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Br2- or HBr-catalyzed synthesis of asymmetric 3,3-di(indolyl)indolin-2-ones

  • Yanni Li , Deqiang Liang EMAIL logo , Xiangguang Li , Wenzhong Huang , Lin Yuan , Baoling Wang and Ping Cheng
Published/Copyright: January 28, 2017
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Heterocyclic Communications
From the journal Heterocyclic Communications Volume 23 Issue 1

Abstract

Under the catalysis of 1 mol% of Br2 or HBr at room temperature, indoles undergo a rapid reaction with 3-hydroxy-3-(indol-3-yl)indolin-2-ones to give asymmetric 3,3-di(indol-3-yl)indolin-2-ones with high efficiency and wide substrate scope. This is a rare example of Br2 acting as a Lewis acid catalyst. Theoretical calculations suggest that both the catalytic activity of the catalysts and the stability of reaction intermediates are responsible for the high efficiency of this reaction.

Keywords: alcohols; alkylation; C–C coupling; halogens; homogeneous catalysis

Introduction

The indole system is a ubiquitous feature of alkaloids and represents a privileged structural motif for pharmaceutically active compounds [1], [2], [3], [4], [5], [6]. In this context, 3,3-di(indolyl)indolin-2-ones, frequently referred to as trisindolines, are a class of natural products isolated from marine-derived bacteria [7], [8], [9] and terrestrial plants [10]. They exhibit activities as anticancer [11], [12], [13], antimicrobial, anticonvulsant [14] and spermicidal agents [15].

Despite the plethora of preparations of symmetric trisindolines from indoles and isatins [16], reports on the synthesis of asymmetric 3,3-di(indolyl)indolin-2-ones are rare. In 2006, Ji and co-workers disclosed a facile synthesis of such compounds from 3-hydroxy-3-(indolyl)indolin-2-ones and indoles catalyzed by ceric ammonium nitrate (CAN). The reaction was run under ultrasound irradiation with a rather high catalyst content of 10 mol% [17]. More recently, an elegant synthesis of asymmetric 3,3-di(indolyl)indolin-2-ones in the ionic liquid N,N,N,N-tetramethylguanidinium trifluoroacetate (TMGT) as the solvent was realized by Rad-Moghadam and co-workers. This reaction featured a narrow substrate scope [18]. Mamaghani and co-workers reported the successful preparation of the title compounds from indoles and isatins by using montmorillonite KSF clay as a recyclable heterogeneous catalyst, however, both a high temperature and a high catalyst load were required [19]. There were two additional attempts in which no substrate scope was explored. Thus, one asymmetric 3,3-di(indolyl)indolin-2-one was afforded in a 40% yield under the catalysis of 5 mol% of toxic Hg(ClO4)2·3H2O [20]. The Lewis acids Sn(OTf)2 and Cu(OTf)2 were also reported to catalyze the reaction but at a high load of 10 mol% and a long reaction time was required [21]. Given our ongoing interest in the bromine effect [16], [22], [23], [24], [25], [26], we examined the catalytic activity of Br2 in this dehydrative C–C coupling reaction and found that bromine is an excellent catalyst. It should be noted that in a sharp contrast to the wide application of molecular iodine in organic synthesis, elemental bromine is underrated and has rarely been used as a Lewis acid catalyst, which is partly due to its high vapor pressure and corrosiveness [27], [28]. The use of hydrobromic acid as catalyst was also explored in this work.

Results and discussion

The dehydrative coupling of 3-hydroxy-3-(indol-3-yl)indolin-2-one (1a) and 1-methylindole (2a) was investigated as the model reaction. We were pleased to find that in the presence of only 1 mol% of Br2 in MeCN at room temperature, this reaction was completed rapidly within 6 min and asymmetric 3,3-di(indol-3-yl)indolin-2-one 3a was obtained in a nearly quantitative yield. An excellent yield was still achieved after 50 min in the presence of a reduced catalyst loading of 0.5 mol%. The remarkable role of Br2 could not be replaced by the use of N-bromosuccinimide (NBS), a well-known alternative to Br2. The trisindoline 3a was obtained in 96% yield within 10 min in a HBr-catalyzed reaction using 48% hydrobromic acid [29], [30]. With CuBr2 [31], [32], [33] as the catalyst, the product 3a was obtained in 93% yield after a much longer reaction time of 6 h. Notably, the reaction catalyzed by Br2 was hardly affected by the addition of water, whereas aqueous HBr was less active when 4Å molecular sieves were added, probably due to adsorption of the catalyst. In the presence of I2 as catalyst, trisindoline 3a was obtained in 94% yield within 20 min. The reaction was also catalyzed by a 47% aqueous HI but it took 6 h for the reaction to be completed. Product 3a was obtained after prolonged reaction times in the presence of H2SO4, TsOH, BF3·Et2O, AlCl3 or SnCl4 as the catalyst. Next, the solvents were screened. No reaction occurred in CH2Cl2 under the catalysis of 1 mol% of Br2 and only trace amounts of 3a was observed in toluene after 12 h under otherwise similar conditions. Reactions performed in tetrahydrofuran and ethanol were completed in 6 h and 12 h, respectively. Product 3a was obtained in low yield in N,N-dimethylformamide after 12 h.

Under optimal conditions the reaction was conducted in MeCN at ambient temperature in the presence of 1 mol% of Br2 as the catalyst. Aqueous HBr is also a good catalyst. Both catalysts were used to evaluate the substrate scope with respect to both coupling partners (Scheme 1). In general, the HBr-catalyzed reactions proceed slower and with slightly lower yields than the reactions catalyzed by Br2. As can be seen from Scheme 1, many substituents in substrates 1 and 2 are tolerated and products 3 are obtained in high yields after short reaction times. The only exceptions are the reactions of substrate 1f which are conducted in the presence of 5 mol% of the catalyst, proceed efficiently at 50°C and require much longer reaction times.

Scheme 1 Substrate scope.
Scheme 1

Substrate scope.

In an effort to gain insights into the extraordinary performances of Br2 and HBr, theoretical calculations of natural population atomic (NPA) charges on C(3) of 3-hydroxy-3-(indol-3-yl)indolin-2-one (1a) upon activation by a series of Brønsted and Lewis acids were carried out (Figure 1). Upon coordination of the hydroxyl oxygen atom to acid, the positivity of α-carbon is enhanced. The results at the M062X/def2TZVP level [34], [35] demonstrate that while all acids function in molecular forms, in terms of acidity, Br2, HBr or I2 are not superior to other selected acids, including HI, H2SO4, TFA, BF3 and AlCl3. In addition, the positivity of the α-carbon is enhanced only slightly when the solvent effect of MeCN is considered (M062X/def2TZVP+MeCN) [36]. It can be suggested that acidity is not be the primary cause of the robust catalytic activities of Br2 and HBr in this reaction; the origin of which remains unclear at this stage. Further exploration still needs to be carried out and is ongoing in our laboratory.

Figure 1 NPA charge calculations for C(3) of 1a at the M062X/def2TZVP and SMD-MeCN-M062X/def2TZVP levels of theory.
Figure 1

NPA charge calculations for C(3) of 1a at the M062X/def2TZVP and SMD-MeCN-M062X/def2TZVP levels of theory.

Next, the stabilities of diphenylmethylium cation, triphenylmethylium cation and 3-(indol-3-yl)-2-oxoindolin-3-ylium cation I were analyzed (Figure 2). DFT calculations at the M062X/def2TZVP level revealed that intermediate cation I is more stable than the triphenylmethylium cation, and that the solvent greatly stabilizes all these cations (M062X/def2TZVP+MeCN). Thus, it can be suggested that both the catalytic activity of the catalysts and the stability of reaction intermediates are responsible for the extremely high efficiency of this reaction.

Figure 2 Stabilities of diphenylmethylium, triphenylmethylium and 3-(indol-3-yl)-2-oxoindolin-3-ylium I at the M062X/def2TZVP level.
Figure 2

Stabilities of diphenylmethylium, triphenylmethylium and 3-(indol-3-yl)-2-oxoindolin-3-ylium I at the M062X/def2TZVP level.

Conclusions

A novel Br2- or HBr-catalyzed dehydrative coupling of indoles with 3-hydroxy-3-(indol-3-yl)indolin-2-ones was developed. This reaction provides direct access to biologically important asymmetric 3,3-di(indolyl)indolin-2-ones at low cost and high efficiency, with good functional group tolerance. Bromine is a novel Lewis acid in this study, examples of which are scarce [16], [22], [23], [24], [25], [26]. The results of DFT calculations suggest that both the catalytic activity of the catalyst and the stability of the reaction intermediate are responsible for the high efficiency of this reaction.

Experimental

Thin-layer chromatography (TLC) was carried out using silica gel GF254 plates. 1H NMR (400 MHz) and 13C NMR (100 MHz) spectra were recorded in DMSO-d6 at 25°C on a Bruker Ascend 400 spectrometer (Bruker, Karlsruhe, Baden-Württemberg, Germany) using TMS as internal standard. High-resolution mass spectra (HR-MS) were obtained on a Bruker micro TOF II Focus spectrometer (Bruker Daltronics, Bremen, Germany) using electrospray ionization (ESI).

Optimization of all molecular geometries and vibrational analyses were calculated at M06-2X functions with the def2-TZVP basis set by using Gaussian 09 program (Gaussian, Wallingford, Connecticut, USA) [37]. A natural bonding orbital (NBO) analysis for structures was also performed to determine NPA charges by using the NBO 3.1 package implemented in Gaussian 09. All calculated structures were true minima (no imaginary frequencies). Solvent effect at the M062X/def2TZVP level was calculated using the solvent model density (SMD) approach [36]. The Gibbs free energy change (ΔG) of reactions of ‘ROH+H+=R++H2O’ was used to compare the stabilities of different cations [38], [39], [40], [41], [42].

General procedure with Br2 as the catalyst (method A)

To a stirred solution of 3-hydroxy-3-(indol-3-yl)indolin-2-one 1 (0.5 mmol) and indole 2 (0.55 mmol) in MeCN (2.5 mL) was added a solution of Br2 (0.026 mL, 0.5 mmol) in MeCN (0.5 mL), and the mixture was stirred at ambient temperature. After substrate 1 was consumed, as indicated by TLC, the reaction mixture was quenched with saturated aqueous solution of Na2S2O3 (0.5 mL) and water (20 mL), and stirred for an additional 10 min. The precipitated solid was filtered, washed with water (20 mL) and then with CH2Cl2 (10 mL), and dried under reduced pressure to afford asymmetric 3,3-di(indol-3-yl)indolin-2-one 3.

General procedure with HBr as the catalyst (method B)

To a stirred solution of 3-hydroxy-3-(indol-3-yl)indolin-2-one 1 (0.5 mmol) and indole 2 (0.55 mmol) in MeCN (2.5 mL) was added a solution of HBr (0.073 mL, 0.5 mmol) in MeCN (0.5 mL), and the mixture was stirred at ambient temperature. After substrate 1 was consumed, as indicated by TLC, the reaction mixture was quenched with saturated aqueous solution of NaHCO3 (0.5 mL) and water (20.0 mL), and stirred for an additional 10 min. The precipitated solid was filtered, washed with water (20 mL) and then with CH2Cl2 (10 mL), and dried under reduced pressure to afford asymmetric 3,3-di(indol-3-yl)indolin-2-one 3.

1-Methyl-1H,1″H-[3,3′:3′,3″-terindol]-2′(1′H)-one (3a)

This compound was obtained from 1a and 2a; yield 97%, 6 min, method A; yield 96%, 10 min, method B; off-white solid; mp 310–311°C (dec.); 1H NMR: δ 3.71 (s, 3H), 6.77–6.86 (m, 4H), 6.92 (dd, J=7.4, 7.2 Hz, 1H), 6.97–7.03 (m, 2H), 7.08 (dd, J=7.0, 7.0 Hz, 1H), 7.19–7.25 (m, 4H), 7.36 (dd, J=8.2, 9.8 Hz, 2H), 10.60 (s, 1H), 10.96 (s, 1H); 13C NMR δ 179.1, 141.8, 137.8, 137.4, 135.0, 128.9, 128.3, 126.6, 126.1, 125.4, 124.8, 122.0, 121.6, 121.5, 121.4, 121.1, 118.8, 118.7, 114.7, 114.0, 112.1, 110.2, 110.1, 53.0, 32.8. HR-MS. Calcd for C25H20N3O+ ([M+H]+): m/z 378.1601. Found: m/z 378.1602.

1H,1″H-[3,3′:3′,3″-terindol]-2′(1′H)-one (3b)

This compound was obtained from 1a and 2b; yield 92%, 60 min, method A; yield 92%, 180 min, method B; off-white solid; mp 319–320°C (dec.); 1H NMR: δ 6.78–7.03 (m, 8H), 7.23 (d, J=4.8 Hz, 4H), 7.35 (d, J=6.7 Hz, 2H), 10.60 (s, 1H), 10.95 (s, 2H); 13C NMR: δ 179.2, 141.8, 137.4, 135.1, 128.3, 126.2, 125.4, 124.8, 121.9, 121.4, 121.3, 118.7, 114.8, 112.1, 110.0, 53.1. HR-MS. Calcd for C24H18N3O+ ([M+H]+): m/z 364.1444. Found: m/z 364.1447.

5-Methoxy-1H,1″H-[3,3′:3′,3″-terindol]-2′(1′H)-one (3c)

This compound was obtained from 1a and 2c; yield 95%, 5 min, method A; yield 92%, 15 min, method B; off-white solid; mp 307–308°C (dec.); 1H NMR: δ 3.52 (s, 3H), 6.67–6.71 (m, 2H), 6.79–6.83 (m, 2H), 6.89 (d, J=2.5 Hz, 1H), 6.94 (ddd, J=0.8, 7.6, 7.5 Hz, 1H), 6.99–7.04 (m, 2H), 7.22–7.27 (m, 4H), 7.37 (d, J=8.1 Hz, 1H), 10.61 (s, 1H), 10.83 (d, J=1.9 Hz, 1H), 10.98 (d, J=1.7 Hz, 1H); 13C NMR: δ 179.2, 152.9, 141.9, 137.4, 135.1, 132.6, 128.3, 126.6, 126.2, 125.6, 125.4, 124.9, 121.9, 121.4, 121.2, 118.7, 114.6, 114.3, 112.5, 112.1, 110.9, 110.0, 103.8, 55.6, 53.1. HR-MS. Calcd for C25H20N3O2+ ([M+H]+) m/z 394.1550. Found m/z 394.1546.

5-Bromo-1H,1″H-[3,3′:3′,3″-terindol]-2′(1′H)-one (3d)

This compound was obtained from 1a and 2d; yield 86%, 10 min, method A; yield 87%, 30 min, method B; white solid; mp 302–303°C (dec.); 1H NMR: δ 6.79–7.04 (m, 6H), 7.13-7.27 (m, 4H), 7.35 (dd, J=6.1, 6.1 Hz, 2H), 7.44 (s, 1H), 10.65 (s, 1H), 10.97 (s, 1H), 11.20 (s, 1H); 13C NMR: δ 179.1, 141.8, 137.4, 136.2, 134.6, 128.5, 128.0, 126.3, 126.0, 125.4, 124.8, 124.0, 123.7, 122.1, 121.5, 120.7, 118.9, 114.6, 114.5, 114.2, 112.2, 111.4, 110.2, 52.8. HR-MS. Calcd for C24H17BrN3O+ ([M+H]+): m/z 442.0550. Found: m/z 442.0551.

6-Chloro-1H,1″H-[3,3′:3′,3″-terindol]-2′(1′H)-one (3e)

This compound was obtained from 1a and 2e; yield 93%, 10 min, method A; yield 90%, 30 min, method B; white solid; mp 281–282°C (dec.); 1H NMR: δ 6.77–7.02 (m, 7H), 7.15–7.25 (m, 4H), 7.35 (d, J=7.8 Hz, 1H), 7.41 (s, 1H), 10.63 (s, 1H), 10.98 (s, 1H), 11.14 (s, 1H); 13C NMR: δ 179.0, 141.8, 137.8, 137.4, 134.8, 128.4, 126.2, 126.1, 125.8, 125.3, 125.0, 124.7, 122.8, 122.0, 121.4, 120.9, 119.0, 118.8, 115.1, 114.6, 112.1, 111.7, 110.2, 52.9. HR-MS. Calcd for C24H17ClN3O+ ([M+H]+): m/z 398.1055. Found: m/z 398.1056.

7-Methyl-1H,1″H-[3,3′:3′,3″-terindol]-2′(1′H)-one (3f)

This compound was obtained from 1a and 2f; yield 95%, 2 min, method A; yield 93%, 10 min, method B; yellow solid; mp 220–221°C; 1H NMR: δ 2.45 (s, 3H), 6.73 (dd, J=7.1, 7.3 Hz, 1H), 6.80–6.87 (m, 4H), 6.94 (dd, J=6.8, 7.0 Hz, 1H), 7.00–7.06 (m, 3H), 7.22–7.31 (m, 3H), 7.37 (d, J=7.8 Hz, 1H), 10.62 (s, 1H), 10.95 (s, 1H), 10.98 (s, 1H); 13C NMR: δ 179.3, 141.8, 137.4, 136.9, 135.2, 128.3, 126.2, 125.9, 125.4, 124.7, 124.5, 121.9, 121.5, 121.4, 121.0, 119.0, 118.8, 118.7, 115.3, 114.8, 112.1, 110.0, 53.1, 17.2. HR-MS. Calcd for C25H20N3O+ ([M+H]+): m/z 378.1601. Found: m/z 378.1606.

2,2″-Dimethyl-1H,1″H-[3,3′:3′,3″-terindol]-2′(1′H)-one (3g)

This compound was obtained from 1b and 2g; yield 90%, 60 min, method A; yield 90%, 120 min, method B; pinkish solid; mp 290–291°C; 1H NMR: δ 1.93 (s, 3H), 2.07 (s, 3H), 6.45 (d, J=7.3 Hz, 1H), 6.58–6.70 (m, 3H), 6.84–6.95 (m, 4H), 7.13–7.23 (m, 4H), 10.51 (s, 1H), 10.83 (s, 1H), 10.86 (s, 1H); 13C NMR: δ 179.8, 141.7, 136.1, 135.5, 135.4, 134.4, 132.5, 128.3, 128.2, 127.5, 125.9, 121.7, 120.2, 120.0, 119.8, 119.8, 118.4, 118.4, 110.9, 110.8, 109.9, 52.9, 13.6, 13.4. HR-MS. Calcd for C26H22N3O+ ([M+H]+): m/z 392.1757. Found: m/z 392.1749.

5″-Methoxy-1-methyl-1H,1″H-[3,3′:3′,3″-terindol]-2′(1′H)-one (3h)

This compound was obtained from 1c and 2a; yield 91%, 10 min, method A; yield 90%, 30 min, method B; off-white solid; mp 303–304°C; 1H NMR: δ 3.52 (s, 3H), 3.72 (s, 3H), 6.65–6.71 (m, 2H), 6.84–7.01 (m, 5H), 7.10 (dd, J=7.1, 6.6 Hz, 1H), 7.22–7.28 (m, 4H), 7.39 (d, J=7.7 Hz, 1H), 10.63 (s, 1H), 10.83 (s, 1H); 13C NMR: δ 179.1, 152.9, 141.8, 137.8, 135.0, 132.6, 129.0, 128.4, 126.6, 126.5, 125.6, 125.4, 122.0, 121.5, 118.8, 114.1, 113.9, 112.6, 110.9, 110.2, 110.0, 103.6, 55.6, 52.9, 32.8. HR-MS. Calcd for C26H22N3O2+ ([M+H]+): m/z 408.1707. Found: m/z 408.1710.

6″-Chloro-1-methyl-1H,1″H-[3,3′:3′,3″-terindol]-2′(1′H)-one (3i)

This compound was obtained from 1d and 2a; yield 93%, 20 min, method A; yield 93%, 30 min, method B; off-white solid; mp 283–284°C; 1H NMR: δ 3.71 (s, 3H), 6.82–6.86 (m, 2H), 6.88 (s, 1H), 6.91 (d, J=2.4 Hz, 1H), 6.92–7.00 (m, 2H), 7.09 (ddd, J=0.8, 7.2, 7.2 Hz, 1H), 7.18 (d, J=8.0 Hz, 1H), 7.22–7.26 (m, 3H), 7.38 (d, J=8.3 Hz, 1H), 7.41 (d, J=1.8 Hz, 1H), 10.65 (s, 1H), 11.12 (d, J=1.6 Hz, 1H); 13C NMR: δ 178.9, 141.7, 137.8, 137.7, 134.7, 128.9, 128.5, 126.4, 126.3, 125.8, 125.3, 125.0, 122.7, 122.1, 121.6, 121.2, 119.1, 118.9, 115.0, 113.9, 111.7, 110.3, 110.2, 100.0, 52.8, 32.8. HR-MS. Calcd for C25H19ClN3O+ ([M+H]+): m/z 412.1211. Found: m/z 412.1213.

1,7″-Dimethyl-1H,1″H-[3,3′:3′,3″-terindol]-2′(1′H)-one (3j)

This compound was obtained from 1e and 2a; yield 95%, 2 min, method A; yield 93%, 10 min, method B; off-white solid; mp 311–312°C (dec.); 1H NMR: δ 2.44 (s, 3H), 3.71 (s, 3H), 6.72 (dd, J=7.1, 7.3 Hz, 1H), 6.81–6.86 (m, 4H), 6.93 (dd, J=7.0, 7.0 Hz, 1H), 7.01 (dd, J=7.7, 12.8 Hz, 2H), 7.09 (dd, J=7.3, 6.7 Hz, 1H), 7.21–7.30 (m, 3H), 7.38 (d, J=8.0 Hz, 1H), 10.61 (bs, 1H), 10.95 (s, 1H); 13C NMR: δ 179.1, 141.8, 137.8, 136.8, 135.1, 128.9, 128.3, 126.6, 125.8, 125.4, 124.5, 121.9, 121.8, 121.5, 121.1, 119.0, 118.8, 118.6, 115.2, 114.0, 110.2, 110.0, 53.0, 32.8, 17.2. HR-MS. Calcd for C26H22N3O+ ([M+H]+): m/z 392.1757. Found: m/z 392.1759.

4′-Chloro-1-methyl-1H,1″H-[3,3′:3′,3″-terindol]-2′(1′H)-one (3k)

This compound was obtained from 1f and 2a; yield 88%, 12 h, method A but using 5 mol% of catalyst at 50°C; yield 83%, 24 h, method B but using 5 mol% of catalyst at 50°C; off-white solid; mp 270–271°C (dec.); 1H NMR: δ 3.73 (s, 3H), 6.84–6.97 (m, 5H), 7.01 (d, J=7.5 Hz, 1H), 7.06 (dd, J=7.3, 7.3 Hz, 1H), 7.13 (dd, J=7.4, 7.3 Hz, 1H), 7.21 (d, J=8.0 Hz, 1H), 7.27–7.33 (m, 2H), 7.40 (dd, J=8.4, 10.4 Hz, 2H), 10.81 (s, 1H), 11.03 (d, J=1.7 Hz, 1H); 13C NMR: δ 178.4, 144.2, 137.7, 137.2, 131.5, 130.5, 130.4, 130.3, 126.6, 126.3, 125.9, 123.4, 121.5, 121.4, 120.6, 118.9, 112.1, 111.0, 110.3, 110.3, 109.1, 53.8, 32.9. HR-MS. Calcd for C25H19ClN3O+ ([M+H]+): m/z 412.1211. Found: m/z 412.1205.

5′-Chloro-1-methyl-1H,1″H-[3,3′:3′,3″-terindol]-2′(1′H)-one (3l)

This compound was obtained from 1g and 2a; yield 92%, 10 min, method A; yield 90%, 15 min, method B; off-white solid; mp 273–274°C; 1H NMR: δ 3.72 (s, 3H), 6.82–6.89 (m, 2H), 6.93 (s, 2H), 7.01–7.06 (m, 2H), 7.11 (dd, J=7.6, 7.1 Hz, 1H), 7.21–7.41 (m, 6H), 10.79 (s, 1H), 11.05 (s, 1H); 13C NMR: δ 178.8, 140.7, 137.9, 137.4, 137.0, 129.0, 128.4, 126.4, 126.0, 125.9, 125.2, 125.0, 121.7, 121.6, 121.4, 120.8, 119.0, 113.9, 113.2, 112.2, 111.6, 110.4, 53.2, 32.8. HR-MS. Calcd for C25H19ClN3O+ ([M+H]+): m/z 412.1211. Found: m/z 412.1210.

5′-Fluoro-1-methyl-1H,1″H-[3,3′:3′,3″-terindol]-2′(1′H)-one (3m)

This compound was obtained from 1h and 2a; yield 94%, 10 min, method A; yield 95%, 20 min, method B; off-white solid; mp 289–290°C (dec.); 1H NMR: δ 3.72 (s, 3H), 6.80–7.11 (m, 9H), 7.20 (d, J=7.5 Hz, 1H), 7.25 (d, J=7.6 Hz, 1H), 7.38 (dd, J=8.8, 8.5 Hz, 2H), 10.65 (bs, 1H), 11.02 (s, 1H); 13C NMR: δ 179.0, 158.3 (d, 1J(C−F) =235.3 Hz), 138.0 (d, 4J(C−F) =1.4 Hz), 137.8, 137.4, 136.7 (d, 3J(C−F) =7.6 Hz), 129.0, 126.4, 126.0, 125.0, 121.6, 121.5, 121.5, 120.8, 118.9, 118.9, 114.7 (d, 2J(C−F) =23.0 Hz), 114.1, 113.3, 112.9 (d, 2J(C−F) =24.3 Hz), 112.2, 110.9 (d, 3J(C−F) =8.0 Hz), 110.3, 53.5 (d, 4J(C−F) =1.2 Hz), 32.8. HR-MS. Calcd for C25H19FN3O+ ([M+H]+): m/z 396.1507. Found: m/z 396.1510.

1,5′-Dimethyl-1H,1″H-[3,3′:3′,3″-terindol]-2′(1′H)-one (3n)

This compound was obtained from 1i and 2a; yield 94%, 30 min, method A; yield 92%, 60 min, method B; off-white solid; mp 310–311°C (dec.); 1H NMR: δ 2.18 (s, 3H), 3.71 (s, 3H), 6.80–6.89 (m, 5H), 7.00–7.11 (m, 4H), 7.23–7.27 (m, 2H), 7.37 (dd, J=7.8, 7.8 Hz, 2H), 10.51 (s, 1H), 10.97 (s, 1H); 13C NMR: δ 179.1, 139.3, 137.8, 137.4, 135.1, 130.7, 128.9, 128.6, 126.6, 126.2, 125.9, 124.9, 121.7, 121.5, 121.4, 121.1, 118.8, 118.7, 114.8, 114.2, 112.1, 110.2, 109.8, 53.0, 32.8, 21.3. HR-MS. Calcd for C26H22N3O+ ([M+H]+): m/z 392.1757. Found: m/z 392.1755.

6′-Bromo-1-methyl-1H,1″H-[3,3′:3′,3″-terindol]-2′(1′H)-one (3o)

This compound was obtained from 1j and 2a; yield 92%, 20 min, method A; yield 90%, 45 min, method B; off-white solid; mp 285–286°C (dec.); 1H NMR: δ 3.71 (s, 3H), 6.80–6.88 (m, 4H), 7.02 (dd, J=6.7, 6.8 Hz, 1H), 7.08–7.16 (m, 4H), 7.19 (d, J=7.8 Hz, 1H), 7.24 (d, J=7.6 Hz, 1H), 7.34–7.40 (m, 2H), 10.72 (bs, 1H), 11.01 (s, 1H); 13C NMR: δ 179.0, 143.6, 137.8, 137.4, 134.3, 128.9, 127.2, 126.4, 126.0, 124.9, 124.6, 121.6, 121.5, 121.5, 120.8, 120.8, 118.9, 114.0, 113.3, 113.9, 112.2, 110.3, 52.7, 32.8. HR-MS. Calcd for C25H19BrN3O+ ([M+H]+): m/z 456.0706. Found: m/z 456.0701.

Acknowledgments

This work was supported by the Applied Basic Research Programs of Yunnan Science and Technology Department (2014FD039), the Foundation for Innovative Scientific Research Team of Kunming University (2015CXTD03), the Scientific Research Funds of Kunming University (XJL14016), and the Research Foundation for Introduced Talents of Kunming University (YJL15003).

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Received: 2016-5-11
Accepted: 2016-10-11
Published Online: 2017-1-28
Published in Print: 2017-2-1

©2017 Walter de Gruyter GmbH, Berlin/Boston

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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https://doi.org/10.1515/hc-2016-0071
Keywords for this article
alcohols; alkylation; C–C coupling; halogens; homogeneous catalysis
Creative Commons
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Articles in the same Issue

  1. Frontmatter
  2. Preliminary Communications
  3. Tandem hetero-Diels–Alder-hemiacetal reaction in the synthesis of new chromeno[4′,3′:4,5]thiopyrano[2,3-d]thiazoles
  4. A new method for the reaction of cross-coupling: preparation of 5,5′-bi(1,10-phenanthroline)
  5. Design and synthesis of 4,5-diaryl/heteroarylthiophene-2-carboxylic acid derivatives and evaluation of their biological activities
  6. Research Articles
  7. Synthesis and properties of dicarbazolyltriphenylethylene-substituted fluorene derivatives exhibiting aggregation-induced emission enhancement
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