TfOH-Catalyzed Reaction between 3-Diazoindolin-2-imines and

Nov 10, 2017 - The C3-aryl indole skeleton is a privileged structure in various natural indole alkaloids and most of them are biologically active (Fig...
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TfOH-Catalyzed Reaction between 3‑Diazoindolin-2-imines and Electron-Rich Arenes: Access to 3‑Aryl-2-aminoindoles Jie Qi, Zaibin Wang, Bo Lang, Ping Lu,* and Yanguang Wang* Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China S Supporting Information *

ABSTRACT: TfOH-catalyzed reactions between 3-diazoindolin-2-imines and electron-rich arenes were disclosed. These metal-free reactions furnished 3-aryl-2-aminoindoles in moderate to excellent yields with the tolerance of a broad range of functional groups.

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one example was demonstrated in Wang’s report.9 3-Diazo-2oxoindole functioned as Lewis base and combined with boroxine which triggered the subsequent migration of aryl to the C3-position of indole. Alternatively, Hu disclosed a Brønsted acid catalyzed reaction between electron-rich arenes and 3-diazo-2-oxoindoles which provided 3-aryl-2-oxindoles in excellent yields.10 In this case, a sequence of protonation of 3diazo-2-oxoindoles and followed by Friedel−Crafts alkylation of arene was proposed. The scope of arene was confined to electron-rich benzene and thiophene. In 2014, we reported the synthesis of 3-diazoindolin-2imines11 and used them for the study of the chemistry of αamidino rhodium carbene. Thus, a series of rhodium catalyzed reactions had been carried out and a number of indolecontaining compounds were synthesized.12 Following this step, reactions via α-amidino copper carbene13 and α-amidino palladium carbene14 had also been realized. Besides these metal catalyzed reactions, we also observed the electrophilicity of 3-diazoindolin-2-imines through the reaction with nucleophiles in the presence of base, such as naphathlenols and 2phenylacetates. In this way, azo dyes were prepared and the nitrogen was survived.15 In order to extend the reaction types of 3-diazoindolin-2-imines, we hereby tried the reaction between 3-diazoindolin-2-imines and electron-rich arenes in the presence of Brønsted acid. 3-Aryl-2-aminoindoles were obtained in moderate to excellent yields.

INTRODUCTION The C3-aryl indole skeleton is a privileged structure in various natural indole alkaloids and most of them are biologically active (Figure 1).1 Besides those, it also plays an important role in

Figure 1. Pharmacologically active indole alkaloids based on C3-aryl indole skeleton.

drug discovery.2 By surfing the literature, palladium catalyzed intramolecular or intermolecular coupling reactions3 have been indicated to be the main strategy in the construction of C3-aryl indole skeleton. Other metals, such as iron,4 copper,5 nickel,6 and scandium,7 are also found to be effective in the preparation of them. Although these methods provide simple and convenient way, more and more chemists are interested in developing transition metal-free methods because of the price of the transition metal and unfriendly damage to the environment. Therefore, transition metal-free oxidative crosscoupling of C−H bonds has become a straightforward and atom-economical approach for the construction of C−C bonds. In 2016, Kumar’s group developed a base promoted dehydrogenative cross coupling between 2-oxindoles and nitrobenzenes to synthesize 3-aryl-2-oxindoles by applying DMSO as oxidant. 8 In this transformation, aromatic nucleophilic substitution (SNAr) is postulated to be the key step which confined the scope of arene to the electron-deficient arene. Arylation of 3-diazo-2-oxoindole with arylboroxine in the presence of base could also afford 3-aryl-2-oxoindole, but only © 2017 American Chemical Society

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RESULTS AND DISCUSSION To begin with, we conducted a trial between 3-diazoindolin-2imine (1a) and 2,5-dimethylthiophene (2a, 5 equiv) in the presence of TfOH (0.5 equiv) in chloroform at 35 °C for 30 min. To our delight, the arylated product 3a was isolated in Received: September 25, 2017 Published: November 10, 2017 12640

DOI: 10.1021/acs.joc.7b02423 J. Org. Chem. 2017, 82, 12640−12646

Article

The Journal of Organic Chemistry Table 1. Optimization of Reaction Conditionsa

a

entry

catalyst (equiv)

solvent

equiv of 2a

time (min)

yield (%)b

1 2 3 4 5 6 7 8 9 10 11 12 13 14

TfOH (0.5) MsOH (0.5) TsOH (0.5) PhSO3H (0.5) none TfOH (0.2) TfOH (0.8) TfOH (0.5) TfOH (0.5) TfOH (0.5) TfOH (0.5) TfOH (0.5) TfOH (0.4) TfOH (0.3)

CHCl3 CHCl3 CHCl3 CHCl3 CHCl3 CHCl3 CHCl3 DCE DCM DCE DCE DCE DCE DCE

5 5 5 5 5 5 5 5 5 2 5 5 5 5

30 30 30 30 30 30 30 30 30 30 15 45 30 30

88 trace 43 49 NR 81 88 95 93 74 67 95 83 81

Reaction conditions: 1a (0.2 mmol), 2a, catalyst, solvent (2 mL), 35 °C. bIsolated yield.

88% yield (Table 1, entry 1). Structure of 3a was unequivocally confirmed by single crystal analysis of its analogue 3o.16 Inspired by this result, the reaction conditions were evaluated. Other Brønsted acids, such as MsOH, TsOH, and benzenesulfonic acid, gave no better results than TfOH did (Table 1, entry 2−4). Without catalyst, 3a could not be detected by thin layer chromatography (TLC) with the recovery of the starting materials (Table 1, entry 5). Furthermore, either decreasing or increasing the loading amount of catalyst would not give a higher yield (Table 1, entry 6−7). After screening other solvents, 1,2-dichloroethane (DCE) was found to be the best solvent in comparison to chloroform and dichloromethane (DCM) (Table 1, entries 8 and 9). In the cases where DCE was used as solvent, reducing the amount of 2a to 2 equiv offered a moderate yield (Table 1, entry 10). Shortening or extending the reaction time (Table 1, entries 11 and 12) and decreasing the amount of TsOH (Table 1, entries 13 and14) also led to a decrease in the yield. It is worthwhile to note that all the reactions were conducted under air atmosphere in AR-grade solvents, which makes this transformation applicable and maneuverable. With the optimized reaction conditions in hand (Table 1, entry 8), we turned to evaluate the substrate diversity and summarize the limitations of the reaction. First of all, we examined the scope of 3-diazoindolin-2-imines 1 as they reacted with 2a. As shown in Scheme 1, substituent on the 1position of the indole ring could be altered to alkyl and aryl groups, such as methyl, ethyl, allyl, and benzyl. Thus, the corresponding products 3b−e were obtained in 75−98% yields. With the electron-withdrawing groups (F, Cl, Br) occupying the 5-position of indoles, the corresponding products 3h−j were afforded in 96−98% yields, which is higher than those with an electron-donating group (3f, g). The sulfonyl group could either be arenesulfonyl (3a, 3k−m) or alkanesulfonyl (3n), which indicated that the electronic and steric effects of the sulfonyl group did not give significant impact on the reaction outcome.

Scheme 1. TfOH-Catalyzed Reactions of 1 with Heterocycles 2

In parallel, a series of thiophenes was subjected to the reaction with 1a under the same conditions. As we can see from the Scheme 1, 2-methylthiophene (2b) and 3-methylthiophene (2c) provided the corresponding products 3o and 3p in 63 and 77% yields, respectively. With two methyl groups occupied on the 3,4-position of thiophene, the expected product 3q was afforded in 72% yield. Meanwhile, 2-methylbenzo[b]thiophene 12641

DOI: 10.1021/acs.joc.7b02423 J. Org. Chem. 2017, 82, 12640−12646

Article

The Journal of Organic Chemistry (2d) and 3-methylbenzo[b]thiophene (2e) could also be used as substrates and afforded 3r and 3s in 70 and 53% yields, respectively. Except for thiophene derivatives, pyrroles and indoles also worked well in this transformation. For example, 2,5-dimethyl-1H-pyrrole and 1,2-dimethyl-1H-indole afforded 3t and 3u in 90 and 53% yields, respectively. To further demonstrate the practicality and efficiency of the developed reaction, a scale-up reaction was performed. After adding the solution of TfOH (130 mg, 0.87 mmol) in DCE (7 mL) to the solution of 1a (1.50 g, 4.34 mmol) and 2a (2.43 g, 21.7 mmol) in DCE (43 mL) at 0 °C, the reaction mixture was stirred at room temperature for 30 min. In this way, 3a (1170 mg, 63% yield) was isolated by column chromatography. Subsequently, a series of arenes were examined (Scheme 2). It turned out that all of them gave satisfying outcomes,

Scheme 3. Plausible Mechanism of the Reaction

occurs to provide cation intermediate B. Finally, the FriedelCraft arylation of toluene with B happens and affords 3-aryl-2aminoindole 5a.

Scheme 2. TfOH-Catalyzed Reactions of 1e with Substituted Benzenes and Naphthalene

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CONCLUSION In conclusion, we developed a concise and practical approach to 3-aryl-2-aminoindoles from 3-diazoindolin-2-imines and electron-rich aromatic compounds in the presence of trifluoromethanesulfonic acid. Compared with the published methods for the synthesis of 3-aryl-2-aminoindoles,12a,13,14 this protocol is metal-free and the reaction conditions are much milder. Moreover, the reaction tolerated a broad range of electron-rich arenes, including thiophene, pyrrole, indole, substituted benzene, and naphthalene.

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EXPERIMENTAL SECTION

General Considerations. Melting points were measured with a micro melting point apparatus. 1H NMR spectra were obtained on 400 MHz in acetone-d6 or DMSO-d6. The chemical shifts were quoted in parts per million (ppm) referenced to the internal solvent signals (2.05 ppm for acetone-d6, 2.50 ppm for DMSO-d6). 13C NMR spectra were recorded on 100 MHz in acetone-d6 or DMSO-d6. The chemical shifts were reported in ppm referenced to the internal solvent signals (29.84 ppm for acetone-d6, 39.52 ppm for DMSO-d6). The following abbreviations were used to describe peak patterns where appropriate: b = broad, s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet. Coupling constants J, were reported in hertz unit (Hz). Infrared spectra were obtained on an FT-IR spectrometer. Highresolution mass spectra (HRMS) data were obtained on EI-TOF, ESI, or MALDI-TOF mass spectrometer. Flash column chromatography was performed employing 300−400 mesh silica gel. Thin layer chromatography (TLC) was performed on silica gel HSGF254. 3-Diazoindolin-2-imines were prepared using the published procedures,11a,b and other electron-rich arenes are commercially available. General Procedure for the Synthesis of 3. A 25 mL roundbottom flask was charged with 1 (0.2 mmol), 2 (1.0 mmol), TfOH (50 mol %), and DCE (2 mL). The mixture was stirred at 35 °C (oil bath) for 30 min. After cooling to room temperature, the resulted mixture was evaporated under reduced pressure and the residue was purified by flash column chromatography on a silica gel to give pure product 3. 4-Chloro-N-(3-(2,5-dimethylthiophen-3-yl)-1-methyl-1H-indol-2yl)benzenesulfonamide (3a). The product was purified by chromatography (ethyl acetate/petroleum ether = 1:6, v/v). White solid; Yield: 77 mg, 95%; mp 124.6−125.8 °C; 1H NMR (400 MHz, acetone-d6): δ 9.05 (s, 1H), 7.51 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.0 Hz, 1H), 7.34 (d, J = 8.4 Hz, 2H), 7.30−7.22 (m, 2H), 7.07 (dd, J1 = J2 = 7.4 Hz, 1H), 6.47 (s, 1H), 3.87 (s, 3H), 2.36 (s, 3H), 2.01 (s, 3H); 13 C NMR (100 MHz, acetone-d6): δ 139.8, 139.0, 136.0, 135.8, 133.1, 130.0, 129.4, 129.1, 128.6, 127.6, 126.2, 123.5, 121.0, 120.5, 110.8, 109.4, 29.7, 15.1, 14.6; IR (film): 3265, 3097, 3062, 2917, 1905, 1695,

although the ones with stronger electron-donating group usually reacted better. Starting with toluene, 5a was obtained in 73% yield with excellent regioselectivity. When o-, m-, and pxylene were used, corresponding products (5b, 5c, 5d) were obtained in 36, 95, and 45% yields, respectively. The substituent effect on this reaction is significant. When mesitylene was used, 5e was isolated in 94% yield. In alignment with the previous observations, arenes with stronger electrondonating groups showed better reactivity, such as anisole and 1,4-dimethoxybenzene, which afforded 5f and 5g in 89 and 98% yields, respectively. Except for the substituted benzenes, naphthalene showed the reactivity toward 3-diazoindolin-2imine. Thus, 5h was obtained in 72% yield with high regioselectivity. On the basis of the screening of the reaction conditions, it turns out that the acidity of the Brønsted acid is essential to the reaction. Referenced to Hu’s reports on the arylation of diazo compounds17 and Mascarelli’s postulated phenyl cation intermediate which forms from the decomposition of an arenediazonium salt,18 we propose a possible mechanism (Scheme 3). First, the protonation of 3-diazoindolin-2-imine 1e results in the formation of a diazonium salt A, which is stabilized by conjugation with phenyl. Then, denitrogenation 12642

DOI: 10.1021/acs.joc.7b02423 J. Org. Chem. 2017, 82, 12640−12646

Article

The Journal of Organic Chemistry 1616, 1585, 1474, 1322 cm −1 ; HRMS (EI): M + calcd for C21H19ClN2O2S2 430.0576; found 430.0573. N-(3-(2,5-Dimethylthiophen-3-yl)-1-methyl-1H-indol-2-yl)-4methylbenzenesulfonamide (3b). The product was purified by chromatography (ethyl acetate/petroleum ether = 1:6, v/v). White solid; Yield: 52 mg, 75%; m.p.105.8−107.2 °C; 1H NMR (400 MHz, acetone-d6): δ 8.82 (s, 1H), 7.48−7.38 (m, 3H), 7.29−7.20 (m, 2H), 7.13 (d, J = 8.4 Hz, 2H), 7.05 (dd, J1 = J2 = 7.6 Hz, 1H), 6.44 (s, 1H), 3.84 (s, 3H), 2.39 (s, 3H), 2.34 (s, 3H), 1.96 (s, 3H); 13C NMR (100 MHz, acetone-d6): δ 143.8, 138.4, 135.8, 135.6, 133.2, 130.2, 129.8, 128.7, 128.3, 127.5, 126.4, 123.3, 121.0, 120.5, 110.8, 109.3, 29.8, 21.6, 15.2, 14.7; IR (film): 3257, 3058, 2917, 2857, 2249, 1723, 1694, 1616, 1470, 1434 cm−1; HRMS (EI): M+ calcd for C22H22N2O2S2 410.1123; found 410.1121. N-(3-(2,5-Dimethylthiophen-3-yl)-1-ethyl-1H-indol-2-yl)-4-methylbenzenesulfonamide (3c). The product was purified by chromatography (ethyl acetate/petroleum ether = 1:6, v/v). White solid; yield: 83 mg, 98%; mp 153.8−154.6 °C; 1H NMR (400 MHz, acetone-d6): δ 8.83 (s, 1H), 7.48 (d, J = 8.4 Hz, 1H), 7.41 (d, J = 8.0 Hz, 2H), 7.29− 7.20 (m, 2H), 7.11 (d, J = 8.0 Hz, 2H), 7.05 (dd, J1 = J2 = 7.6 Hz, 1H), 6.48 (s, 1H), 4.45 (q, J = 6.8 Hz, 2H), 2.38 (s, 3H), 2.33 (s, 3H), 1.97 (s, 3H), 1.44 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, acetone-d6): δ 143.7, 138.4, 135.6, 134.7, 133.1, 130.2, 129.7, 128.6, 127.5, 127.4, 126.6, 123.3, 121.1, 120.3, 111.0, 109.5, 38.1, 21.6, 15.2, 15.1, 14.7; IR (film): 3258, 3052, 2974, 2852, 2731, 1910, 1719, 1694, 1615, 1597 cm−1; HRMS (EI): M+ calcd for C23H24N2O2S2 424.1279; found 424.1277. N-(1-Allyl-3-(2,5-dimethylthiophen-3-yl)-1H-indol-2-yl)-4-methylbenzenesulfonamide (3d). The product was purified by chromatography (ethyl acetate/petroleum ether = 1:6, v/v). White solid; yield: 88 mg, 96%; mp 175.7−177.3 °C; 1H NMR (400 MHz, acetone-d6): δ 8.85 (s, 1H), 7.47−7.38 (m, 3H), 7.27 (d, J = 7.6 Hz, 1H), 7.21 (dd, J1 = J2 = 7.2 Hz, 1H), 7.12 (d, J = 8.0 Hz, 2H), 7.05 (dd, J1 = J2 = 7.4 Hz, 1H), 6.48 (s, 1H), 6.08 (m, 1H), 5.19−4.96 (m, 4H), 2.38 (s, 3H), 2.34 (s, 3H), 1.97 (s, 3H); 13C NMR (100 MHz, acetone-d6): δ 143.7, 138.3, 135.7, 135.3, 135.1, 133.3, 130.0, 129.7, 128.6, 127.7, 127.4, 126.6, 123.3, 121.0, 120.5, 116.8, 111.4, 109.7, 45.9,21.6, 15.1, 14.7; IR (film): 3252, 3055, 2955, 2919, 2856, 2735, 2579, 2304, 1912, 1716 cm−1; HRMS (EI): M+ calcd for C24H24N2O2S2 436.1279; found 436.1280. N-(1-Benzyl-3-(2,5-dimethylthiophen-3-yl)-1H-indol-2-yl)-4methylbenzenesulfonamide (3e). The product was purified by chromatography (ethyl acetate/petroleum ether = 1:6, v/v). White solid; yield: 94 mg, 97%; mp 181.7−182.9 °C; 1H NMR (400 MHz, acetone-d6): δ 8.98 (s, 1H), 7.43 (d, J = 8.0 Hz, 2H), 7.35 (d, J = 8.4 Hz, 1H), 7.31−7.20 (m, 4H), 7.19−7.11 (m, 5H), 7.05 (dd, J1 = J2 = 7.6 Hz, 1H), 6.54 (s, 1H), 5.69 (s, 2H), 2.39 (s, 3H), 2.34 (s, 3H), 1.99 (s, 3H); 13C NMR (100 MHz, acetone-d6): δ 143.8, 139.2, 138.3, 135.7, 135.3, 133.4, 130.0, 129.8, 129.3, 128.7, 128.2, 127.9, 127.5, 127.4, 126.7, 123.5, 121.1, 120.6, 111.6, 110.0, 46.8, 21.6, 15.1, 14.7; IR (film): 3251, 3062, 3031, 2917, 2858, 2735, 2576, 2254, 1911, 1724 cm−1; HRMS (EI): M+ calcd for C28H26N2O2S2 486.1436; found 486.1440. N-(3-(2,5-Dimethylthiophen-3-yl)-1,5-dimethyl-1H-indol-2-yl)-4methylbenzenesulfonamide (3f). The product was purified by chromatography (ethyl acetate/petroleum ether = 1:6, v/v). White solid; yield: 78 mg, 92%; mp 177.8−178.7 °C; 1H NMR (400 MHz, acetone-d6): δ 8.78 (s, 1H), 7.40 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.4 Hz, 1H), 7.11 (d, J = 8.0 Hz, 2H), 7.07 (d, J = 8.4 Hz, 2H), 6.42 (s, 1H), 3.81 (s, 3H), 2.37 (s, 3H), 2.36 (s, 3H), 2.33 (s, 3H), 1.96 (s, 3H); 13C NMR (100 MHz, acetone-d6): δ 143.7, 138.3, 135.4, 134.2, 133.0, 130.3, 129.7, 129.4, 128.7, 128.1, 127.4, 126.5, 124.9, 120.4, 110.5, 108.7, 29.8, 21.6, 21.6, 15.1, 14.6; IR (film): 3253, 3030, 2917, 2859, 2734, 2254, 1908, 1724, 1700, 1596 cm−1; HRMS (EI): M+ calcd for C23H24N2O2S2 424.1279; found 424.1277. N-(3-(2,5-Dimethylthiophen-3-yl)-5-methoxy-1-methyl-1H-indol2-yl)-4-methylbenzenesulfonamide (3g). The product was purified by chromatography (ethyl acetate/petroleum ether = 1:6, v/v). White solid; yield: 57 mg, 65%; mp 89.3−90.2 °C; 1H NMR (400 MHz, acetone-d6): δ 8.79 (s, 1H), 7.40 (dd, J = 8.0, 0.8 Hz, 2H), 7.34 (dd, J

= 8.8, 1.2 Hz, 1H), 7.11 (d, J = 8.0 Hz, 2H), 6.94−6.84 (m, 1H), 6.71 (s, 1H), 6.45 (s, 1H), 3.81 (s, 3H), 3.71 (s, 3H), 2.37 (s, 3H), 2.33 (s, 3H), 1.97 (s, 3H); 13C NMR (100 MHz, acetone-d6): δ 155.4, 143.8, 138.4, 135.7, 133.1, 131.0, 130.4, 129.8, 128.7, 128.5, 127.5, 126.6, 113.8, 111.8, 109.0, 102.3, 55.9, 30.0, 21.7, 15.2, 14.8; IR (film): 3257, 3062, 2951, 2917, 2858,2832, 2735, 2585, 2254, 2108, 1913 cm−1; HRMS (EI): M+ calcd for C23H24N2O3S2 440.1228; found 440.1231. N-(3-(2,5-Dimethylthiophen-3-yl)-5-fluoro-1-methyl-1H-indol-2yl)-4-methylbenzenesulfonamide (3h). The product was purified by chromatography (ethyl acetate/petroleum ether = 1:6, v/v). White solid; Isolated yield: 82 mg, 96%; mp 95.3−97.2 °C; 1H NMR (400 MHz, acetone-d6): δ 8.91 (s, 1H), 7.48−7.38 (m, 3H), 7.12 (d, J = 8.0 Hz, 2H), 7.05 (td, J = 9.2, 2.4 Hz, 1H), 6.94 (dd, J = 9.6, 2.4 Hz, 1H), 6.44 (s, 1H), 3.85 (s, 3H), 2.37 (s, 3H), 2.33 (s, 3H), 1.97 (s, 3H); 13C NMR (100 MHz, acetone-d6): δ 158.7 (d, J = 232.2 Hz), 143.9, 138.2, 135.8, 133.4, 132.3, 129.85, 129.78, 129.6, 128.4, 127.4, 126.5 (d, J = 9.7 Hz), 112.0 (d, J = 9.5 Hz), 111.5 (d, J = 26.2 Hz), 109.3 (d, J = 4.7 Hz), 105.3 (d, J = 23.6 Hz), 30.1, 21.6, 15.1, 14.6; IR (film): 3257, 3067, 2918, 2856, 2249, 1729, 1659, 1626, 1597, 1486 cm−1; HRMS (EI): M+ calcd for C22H21FN2O2S2 428.1028; found 428.1029. N-(5-Chloro-3-(2,5-dimethylthiophen-3-yl)-1-methyl-1H-indol-2yl)-4-methylbenzenesulfonamide (3i). The product was purified by chromatography (ethyl acetate/petroleum ether = 1:6, v/v). White solid; yield: 87 mg, 98%; mp 175.7−177.3 °C; 1H NMR (400 MHz, acetone-d6): δ 8.91 (s, 1H), 7.50−7.44 (m, 1H), 7.41 (d, J = 8.0 Hz, 2H), 7.26−7.19 (m, 2H), 7.13 (d, J = 8.0 Hz, 2H), 6.41 (s, 1H), 3.85 (s, 3H), 2.38 (s, 3H), 2.33 (s, 3H), 1.97 (s, 3H); 13C NMR (100 MHz, acetone-d6): δ 144.0, 138.2, 135.9, 134.1, 133.6, 129.8, 129.3, 128.5, 127.4, 127.3, 125.8, 123.4, 119.9, 112.4, 109.0, 30.1, 21.6, 15.1, 14.6; IR (film): 3257, 3062, 2918, 2857, 2731, 2585, 2254, 1912, 1721, 1694 cm−1; HRMS (EI): M+ calcd for C22H21ClN2O2S2 444.0733; found 444.0736. N-(5-Bromo-3-(2,5-dimethylthiophen-3-yl)-1-methyl-1H-indol-2yl)-4-methylbenzenesulfonamide (3j). The product was purified by chromatography (ethyl acetate/petroleum ether = 1:6, v/v). White solid; yield: 96 mg, 98%; mp 116.5−118.2 °C; 1H NMR (400 MHz, acetone-d6): δ 8.91 (s, 1H), 7.45−7.32 (m, 5H), 7.13 (d, J = 8.4 Hz, 2H), 6.40 (s, 1H), 3.84 (s, 3H), 2.38 (s, 3H), 2.33 (s, 3H), 1.97 (s, 3H); 13C NMR (100 MHz, acetone-d6): δ 144.0, 138.2, 136.0, 134.4, 133.6, 129.8, 129.7, 129.3, 128.4, 128.0, 127.4, 125.9, 123.0, 113.3, 112.9, 108.9, 30.0, 21.6, 15.1, 14.6; IR (film): 3253, 3013, 2917, 2865, 1721, 1694, 1597, 1543, 1472 cm−1; HRMS (EI): M+ calcd for C22H21BrN2O2S2 488.0228; found 488.0229. N-(3-(2,5-Dimethylthiophen-3-yl)-1-methyl-1H-indol-2-yl)benzenesulfonamide (3k). The product was purified by chromatography (ethyl acetate/petroleum ether = 1:6, v/v). White solid; yield = 89%; mp 158.3−159.8 °C; 1H NMR (400 MHz, acetone-d6): δ 8.92 (s, 1H), 7.55 (dd, J = 8.4, 1.2 Hz, 2H), 7.53−7.46 (m, 1H), 7.36−7.32 (m, 2H), 7.34 (t, J = 7.6 Hz, 2H), 7.30−7.21 (m, 2H), 7.10−7.02 (m, 1H), 6.41 (s, 1H), 3.84 (s, 3H), 2.32 (s, 3H), 1.99 (s, 3H); 13C NMR (100 MHz, acetone-d6): δ 141.4, 135.8, 135.5, 133.4, 133.2, 130.1, 129.2, 128.7, 128.1, 127.4, 126.4, 123.3, 120.8, 120.4, 110.7, 109.4, 29.8, 15.1, 14.5; IR (film): 3583, 3257, 3059, 2916, 2857, 2735, 2254, 1891, 1724, 1694 cm−1; HRMS (EI): M+ calcd for C21H20N2O2S2 396.0966; found 396.0970. N-(3-(2,5-Dimethylthiophen-3-yl)-1-methyl-1H-indol-2-yl)-4fluorobenzenesulfonamide(3l). The product was purified by chromatography (ethyl acetate/petroleum ether = 1:6, v/v). White solid; yield: 68 mg, 82%; mp 108.3−109.2 °C; 1H NMR (400 MHz, acetone-d6): δ 8.98 (s, 1H), 7.64−7.54 (m, 2H), 7.45 (d, J = 8.0 Hz, 1H), 7.30−7.21 (m, 2H), 7.14−7.01 (m, 3H), 6.45 (s, 1H), 3.86 (s, 3H), 2.35 (s, 3H), 2.02 (s, 3H); 13C NMR (100 MHz, acetone-d6): δ 165.6 (d, J = 249.9 Hz), 137.6 (d, J = 3.1 Hz), 135.9, 133.2, 130.4 (d, J = 9.7 Hz), 130.2, 128.7, 127.9, 126.3, 123.5, 120.5, 120.1, 116.3 (d, J = 22.8 Hz), 110.8, 109.4, 29.8, 15.0, 14.6; IR (film): 3563, 3264, 3019, 2917, 1932, 1727, 1694, 1613, 1591 cm−1; HRMS (EI): M+ calcd for C21H19FN2O2S2 414.0872; found 414.0876. N-(3-(2,5-Dimethylthiophen-3-yl)-1-methyl-1H-indol-2-yl)-4nitrobenzenesulfonamide(3m). The product was purified by chromatography (ethyl acetate/petroleum ether = 1:6, v/v). Brown 12643

DOI: 10.1021/acs.joc.7b02423 J. Org. Chem. 2017, 82, 12640−12646

Article

The Journal of Organic Chemistry solid; yield: 71 mg, 80%; mp 102.2−104.6 °C; 1H NMR (400 MHz, acetone-d6): δ 9.35 (s, 1H), 8.19 (d, J = 8.4 Hz, 2H), 7.80 (d, J = 8.8 Hz, 2H), 7.47 (d, J = 8.4 Hz, 1H), 7.29−7.23 (m, 2H), 7.07 (t, J = 7.6 Hz, 1H), 6.48 (s, 1H), 3.89 (s, 3H), 2.30 (s, 3H), 1.99 (s, 3H); 13C NMR (100 MHz, acetone-d6): δ 150.76, 146.7, 136.2, 135.8, 133.2, 130.1, 128.9, 128.7, 127.1, 126.1, 124.4, 123.7, 121.0, 120.7, 110.9, 109.6, 29.7, 14.9, 14.6; IR (film): 3270, 3104, 3062, 2918, 2859, 2727, 1930, 1727, 1694, 1607 cm −1 ; HRMS (EI): M + calcd for C21H19N3O4S2 441.0817; found 441.0823. N-(3-(2,5-Dimethylthiophen-3-yl)-1-methyl-1H-indol-2-yl)methanesulfonamide (3n). The product was purified by chromatography (ethyl acetate/petroleum ether = 1:6, v/v). White solid; yield: 61 mg, 93%; mp 155.5−155.8 °C; 1H NMR (400 MHz, acetone-d6): δ 8.55 (s, 1H), 7.46 (d, J = 8.0 Hz, 1H), 7.42 (d, J = 8.0 Hz, 1H), 7.27 (dd, J = 7.6 Hz, 1H), 7.11 (dd, J1 = J2 = 7.4 Hz, 1H), 6.85 (s, 1H), 3.80 (s, 3H), 2.55 (s, 3H), 2.46 (s, 3H), 2.32 (s, 3H); 13C NMR (100 MHz, acetone-d6): δ 136.7, 135.8, 134.1, 130.9, 128.9, 126.4, 123.4, 120.73, 120.65, 110.9, 109.0, 40.8, 29.5, 15.2, 14.4; IR (film): 3255, 3056, 3015, 2919, 2858, 1723, 1694, 1617, 1566, 1470 cm−1; HRMS (EI): M+ calcd for C16H18N2O2S2 334.0810; found 334.0814. 4-Chloro-N-(1-methyl-3-(5-methylthiophen-2-yl)-1H-indol-2-yl)benzenesulfonamide (3o). The product was purified by chromatography (ethyl acetate/petroleum ether = 1:6, v/v). Light yellow solid; yield: 52 mg, 63%; mp 156.7−158.0 °C; 1H NMR (400 MHz, acetoned6): δ 9.32 (s, 1H), 7.72 (d, J = 8.0 Hz, 1H),7.53−7.43 (m, 3H), 7.33− 7.26 (m, 3H), 7.14 (dd, J1 = J2 = 7.4 Hz, 1H), 6.81−6.73 (m, 1H), 6.60−6.49 (m, 1H), 3.85 (s, 3H), 2.45 (s, 3H); 13C NMR (100 MHz, acetone-d6): δ 140.2, 139.5, 139.4, 135.8, 133.3, 129.6, 129.5, 127.7, 126.1, 125.9, 125.8, 124.0, 121.1, 120.5, 110.9, 108.1, 30.0, 15.1; IR (film): 3275, 3089, 3010, 2919, 2852, 1727, 1694, 1615, 1585 cm−1; HRMS (EI): M+ calcd for C20H17ClN2O2S2 416.0420; found 416.0424. 4-Chloro-N-(1-methyl-3-(3-methylthiophen-2-yl)-1H-indol-2-yl)benzenesulfonamide (3p). The product was purified by chromatography (ethyl acetate/petroleum ether = 1:6, v/v). White solid; yield: 64 mg, 77%; mp 241.4−242.2 °C; 1H NMR (400 MHz, acetone-d6): δ 9.20 (s, 1H), 7.53−7.49 (m, 3H), 7.36−7.26 (m, 4H), 7.22 (d, J = 5.2 Hz, 1H), 7.11 (dd, J1 = J2 = 7.6 Hz, 1H), 6.73 (d, J = 5.2 Hz, 1H), 3.88 (s, 3H), 1.84 (s, 3H); 13C NMR (100 MHz, acetone-d6): δ 139.9, 138.9, 135.8, 135.5, 130.6, 129.6, 128.9, 128.8, 128.7, 126.6, 124.9, 123.8, 121.0, 120.9, 111.0, 106.9, 29.9, 15.3; IR (film): 3510, 3266, 2929, 2847, 2583, 2245, 2016, 1915, 1689 cm−1; HRMS (EI): M+ calcd for C20H17ClN2O2S2 416.0420; found 416.0418. 4-Chloro-N-(3-(3,4-dimethylthiophen-2-yl)-1-methyl-1H-indol-2yl)benzenesulfonamide (3q). The product was purified by chromatography (ethyl acetate/petroleum ether = 1:6, v/v). White solid; yield: 62 mg, 72%; mp 106.6−109.0 °C; 1H NMR (400 MHz, acetoned6): δ 9.19 (s, 1H), 7.52−7.48 (m, 3H), 7.36−7.24 (m, 4H), 7.09 (dd, J1 = J2 = 7.4 Hz, 1H), 6.87 (s, 1H), 3.89 (s, 3H), 2.08 (s, 3H), 1.68 (s, 3H); 13C NMR (100 MHz, acetone-d6): δ 140.2, 138.7, 138.5, 135.8, 135.2, 129.3, 128.9, 128.7, 128.6, 126.8, 123.8, 120.94, 120.90, 120.4, 111.0, 107.7, 29.8, 15.3, 14.1; IR (film): 3363, 3265, 3067, 3013, 2938, 2852, 2228, 1691, 1613, 1585 cm−1; HRMS (EI): M+ calcd for C21H19ClN2O2S2 430.0576; found 430.0582. 4-Chloro-N-(1-methyl-3-(2-methylbenzo[b]thiophen-3-yl)1Hindol-2-yl)benzenesulfonamide (3r). The product was purified by chromatography (ethyl acetate/petroleum ether = 1:6, v/v). White solid; yield: 65 mg, 70%; mp 109.3−110.4 °C; 1H NMR (400 MHz, acetone-d6): δ 9.06 (s, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.53 (d, J = 8.4 Hz, 1H), 7.34−7.23 (m, 4H), 7.15−7.08 (m, 2H), 7.07−7.00 (m, 1H), 6.89 (dd, J = 8.4, 2.0 Hz, 2H), 3.93 (s, 3H), 2.30 (s, 3H); 13C NMR (100 MHz, acetone-d6): δ 140.9, 140.1, 138.9, 138.4, 138.0, 136.1, 129.0, 128.9, 128.2, 126.6, 126.0, 124.6, 124.5, 123.7, 123.5, 122.7, 121.0, 120.7, 111.0, 107.3, 29.7, 15.0; IR (film): 3254, 3109, 2944, 2908, 2852, 2249, 1903, 1723, 1694, 1617, 1585 cm−1; HRMS (EI): M+ calcd for C24H19ClN2O2S2 466.0576; found 466.0577. 4-Chloro-N-(1-methyl-3-(3-methylbenzo[b]thiophen-2-yl)-1Hindol-2-yl)enzenesulfonamide (3s). The product was purified by chromatography (ethyl acetate/petroleum ether = 1:6, v/v). White solid; yield: 49 mg, 53%; mp 185.2−186.7 °C; 1H NMR (400 MHz,

acetone-d6): δ 9.26 (s, 1H), 7.81 (d, J = 7.6 Hz, 1H), 7.62 (d, J = 7.2 Hz, 1H), 7.53 (d, J = 8.4 Hz, 1H), 7.45 (d, J = 8.8 Hz, 3H), 7.43−7.29 (m, 3H), 7.18−7.12 (m, 1H), 6.81 (d, J = 8.4 Hz, 2H), 3.92 (s, 3H), 2.04 (s, 3H); 13C NMR (100 MHz, acetone-d6): δ 141.4, 140.3, 139.9, 139.0, 135.9, 129.8, 129.6, 129.4, 129.0, 128.8, 126.4, 124.93, 124.86, 124.0, 122.51, 122.48, 121.3, 120.9, 111.2, 106.9, 29.8, 13.4; IR (film): 3254, 3060, 2941, 2843, 1723, 1694, 1615, 1585, 1518 cm−1; HRMS (EI): M+ calcd for C24H19ClN2O2S2 466.0576; found 466.0572. 4-Chloro-N-(3-(2,5-dimethyl-1H-pyrrol-3-yl)-1-methyl-1H-indol2-yl)benzenesulfonamide (3t). The product was purified by chromatography (dichloromethane/ethyl acetate/petroleum ether = 3:1:6, v/v). Red solid; yield: 50 mg, 60%; m.p.178.8−179.1 °C; 1H NMR (400 MHz, DMSO): δ 11.01 (s, 1H), 10.72 (s, 1H), 8.23 (d, J = 8.0 Hz, 1H), 7.75 (d, J = 8.4 Hz, 2H), 7.57−7.45 (m, 3H), 7.32−7.24 (m, 1H), 7.20−7.12 (m, 1H), 5.21 (s, 1H), 3.79 (s, 3H), 2.37 (s, 3H), 2.16 (s, 3H); 13C NMR (100 MHz, DMSO): δ 140.1, 140.0, 138.3, 135.0, 129.9, 129.48, 129.46, 127.6, 124.0, 122.6, 122.3, 118.0, 110.7, 95.2, 30.0, 13.4, 10.8; IR (film): 3324, 3107, 3086, 2925, 2876, 2546, 2114, 1713, 1667 cm −1 ; HRMS (ESI): [M−H] − calcd for C21H19ClN3O2S− 412.0892; found 412.0923. 4-Chloro-N-(1,1′,2′-trimethyl-1H,1′H-[3,3′-biindol]-2-yl)benzenesulfonamide (3u). The product was purified by chromatography (dichloromethane/ethyl acetate/petroleum ether = 3:1:6, v/v). Red solid; yield: 49 mg, 53%; mp 241.2−242.2 °C; 1H NMR (400 MHz, DMSO): δ 10.99 (s, 1H), 8.36 (d, J = 8.0 Hz, 1H), 7.69 (d, J = 8.0 Hz, 1H), 7.63 (d, J = 8.8 Hz, 2H), 7.55 (d, J = 8.0 Hz, 1H), 7.44 (d, J = 8.0 Hz, 1H), 7.35−7.29 (m, 1H), 7.26−7.13 (m, 4H), 7.01 (dd, J1 = J2 = 7.2 Hz, 1H), 3.80 (s, 3H), 3.75 (s, 3H), 2.74 (s, 3H); 13C NMR (100 MHz, DMSO): δ 142.1, 139.1, 138.3, 136.7, 134.9, 132.1, 131.4, 129.54, 129.47, 129.32, 124.0, 122.9, 122.8, 122.7, 122.4, 121.8, 118.5, 117.7, 110.8, 109.5, 40.5, 30.2, 10.4; IR (film): 3583, 2962, 2923, 2848, 2457, 2117, 1768, 1689 cm−1; HRMS (ESI): [M + Na]+ calcd for C25H22ClN3O2SNa 486.1013; found 486.1018. General Procedure for the Synthesis of 5. A 25 mL roundbottom flask was charged with 1 (0.2 mmol), 4 (1.0 mmol), TfOH (50 mol %), and DCE (2 mL). The reaction mixture was stirred at 35 °C (oil bath) for 1 h. After cooling to room temperature, the resulted mixture was evaporated under reduced pressure and the residue was purified by flash column chromatography on a silica gel to give pure product 5. N-(1-Benzyl-3-(p-tolyl)-1H-indol-2-yl)-4-methylbenzenesulfonamide (5a). The product was purified by chromatography (ethyl acetate/petroleum ether = 1:8, v/v). White solid; yield: 68 mg, 73%; m.p.182.3−182.6 °C; 1H NMR (400 MHz, DMSO): δ 10.52 (s, 1H), 7.46 (d, J = 8.0 Hz, 1H), 7.36 (d, J = 8.0 Hz, 1H), 7.33−7.30 (m, 2H), 7.25 (d, J = 7.2 Hz, 1H), 7.21−7.14 (m, 4H), 7.10 (d, J = 8.0 Hz, 2H), 7.06−6.98 (m, 2H), 6.94 (d, J = 8.0 Hz, 2H), 6.88 (d, J = 8.4 Hz, 2H), 5.55 (s, 2H), 2.30 (s, 3H), 2.25 (s, 3H); 13C NMR (100 MHz, DMSO): δ 143.1, 138.5, 137.4, 135.4, 134.4, 130.2, 129.5, 129.3, 128.99, 127.7, 127.3, 127.2, 126.8, 126.3, 125.4, 123.1, 120.5, 119.7, 113.7, 111.3, 45.9, 21.5, 21.3; IR (film): 3586, 3253, 2961, 2924, 2854, 2351, 1664, 1599, 1565 cm−1; HRMS (EI): M+ calcd for C29H26N2O2S 466.1715; found 466.1719. N-(1-Benzyl-3-(2,5-dimethylphenyl)-1H-indol-2-yl)-4-methylbenzenesulfonamide (5b). The product was purified by chromatography (ethyl acetate/petroleum ether = 1:8, v/v). White solid; yield: 35 mg, 36%; mp 145.5−146.4 °C; 1H NMR (400 MHz, acetone-d6): δ 9.13 (s, 1H), 7.39−7.21 (m, 6H), 7.19−7.09 (m, 4H), 6.99 (m, 5H), 6.89 (d, J = 7.6 Hz, 1H), 5.78 (d, J = 16.4 Hz, 1H), 5.59 (d, J = 16.4 Hz, 1H), 2.35 (s, 3H), 2.24 (s, 3H), 1.82 (s, 3H); 13C NMR (100 MHz, acetone-d6): δ 143.5, 139.4, 138.4, 135.3, 135.2, 134.7, 132.8, 132.6, 130.7, 129.9, 129.3, 128.4, 128.1, 127.9, 127.5, 127.2, 126.9, 123.4, 121.1, 120.6, 115.0, 111.6, 46.8, 21.5, 20.9, 20.4; IR (film): 3246, 3030, 2920, 2856, 2346, 1727, 1691, 1598, 1496, 1462 cm−1; HRMS (EI): M+ calcd for C30H28N2O2S 480.1871; found 480.1867. N-(1-Benzyl-3-(2,4-dimethylphenyl)-1H-indol-2-yl)-4-methylbenzenesulfonamide (5c). The product was purified by chromatography (ethyl acetate/petroleum ether = 1:8, v/v). White solid; yield: 91 mg, 95%; mp 168.3−170.0 °C; 1H NMR (400 MHz, acetone-d6): δ 9.09 (s, 1H), 7.37−7.20 (m, 6H), 7.16 (m, 4H), 7.01 (m, 4H), 6.87 (d, J = 12644

DOI: 10.1021/acs.joc.7b02423 J. Org. Chem. 2017, 82, 12640−12646

Article

The Journal of Organic Chemistry 7.6 Hz, 1H), 6.82 (s, 1H), 5.78 (d, J = 16.4 Hz, 1H), 5.58 (d, J = 16.4 Hz, 1H), 2.37 (s, 3H), 2.34 (s, 3H), 1.84 (s, 3H); 13C NMR (100 MHz, acetone-d6): δ 143.6, 139.3, 138.4, 137.6, 137.1, 135.2, 131.7, 131.4, 130.1, 129.7, 129.3, 128.0, 127.9, 127.5, 127.2, 126.9, 126.7, 123.4, 121.1, 120.6, 114.9, 111.6, 46.8, 21.5, 21.2, 20.8; IR (film): 3251, 3031, 2920, 2856, 2727, 2254, 1911, 1727, 1694, 1598 cm−1; HRMS (EI): M+ calcd for C30H28N2O2S 480.1871; found 480.1869. N-(1-Benzyl-3-(3,4-dimethylphenyl)-1H-indol-2-yl)-4-methylbenzenesulfonamide (5d). The product was purified by chromatography (ethyl acetate/petroleum ether = 1:8, v/v). White solid; yield: 43 mg, 45%; m.p.185.4−185.6 °C; 1H NMR (400 MHz, acetone-d6): δ 9.23 (s, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.33−7.23 (m, 5H), 7.21−7.15 (m, 3H), 7.10 (s, 1H), 7.08−7.03 (m, 1H), 7.02− 6.87 (m, 4H), 5.70 (s, 2H), 2.30 (s, 3H), 2.26 (s, 3H), 2.18 (s, 3H); 13 C NMR (100 MHz, acetone-d6): δ 143.7, 139.3, 138.2, 136.8, 135.5, 134.7, 131.5, 130.9, 130.1, 129.5, 129.3, 127.9, 127.7, 127.6, 127.5, 127.3, 126.5, 123.7, 120.9, 120.5, 115.0, 111.5, 46.8, 21.5, 19.7, 19.5; IR (film): 3271, 3016, 2955, 2924, 2879, 2851, 2349, 1738, 1463 cm−1; HRMS (MALDI-TOF): [M + H]+ calcd for C30H29N2O2S 481.1944; found: 481.1940. N-(1-Benzyl-3-mesityl-1H-indol-2-yl)-4-methylbenzenesulfonamide (5e). The product was purified by chromatography (ethyl acetate/petroleum ether = 1:8, v/v). White solid; yield = 94%; mp 181.6−182.0 °C; 1H NMR (400 MHz, acetone-d6): δ 8.76 (s, 1H), 7.35 (d, J = 8.4 Hz, 2H), 7.32−7.21 (m, 4H), 7.16−7.09 (m, 3H), 7.08−6.97 (m, 4H), 6.72 (s, 2H), 5.57 (s, 2H), 2.84 (s, 3H), 2.38 (s, 3H), 2.30 (s, 3H), 1.90 (s, 3H); 13C NMR (100 MHz, acetone-d6): δ 143.5, 139.7, 139.3, 138.6, 137.2, 135.6, 129.8, 129.7, 129.4, 128.6, 128.2, 127.9, 127.2, 126.9, 126.90, 126.88, 123.4, 120.7, 120.6, 113.6, 111.6, 46.5, 21.5, 21.3, 20.8; IR (film): 3583, 3230, 3060, 3030, 2956, 2923, 2852, 2349, 1736, 1659 cm−1; HRMS (EI): M+ calcd for C31H30N2O2S 494.2028; found 494.2032. N-(1-Benzyl-3-(4-methoxyphenyl)-1H-indol-2-yl)-4-methylbenzenesulfonamide (5f). The product was purified by chromatography (ethyl acetate/petroleum ether = 1:8, v/v). White solid; yield: 86 mg, 89%; mp 168.3−170.0 °C; 1H NMR (400 MHz, acetone-d6): δ 9.21 (s, 1H), 7.55 (d, J = 8.0 Hz, 1H), 7.38 (d, J = 8.4 Hz, 1H), 7.32−7.25 (m, 4H), 7.25−7.15 (m, 6H), 7.10−7.02 (m, 1H), 6.93 (d, J = 8.0 Hz, 2H), 6.74 (d, J = 8.8 Hz, 2H), 5.69 (s, 2H), 3.83 (s, 3H), 2.31 (s, 3H); 13 C NMR (100 MHz, acetone-d6): δ 159.1, 143.9, 139.3, 138.0, 135.4, 130.8, 129.8, 129.3, 127.9, 127.7, 127.5, 127.4, 126.5, 126.3, 123.7, 120.8, 120.4, 114.7, 114.4, 111.5, 55.4, 46.8, 21.4; IR (film): 3254, 3062, 3013, 2934, 2835, 2254, 1888, 1725, 1693, 1611 cm−1; HRMS (ESI): [M + Na]+ calcd for C29H26N2O3SNa 505.1556; found 505.1554. N-(1-Benzyl-3-(2,5-dimethoxyphenyl)-1H-indol-2-yl)-4-methylbenzenesulfonamide (5g). The product was purified by chromatography (ethyl acetate/petroleum ether = 1:8, v/v). White solid; yield: 100 mg, 98%; m.p.183.0−183.1 °C; 1H NMR (400 MHz, acetone-d6): δ 8.04 (s, 1H), 7.49 (d, J = 8.0 Hz, 1H), 7.37 (d, J = 8.4 Hz, 1H), 7.32−7.28 (m, 2H), 7.24 (d, J = 7.2 Hz, 1H), 7.22−7.11 (m, 5H), 7.05 (dd, J1 = J2 = 7.4 Hz, 1H), 6.97−6.87 (m, 3H), 6.79 (dd, J = 9.2, 3.2 Hz, 1H), 6.45 (d, J = 2.8 Hz, 1H), 5.89 (s, 1H), 5.63 (s, 1H), 3.77 (s, 6H), 2.29 (s, 3H); 13C NMR (100 MHz, acetone-d6): δ 155.0, 150.3, 144.5, 139.2, 136.1, 135.9, 129.9, 129.7, 129.3, 127.9, 127.7, 127.5, 126.6, 123.6, 123.4, 121.1, 120.2, 116.9, 114.8, 113.3, 111.8, 109.0, 57.8, 55.6, 47.1, 21.3; IR (film): 3851, 3227, 3061, 2954, 2926, 2853, 2352, 1652, 1605, 1567 cm−1; HRMS (MALDI-TOF): [M + H]+ calcd for C30H29N2O4S 513.1843; found 513.1840. N-(1-Benzyl-3-(naphthalen-2-yl)-1H-indol-2-yl)-4-methylbenzenesulfonamide (5h). The product was purified by chromatography (ethyl acetate/petroleum ether = 1:8, v/v). White solid; yield: 72 mg, 72%; mp 119.3−119.7 °C; 1H NMR (400 MHz, DMSO): δ 10.60 (s, 1H), 7.83 (d, J = 8.4 Hz, 1H), 7.76 (d, J = 7.6 Hz, 1H), 7.48−7.32 (m, 6H), 7.32−7.20 (m, 5H), 7.14 (dd, J1 = J2 = 7.6 Hz, 1H), 7.99−7.89 (m, 3H), 6.85 (d, J = 8.0 Hz, 1H), 6.36 (d, J = 8.0 Hz, 2H), 5.74 (d, J = 16.4 Hz, 1H), 5.57 (d, J = 16.4 Hz, 1H), 1.92 (s, 3H); 13C NMR (100 MHz, DMSO): δ 141.5, 138.0, 136.5, 133.6, 133.2, 131.5, 130.1, 128.5, 128.3, 128.13, 128.26, 127.9, 127.2, 127.0, 126.8, 126.2, 126.0, 125.5, 125.25, 125.19, 125.0, 122.5, 119.9, 119.8, 111.8, 110.9, 45.6,

20.8; IR (film): 3586, 3242, 2954, 2924, 2872, 2853, 2725, 2346, 1736, 1606 cm−1; HRMS (EI): M+ calcd for C32H26N2O2S 502.1715; found 502.1709.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b02423. 1 H NMR and 13C NMR spectra for all new compounds (PDF) X-ray crystallographic data of compound 3o (CIF)

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected] *E-mail: [email protected] ORCID

Ping Lu: 0000-0002-3221-3647 Yanguang Wang: 0000-0002-5096-7450 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank the National Natural Science Foundation of China (Nos. 21472173; 21632003) for financial support. REFERENCES

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DOI: 10.1021/acs.joc.7b02423 J. Org. Chem. 2017, 82, 12640−12646