2853, 1725, 1578, 1494, 1475, 1438, 1356, 1252, 1072, 1026 cm 1. 1 H NMR (CDCl 3, 400 MHz): δ 8.44-8.39 (m, 2H), 7.58-7.53 (m, 2H), 7.43 (s, 2H), 7.28-7.19 (m, 10H). 5 Novi, M.; Garbarino, G.; Petrillo, G.; Dell Erba, C. Tetrahedron 1990, 46, 2205. 10

13 C NMR (CDCl 3, 100 MHz): δ 135.7 (2C), 133.6 (2C), 133.1 (2C), 130.8 (2C), 130.3 (4C), 129.4 (4C), 127.4 (2C), 127.0 (2C), 126.1 (2C). MS m/z (relative intensity): 344 (M +, 100), 236 (17), 235 (79), 234 (65), 221 (12), 203 (14), 202 (77), 189 (16), 158 (25), 114 (15), 78 (10), 77 (35), 65 (14), 51 (45). 1,3,5-Trimethyl-2-[(4-methylphenyl)sulfanyl]benzene (2m) 1 Formula: C 16 H 18 S Mw = 242.38 g. mol 1 Compound 2m was synthesized from 1,3,5-trimethylbenzene 1f (62 μl, 0.45 mmol) and 1-[(4-methylphenyl)sulfanyl]pyrrolidine-2,5-dione 5b (99.6 mg, 0.45 mmol). Purification by flash column chromatography (PE 100%) afforded 2m (99 mg, 0.41 mmol, 91%) as a white solid. The spectral data are in agreement with the literature report. 1 mp: 89-92 C. IR (neat): ν max 3024, 2920, 2858, 1602, 1492, 1461, 1401, 1374, 1182, 1104, 1089, 1059, 1036, 1015 cm 1. 1 H NMR (CDCl 3, 400 MHz): δ 7.03-6.99 (m, 4H), 6.85 (d app, J = 8.2 Hz, 2H), 2.42 (s, 6H), 2.34 (s, 3H), 2.29 (s, 3H). 13 C NMR (CDCl 3, 100 MHz): δ 143.8 (2C), 139.2, 134.9, 134.3, 129.8 (2C), 129.4 (2C), 127.6, 125.8 (2C), 21.9 (2C), 21.3, 21.0. MS m/z (relative intensity): 242 (M +, 100), 150 (70), 149 (29), 135 (17), 119 (25), 117 (11), 115 (18), 106 (12), 105 (31), 103 (12), 91 (58), 79 (12), 78 (12), 77 (32), 65 (25), 51 (14). 1,3,5-Trimethoxy-2-[(4-methylphenyl)sulfanyl]benzene (2n) 6 Formula: C 16 H 18 O 3 S Mw = 290.38 g. mol 1 Compound 2n was synthesized from 1,3,5-trimethoxybenzene 1g (75 mg, 0.44 mmol) and 1-[(4-methylphenyl)sulfanyl]pyrrolidine-2,5-dione 5b (97.7 mg, 0.44 mmol). Purification by flash column chromatography (PE/EtOAc = 95:5) afforded 2n (83 mg, 0.29 mmol, 65%) as a white solid. The spectral data are in agreement with the literature report. 6 mp: 120-122 C. IR (neat): ν max 3006, 2991, 2964, 2923, 2835, 1582, 1490, 1470, 1451, 1435, 1411, 1336, 1224, 1207, 1163, 1121, 1096, 1084, 1044, 1032, 1015 cm 1. 1 H NMR (CDCl 3, 400 MHz): δ 6.99-6.93 (m, 4H), 6.21 (s, 2H), 3.86 (s, 3H), 3.80 (s, 6H), 2.25 (s, 3H). 13 C NMR (CDCl 3, 100 MHz): δ 162.9, 162.6 (2C), 135.1, 134.2, 129.4 (2C), 126.1 (2C), 99.4, 91.3 (2C), 56.4 (2C), 55.5, 21.0. 6 Zhang, M.; Zhang, S.; Pan, C.; Chen, F. Synth. Commun. 2012, 42, 2844. 11

MS m/z (relative intensity): 290 (M +, 100), 244 (15), 242 (17), 215 (11), 129 (11), 105 (21), 69 (14). 2-[(4-Methoxyphenyl)sulfanyl]-1,3,5-trimethylbenzene (2o) 1 Formula: C 16 H 18 OS Mw = 258.38 g. mol 1 Compound 2o was synthesized from 1,3,5-trimethylbenzene 1f (62 μl, 0.45 mmol) and 1-[(4-methoxyphenyl)sulfanyl]pyrrolidine-2,5-dione 5c (106.8 mg, 0.45 mmol). Purification by flash column chromatography (PE/EtOAc = 100:0 to 98:2) afforded 2o (101 mg, 0.39 mmol, 87%) as a white solid. The spectral data are in agreement with the literature report. 1 mp: 69-71 C. IR (neat): ν max 3017, 2959, 2913, 2836, 1592, 1572, 1490, 1457, 1436, 1286, 1237, 1175, 1033 cm 1. 1 H NMR (CDCl 3, 400 MHz): δ 6.99 (dd app, J = 1.2, 0.6 Hz, 2H), 6.93-6.89 (m, 2H), 6.78-6.74 (m, 2H), 3.75 (s, 3H), 2.40 (s, 6H), 2.31 (s, 3H). 13 C NMR (CDCl 3, 100 MHz): δ 157.5, 143.5 (2C), 139.0, 129.4 (2C), 129.1, 128.5, 127.8 (2C), 114.8 (2C), 55.4, 21.9 (2C), 21.2. MS m/z (relative intensity): 258 (M +, 92), 243 (12), 151 (15), 150 (100), 149 (38), 135 (20), 119 (12), 115 (18), 105 (15), 91 (49), 78 (15), 77 (34), 65 (20), 63 (13), 53 (14), 51 (14). 1,3,5-Trimethoxy-2-[(4-methoxyphenyl)sulfanyl]benzene (2p) Formula: C 16 H 18 O 4 S Mw = 306.38 g. mol 1 Compound 2p was synthesized from 1,3,5-trimethoxybenzene 1g (75 mg, 0.44 mmol) and 1-[(4-methoxyphenyl)sulfanyl]pyrrolidine-2,5-dione 5c (104.7 mg, 0.44 mmol). Purification by flash column chromatography (PE/EtOAc = 9:1 to 8:2) afforded 2p (82 mg, 0.27 mmol, 61%) as a pale yellow solid. mp: 86-89 C. IR (neat): ν max 3001, 2926, 2835, 1582, 1492, 1469, 1451, 1411, 1335, 1286, 1243, 1223, 1206, 1178, 1162, 1119, 1030 cm 1. 1 H NMR (CDCl 3, 400 MHz): δ 7.06 (d app, J = 9.0 Hz, 2H), 6.73 (d app, J = 9.0 Hz, 2H), 6.19 (s, 2H), 3.85 (s, 3H), 3.81 (s, 6H), 3.73 (s, 3H). 13 C NMR (CDCl 3, 100 MHz): δ 162.7, 162.4 (2C), 157.7, 129.3, 128.7 (2C), 114.4 (2C), 100.7, 91.3 (2C), 56.4 (2C), 55.5, 55.4. MS m/z (relative intensity): 306 (M +, 100), 260 (15), 258 (18), 231 (11), 198 (16), 139 (12), 137 (25), 130 (11), 121 (27), 109 (14), 95 (13), 77 (16), 69 (34), 63 (15), 59 (19), 53 (16). HRMS: calcd for C 16 H 19 O 4 S (M+H) + : 307.0999, found : 307.0998. 12

2-[(4-Bromophenyl)sulfanyl]-1,3,5-trimethylbenzene (2q) 1 Formula: C 15 H 15 BrS Mw = 307.25 g. mol 1 Compound 2q was synthesized from 1,3,5-trimethylbenzene 1f (25 μl, 0.18 mmol) and 1-[(4-bromophenyl)sulfanyl]pyrrolidine-2,5-dione 5d (51.4 mg, 0.18 mmol). Purification by flash column chromatography (PE 100%) afforded 2q (53 mg, 0.17 mmol, 96%) as a white solid. The spectral data are in agreement with the literature report. 1 mp: 102-104 C. IR (neat): ν max 2953, 2920, 2851, 1600, 1560, 1469, 1386, 1372, 1177, 1086, 1068, 1032, 1004 cm 1. 1 H NMR (CDCl 3, 400 MHz): δ 7.28 (d app, J = 8.8 Hz, 2H), 7.02 (d app, J = 0.6 Hz, 2H) 6.78 (d app, J = 8.8 Hz, 2H), 2.37 (s, 6H), 2.33 (s, 3H). 13 C NMR (CDCl 3, 100 MHz): δ 143.8 (2C), 139.8, 137.9, 132.0 (2C), 129.6 (2C), 127.1 (2C), 126.5, 118.1, 21.8 (2C), 21.3. MS m/z (relative intensity): 308 (M +, 68), 306 (M +, 68), 225 (18), 212 (30), 194 (19), 179 (24), 150 (92), 149 (40), 135 (25), 119 (46), 117 (29), 115 (37), 114 (31), 108 (22), 106 (34), 105 (51), 103 (27), 92 (22), 91 (100), 79 (21), 78 (24), 77 (68), 76 (20), 65 (35), 63 (22), 53 (21), 51 (33), 50 (27). 2-[(4-Bromophenyl)sulfanyl]-1,3,5-trimethoxybenzene (2r) 6 Formula: C 15 H 15 BrO 3 S Mw = 355.25 g. mol 1 Compound 2r was synthesized from 1,3,5-trimethoxybenzene 1g (75 mg, 0.44 mmol) and 1-[(4-bromophenyl)sulfanyl]pyrrolidine-2,5-dione 5d (126.3 mg, 0.44 mmol). Purification by flash column chromatography (PE/EtOAc = 95:5) afforded 2r (112 mg, 0.32 mmol, 71%) as a white solid. The spectral data are in agreement with the literature report. 6 mp: 128-131 C. IR (neat): ν max 2950, 2928, 2836, 1587, 1578, 1469, 1457, 1407, 1340, 1223, 1204, 1189, 1158, 1123, 1093, 1082, 1067, 1036, 1006 cm 1. 1 H NMR (CDCl 3, 400 MHz): δ 7.25 (d app, J = 8.5 Hz, 2H), 6.88 (d app, J = 8.5 Hz, 2H), 6.21 (s, 2H), 3.87 (s, 3H), 3.80 (s, 6H). 13 C NMR (CDCl 3, 100 MHz): δ 163.3, 162.5 (2C), 138.2, 131.5 (2C), 127.3 (2C), 117.9, 98.2, 91.3 (2C), 56.4 (2C), 55.6. MS m/z (relative intensity): 356 (M +, 100), 354 (M +, 100), 260 (34), 245 (18), 242 (43), 141 (19), 137 (19), 130 (29), 122 (20), 109 (24), 108 (16), 75 (22), 69 (44), 59 (20), 53 (16). 13

1,3,5-Trimethoxy-2-[(4-nitrophenyl)sulfanyl]benzene (2t) 1 Formula: C 15 H 15 NO 5 S Mw = 321.35 g. mol 1 Compound 2t was synthesized from 1,3,5-trimethoxybenzene 1g (84.9 mg, 0.50 mmol) and 1-[(4-nitrophenyl)sulfanyl]pyrrolidine-2,5-dione 5e (126.1 mg, 0.50 mmol). Purification by flash column chromatography (PE/EtOAc = 8:2) afforded 2t (75 mg, 0.23 mmol, 47%) as a yellow solid. The spectral data are in agreement with the literature report. 1 mp: 131-133 C. IR (neat): ν max 3098, 3007, 2943, 2843, 1594, 1579, 1510, 1469, 1458, 1414, 1332, 1229, 1208, 1163, 1125, 1097, 1034 cm 1. 1 H NMR (CDCl 3, 400 MHz): δ 8.00 (d app, J = 9.1 Hz, 2H), 7.05 (d app, J = 9.1 Hz, 2H), 6.24 (s, 2H), 3.89 (s, 3H), 3.81 (s, 6H). 13 C NMR (CDCl 3, 100 MHz): δ 163.9, 162.5 (2C), 149.6, 144.7, 124.9 (2C), 123.8 (2C), 96.0, 91.4 (2C), 56.4 (2C), 55.7. MS m/z (relative intensity): 321 (M +, 100), 275 (18), 246 (8), 242 (12), 141 (9), 109 (9), 69 (16). 2-(Ethylsulfanyl)-1,3,5-trimethylbenzene (2u) 7 Formula: C 11 H 16 S Mw = 180.31 g. mol 1 Compound 2u was synthesized from 1,3,5-trimethylbenzene 1f (62 μl, 0.45 mmol) and 1-(ethylsulfanyl)pyrrolidine-2,5-dione 5f (71.6 mg, 0.45 mmol). Purification by flash column chromatography (PE 100%) afforded 2u (33 mg, 0.18 mmol, 41%) as a clear oil. The spectral data are in agreement with the literature report. 7 IR (neat): ν max 3022, 2961, 2923, 2855, 1726, 1603, 1567, 1455, 1374, 1260, 1059, 1031 cm 1. 1 H NMR (CDCl 3, 400 MHz): δ 6.94 (dd app, J = 1.2, 0.6 Hz, 2H), 2.66 (q, J = 7.4 Hz, 2H), 2.51 (s, 6H), 2.27 (s, 3H), 1.18 (t, J = 7.4 Hz, 3H). 13 C NMR (CDCl 3, 100 MHz): δ 143.2 (2C), 138.0, 130.1, 129.0 (2C), 29.5, 22.1 (2C), 21.1, 15.0. MS m/z (relative intensity): 180 (M +, 100), 152 (25), 151 (89), 120 (12), 119 (56), 117 (12), 115 (17), 107 (42), 105 (46), 103 (11), 91 (45), 79 (14), 77 (26), 65 (17), 59 (17), 53 (10), 51 (14). 2-(Ethylsulfanyl)-1,3,5-trimethoxybenzene (2v) Formula: C 11 H 16 O 3 S Mw = 228.31 g. mol 1 7 Nakayama, J.; Fujita, T.; Hoshino, M. Chem. Lett. 1983, 2, 249. 14

Compound 2v was synthesized from 1,3,5-trimethoxybenzene 1g (75 mg, 0.44 mmol) and 1-(ethylsulfanyl)pyrrolidine-2,5-dione 5f (70.3 mg, 0.44 mmol). Purification by flash column chromatography (PE/EtOAc = 95:5) afforded 2v (72 mg, 0.32 mmol, 71%) as a white solid. mp: 56-58 C. IR (neat): ν max 2998, 2960, 2927, 2837, 1578, 1454, 1434, 1408, 1334, 1224, 1204, 1158, 1118, 1091, 1035 cm 1. 1 H NMR (CDCl 3, 400 MHz): δ 6.14 (s, 2H), 3.85 (s, 6H), 3.81 (s, 3H), 2.72 (q, J = 7.4 Hz, 2H), 1.13 (t, J = 7.4 Hz, 3H). 13 C NMR (CDCl 3, 100 MHz): δ 162.2 (2C), 161.6, 101.6, 91.0 (2C), 56.2 (2C), 55.4, 28.5, 14.6. MS m/z (relative intensity): 228 (M +, 100), 200 (13), 199 (50), 184 (20), 171 (36), 139 (19), 125 (23), 111 (13), 109 (13), 96 (11), 95 (15), 85 (11), 75 (11), 69 (38), 59 (16), 53 (15). HRMS: calcd for C 11 H 17 O 3 S (M+H) + : 229.0893, found : 229.0895. 5. References [1] Saravanan, P.; Anbarasan, P. Org. Lett. 2014, 16, 848. [2] Savarin, S.; Srogl, J.; Liebeskind, L. S. Org. Lett. 2002, 4, 4309. [3] Abe, Y.; Nakabayashi, T.; Tsurugi, J. Bull. Chem. Soc. Jpn. 1973, 46, 1898. [4] Komeyama, K.; Aihara, K.; Kashihara, T.; Takaki, K. Chem. Lett. 2011, 40, 1254. [5] Novi, M.; Garbarino, G.; Petrillo, G.; Dell Erba, C. Tetrahedron 1990, 46, 2205. [6] Zhang, M.; Zhang, S.; Pan, C.; Chen, F. Synth. Commun. 2012, 42, 2844. [7] Nakayama, J.; Fujita, T.; Hoshino, M. Chem. Lett. 1983, 2, 249. 15

6. 1 H and 13 C NMR spectra of N-thiosuccinimides (5a-5f) 16

7. 1 H and 13 C NMR spectra of thioarenes (2a-2v) 29