HETEROCYCLES

Paper | Regular issue | Vol. 78, No. 8, 2009, pp. 2033-2040
Received, 13th March, 2009, Accepted, 9th April, 2009, Published online, 13th April, 2009.
DOI: 10.3987/COM-09-11706

■ Synthesis of Bis(indolyl)methane Derivatives by Acid-Catalyzed Reactions of Indoles with Vinyl Ethers

Kazuhiro Kobayashi,* Yuu Shirai, and Hisatoshi Konishi

Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan

Abstract

2,2-Bis(indol-3-yl)propane derivatives have been synthesized by the reaction of 3-nonsubstituted indoles with 2-methoxypropene in dichloromethane in the presence of a catalytic amount of (±)-camphor-10-sulfonic acid. The similar treatment of 3-substituted indoles with 2-methoxypropene under the same conditions has resulted in the formation of 2,2-bis(indol-2-yl)propanes. The reaction of 3-substituted indoles with ethoxyethene has afforded bis(indol-1- yl)ethanes. Subsequently, 3-substituted indoles have proved to react with excess vinyl ethers under the same conditions to afford the corresponding 1-(1-alkoxyalkyl)indoles.

INTRODUCTION
There has been substantial interest in bis(indol-3-yl)methane and its derivatives, because some of them have been reported to display a range of biological properties.1 These derivatives have been reported to be useful as highly selective colorimetric and ratiometric fluorescent molecular chemosensors for Cu2+ cations.2 Moreover, an elaboration of these derivatives to more complex molecules has been reported.3 Bis(indol-3-yl)methane derivatives have been synthesized by acid-catalyzed condensation of indoles with carbonyl compounds.4 Recently, a wide variety of catalysts have been reported to be useful for this condensation reaction.5 A one-pot preparation from 2-alkynylanilines using iron-palladium6a or gold6b catalysis systems has recently reported. In this paper we wish to demonstrate the results of our investigation on the reactions of indoles with vinyl ethers in the presence of a catalytic amount of an acid, which offer facile synthetic procedures for bis(indol-3-yl)methane, bis(indol-2-yl)methane,7 and bis(indol-1-yl)methane derivatives.8 We also present a synthesis of 3-substituted 1-(1- alkoxyalkyl)indoles from 3-substituted indoles and vinyl ethers.

RESULTS AND DISCUSSION
Bis(indol-3-yl)propanes (2a-c) were prepared from the respective 3-nonsubstituted indoles (1a-c) and 2-methoxypropene as shown in Scheme 1. It was found that when 1a-c were treated with 2-methoxypropene in the presence of a catalytic amount of (±)-camphor-10-sulfonic acid in dichloromethane at 0 ˚C, two to one condensation took place to lead to the desired products (2a-c) in the yields listed in Scheme 1. While condensation using indole (1a) and 5-bromoindole (1b) proceeded cleanly to give the corresponding bis(indol-3-yl)propanes (2a and 2b) in fair-to-good yields, the reaction using 2-methylindole (1c) gave a somewhat complicated mixture of products and the desired product (2c) was isolated in only low-to-moderate yield. This is probably attributable to the steric encumbrance due to the 2-methyl group. It should be noted that the reactions of indole (1a) with ethoxyethene or 1H-2,3-dihydropyran under the same conditions as described above resulted in the formation of intractable mixtures of products.

We anticipated that the use of excess 2-methoxypropene would be expected to afford 2,2-bis[1-(1-methoxy-1-methylethyl)indol-3-yl]propanes (3) by condensation of 3-nonsubstituted indoles with 2-methoxypropene accompanying N,N’-bis(1-methoxy-1-methylethylation), and the reactions were conducted as shown in Scheme 2. Thus, the mixture of 2,3-nonsubstituted indoles (1a, 1b, and 1d) and 3 molar amounts of 3-methoxypropene in dichloromethane was treated with a catalytic amount of (±)-camphor-10-sulfonic acid at 0 ˚C to result in the formation of 3 in good yields. In the case of using 2-methylindole (1c), N-(1-methoxy-1-methylethylation) did not occur. This is again presumed to be ascribed to the steric encumbrance due to the 2-methyl group.
Subsequently, the possibility of the preparation of N-(1-alkoxyalkylation) of 3-substituted indoles was examined. We found that the reactions of 3-substituted indoles (4a-c) with 3 molar amounts of vinyl ethers, such as 2-methoxypropene, 1H-2,3-dihydropyran, 2,3-dihydrofuran, and ethoxyethene, in the presence of a catalytic amount of (±)-camphor-10-sulfonic acid in dichloromethane under conditions indicated in Scheme 3 led to the formation of 1-(2-methoxypropyl)- (5a), 1-(tetrahydropyan-2-yl)- (5b), 1-(tetrahydrofuran-2-yl)- (5c), and 1-(1-ethoxylethyl)-indole derivatives (5d), respectively, in moderate- to-fair yields. While the reactions of 3-methylindole (4a) with 2-methoxypropene and 1H-2,3- dihydropyran producing 5a and 5b proceeded smoothly, the reaction of methyl indole-3-carboxylate (4b) with 2,3-dihydrofuran producing 5c required an elevated reaction temperature (room temperature) and a prolonged reaction time (6 d) and that of 2,3-dimethylindole (4c) with ethoxyethene producing 5d required a prolonged reaction time (10 h). These are possibly due to the lower reactivity of 4b and the steric encumbrance around the reaction center for 4c.

Scheme 4 shows that 2,2-bis(indol-2-yl)propanes (6) could be prepared by the treatment of 3-substituted indoles (4a) and (4d) with 2-methoxypropene in the presence of a catalytic amount of (±)-camphor-10- sulfonic acid in dichloromethane at room temperature, though the yields are low-to-moderate.
On the other hand, treatment of 3-substituted indoles (4a) and (4d) with ethoxyethene under conditions similar to those described for the preparation of 6 resulted in the formation of 1,1-bis(indol-1-yl)ethanes 7 in moderate yields, as shown in Scheme 5. Reason for the differences between the results using 2-methoxypropene and ethoxyethene can not be clarified.

In conclusion, we have demonstrated that the reactions of indoles with vinyl ethers, such as 2-methoxypropene and ethoxyethene, provide a new method for the construction of three types of bis(indolyl)methane structures. Studies are now in progress to investigate details of the reactions of indoles with vinyl ethers and related compounds.

EXPERIMENTAL
All melting points were obtained on a Laboratory Devices MEL-TEMP II melting apparatus and are uncorrected. IR spectra were determined with a Shimadzu FTIR-8300 spectrophotometer. The 1H NMR spectra were determined in CDCl3 using TMS as an internal reference with a JEOL ECP500 FT NMR spectrometer operating at 500 MHz. The 13C NMR spectra were determined in CDCl3 using TMS as an internal reference with a JEOL ECP500 FT NMR spectrometer operating at 125 MHz. Low- and high-resolution MS spectra (EI, 70 eV) were measured by a JEOL JMS AX505 HA spectrometer. TLC was carried out on a Merck Kieselgel 60 PF254. Column chromatography was performed using Merck Kieselgel 60 (0.063–0.200 mm). All of the organic solvents used in this study were dried over appropriate drying agents and distilled prior to use.
Starting Materials. All chemicals used in this study were commercially available.
1-Isocyano-2-propylbenzene. This compound was by treating 2-(lithiomethyl)phenyl isocyanide, generated according to the procedure reported by Ito et al.,9 with iodoethane in diglyme at –78 ˚C in 86% yield; a colorless liquid; bp 60–63 ˚C/1.45 mmHg; IR (neat) 2122 cm–1; 1H NMR δ 0.99 (t, J = 7.3 Hz, 3H), 1.69 (sext, J = 7.3 Hz, 2H), 2.74 (t, J = 7.3 Hz, 2H), 7.21 (ddd, J = 7.8, 7.3, 1.4 Hz, 1H), 7.26 (d, J = 7.8 Hz, 1H), 7.32 (ddd, J = 7.8, 7.3, 1.4 Hz, 1H), 7.34 (d, J = 7.8 Hz, 1H). MS m/z 145 (M+, 100). HR-MS Calcd for C10H11N: M, 145.0891. Found: m/z 145.0905.
3-Ethylindole (4d). This compound was prepared by treating the above isocyanide with lithium 2,2,6,6-tetrapiperidide in diglyme at –78 ˚C, followed by rising the reaction temperature to room temperature, according to the procedure reported by Ito et al.9 in 70% yield; a light brown solid; mp 36–37 ˚C (pentane) (lit.,10 37 ˚C); IR (KBr) 3055, 1618 cm–1; 1H NMR δ 1.34 (t, J = 7.3 Hz, 3H), 2.79 (qd, J = 7.3, 0.9 Hz, 2H), 6.98 (t, J = 0.9 Hz, 1H), 7.11 (ddd, J = 7.8, 7.3, 1.4 Hz, 1H), 7.19 (dd, J = 7.8, 7.3 Hz, 1H), 7.35 (d, J = 7.8 Hz, 1H), 7.62 (d, J = 7.8 Hz, 1H), 7.89 (br s, 1H).
Typical Procedure for the Preparation of 2,2-Bis(indol-3-yl)propanes (2). 3-[1-(Indol-3-yl)-1- methylethyl]indole (2a). To a stirred solution of indole (1a) (0.12 g, 1.0 mmol) and 2-methoxypropene (72 mg, 1.0 mmol) in CH2Cl2 (3 mL) at 0 ˚C was added (±)-camphor-10-sulfonic acid (12 mg, 0.050 mmol). After stirring had been continued for 30 min, saturated aqueous NaHCO3 (10 mL) and CH2Cl2 (10 mL) were added. The layers were separated, and the aqueous layer was extracted with CH2Cl2 three times (5 mL each). The combined extracts were washed with brine and dried over anhydrous Na2SO4. After evaporation of the solvent, the residue was purified by preparative TLC on silica gel (1:3 THF¬–hexane) to give 2a (98 mg, 73%); a white solid; mp 171¬–174 ˚C (hexane–Et2O) (lit.,11 175 ˚C ); IR (KBr) 3408, 3391, 1624 cm–1. The 1H NMR data for this product were identical to those reported previously.11
5-Bromo-3-[1-(5-bromoindol-3-yl)-1-methylethyl]indole (2b): mp 163–165 ˚C (lit.,12 165–166 ˚C). The spectral data (IR and IH NMR) were identical to those reported previously.12
2-Methyl-3-[1-methyl-1-(2-methylindol-3-yl)ethyl]indole (2c): mp 195–196 ˚C (hexane–CH2Cl2) (lit.,13 197 ˚C); IR (KBr) 3385 cm–1; 1H NMR δ 2.03 (s, 6H), 2.22 (s, 6H), 6.88 (ddd, J = 7.8, 7.3, 1.4 Hz, 2H), 7.02 (ddd, J = 8.2, 7.3, 0.9 Hz, 2H), 7.22 (d, J = 7.8 Hz, 2H), 7.49 (d, J = 8.2 Hz, 2H), 7.60 (br s, 2H).
Typical Procedure for the Preparation of N,N’-Bismethoxyalkylated 2,2-Bis(indol-3-yl)propanes (3). 1-(1-Methoxy-1-methylethyl)-3-{1-[1-(1-methoxy-1-methylethyl)indol-3-yl]-1-methylethyl}indole (3a). To a stirred solution of indole (1a) (0.12 g, 1.0 mmol) and 2-methoxypropene (0.22 g, 3.0 mmol) in CH2Cl2 (3 mL) at 0 ˚C was added (±)-camphor-10-sulfonic acid (12 mg, 0.050 mmol). After 10 min, the resulting mixture was worked up in a manner similar to that for the preparation of 2a. The residual solid was recrystallized from hexane–CH2Cl2 to give 3a (0.13 g, 60%); colorless needles; mp 173–176 ˚C; IR (KBr) 1609 cm–1; 1H NMR δ 1.84 (s, 12H), 1.88 (s, 6H), 3.05 (s, 6H), 6.82 (dd, J = 7.8, 7.3 Hz, 2H), 7.02 (s, 2H), 7.03 (dd, J = 7.8, 7.3 Hz, 2H), 7.32 (d, J = 7.8 Hz, 2H), 7.75 (d, J = 7.8 Hz, 2H); 13C NMR δ 26.53, 29.92, 34.71, 49.42, 88.66, 113.95, 118.42, 120.94, 121.01, 121.74, 123.94, 128.29, 136.45; MS m/z 418 (M+, 13), 354 (32), 339 (100). Anal. Calcd for C27H34N2O2: C, 77.48; H, 8.19; N, 6.69. Found: C, 77.37; H, 8.24; N, 6.60.
5-Bromo-3-{1-[5-bromo-1-(1-methoxy-1-methylethyl)indol-3-yl]-1-methylethyl}-1-(1-methoxy-1-methylethyl)indole (3b): colorless needles; mp 202–203 ˚C (hexane–CH2Cl2); IR (KBr) 1597 cm–1; 1H NMR δ 1.83 (s, 6H), 1.86 (s, 12H), 3.05 (s, 6H), 7.07 (dd, J = 8.7, 1.8 Hz, 2H), 7.23 (d, J = 1.8 Hz, 2H), 7.26 (s, 2H), 7.62 (d, J = 8.7 Hz, 2H); MS m/z 574 (M+, 7.2), 510 (27), 495 (100). Anal. Calcd for C27H32Br2N2O2: C, 56.26; H, 5.60; N, 4.86. Found: C, 56.13; H, 5.63; N, 4.84.
6-Chloro-3-{1-[6-chloro-1-(1-methoxy-1-methylethyl)indol-3-yl]-1-methylethyl}-1-(1-methoxy-1-methylethyl)indole (3d): colorless needles; mp 240–245 ˚C (hexane–CH2Cl2); IR (KBr) 1603 cm–1; 1H NMR δ 1.82 (s, 18H), 3.06 (s, 6H), 6.76 (dd, J = 8.7, 1.8 Hz, 2H), 7.01 (s, 2H), 7.08 (d, J = 8.7 Hz, 2H), 7.76 (d, J = 1.8 Hz, 2H); MS m/z 486 (M+, 10), 342 (42), 73 (100). Anal. Calcd for C27H32Cl2N2O2: C, 66.53; H, 6.62; N, 5.75. Found: C, 66.31; H, 6.50; N, 5.90.
Typical Procedure for the Preparation of N-Alkoxyalkylated Indoles (5). 1-(1-Methoxy-1- methylethyl)-3-methylindole (5a). To a stirred solution of 3-methylindole (4a) (0.13 g, 1.0 mmol) and 2-methoxypropene (0.22 g, 3.0 mmol) in CH2Cl2 (3 mL) at 0 ˚C was added (±)-camphor-10-sulfonic acid (12 mg, 0.050 mmol). After 30 min, the resulting mixture was worked up as described above. The residue was subjected to column chromatography on neutral alumina to give 5a (0.11 g, 54%); a pale-yellow oil; Rf 0.35 (hexane); IR (neat) 1610 cm–1; 1H NMR δ 1.80 (s, 6H), 2.31 (d, J = 0.9 Hz, 3H), 3.04 (s, 3H), 6.91 (s, 1H), 7.12 (ddd, J = 7.8, 7.3, 0.9 Hz, 1H), 7.18 (ddd, J = 7.8, 7.3, 1.4 Hz, 1H), 7.55 (d, J = 7.8 Hz, 1H), 7.78 (d, J = 7.8 Hz, 1H); MS m/z 203 (M+, 9.0) and 149 (100). Anal. Calcd for C13H17NO: C, 76.81; H, 8.43; N, 6.89. Found: C, 76.79; H, 8.53; N, 6.76.
3-Methyl-1-(tetrahydropyran-2-yl)-3-methylindole (5b): a pale-yellow oil; Rf 0.35 (1:19 Et2O–hexane); IR (neat) 1614 cm–1; 1H NMR δ 1.61–1.80 (m, 3H), 1.99–2.18 (m, 3H), 2.31 (d, J = 0.9 Hz, 3H), 3.73 (td, J = 11.5, 2.3 Hz, 1H), 4.09 (dt, J = 11.5, 1.8 Hz, 1H), 5.45 (dd, J = 10.1, 2.3 Hz, 1H), 7.08 (s, 1H), 7.12 (dd, J = 7.8, 7.3 Hz, 1H), 7.21 (dd, J = 7.8, 7.3 Hz, 1H), 7.41 (d, J = 7.8 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H); MS m/z 216 [(M+1)+, 42], 131 (100). Anal. Calcd for C14H17NO: C, 78.10; H, 7.96; N, 6.51. Found: C, 78.08; H, 8.12; N, 6.38.
Methyl 1-(Tetrahydrofuran-2-yl)indole-3-carboxylate (5c): for 6 d at rt; a pale-yellow oil; Rf 0.21 (1:2 CH2Cl2–hexane); IR (neat) 1695, 1614 cm–1; 1H NMR δ 2.12–2.17 (m, 2H), 2.38–2.49 (m, 2H), 3.91 (s, 3H), 4.05 (dt, J = 8.2, 7.3 Hz, 1H), 4.21 (ddd, 8.2, 6.4, 1.8 Hz, 1H), 6.24 (dd, J = 6.6, 3.2 Hz, 1H), 7.28 (t, J = 6.5 Hz, 1H), 7.30 (t, J = 6.5 Hz, 1H), 7.45 (dd, J = 6.5, 2.7 Hz, 1H), 7.95 (s, 1H), 8.17 (dd, J = 6.5, 2.7 Hz, 1H); 13C NMR δ 24.21, 32.08, 51.01, 69.00, 86.29, 107.57, 110.51, 121.76, 122.19, 122.90, 127.09, 130.66, 135.62, 165.54; MS m/z 245 (M+, 40), 175 (100). Anal. Calcd for C14H15NO3: C, 68.56; H, 6.16; N, 5.71. Found: C, 68.41; H, 6.31; N, 5.60.
1-(1-Ethoxyethyl)-2,3-dimethylindole (5d): for 10 h at 0 ˚C; a pale-yellow oil; Rf 0.54 (1:19 Et2O– hexane); IR (neat) 1614 cm–1; 1H NMR δ 1.15 (t, J = 7.3 Hz, 3H), 1.69 (d, J = 6.0 Hz, 3H), 2.23 (s, 3H), 2.40 (s, 3H), 3.24–3.38 (m, 2H), 5.67 (q, J = 6.0 Hz, 1H), 7.08 (td, J = 7.3, 1.4 Hz, 1H), 7.12 (ddd, J = 7.8, 7.3, 1.4 Hz, 1H), 7.47 (dd, J = 7.3, 1.4 Hz, 1H), 7.56 (d, J = 7.8 Hz, 1H); MS m/z 217 (M+, 3.2), 172 (100). Anal. Calcd for C14H19NO: C, 77.38; H, 8.81; N, 6.45. Found: C, 77.30; H, 8.90; N, 6.50.
Typical Procedure for the Preparation of 2,2-Bis(indol-2-yl)propanes (6). 3-Methyl-2-[1-methyl-1- (3-methylindol-2-yl)ethyl]indole (6a). To a stirred solution of 3-methylindole (4a) (0.13 g, 1.0 mmol) and 2-methoxypropene (72 mg, 1.0 mmol) in CH2Cl2 (3 mL) at rt was added (±)-camphor-10-sulfonic acid (12 mg, 0.050 mmol). After stirring overnight, the resulting mixture was worked up as described above. The resulting residue was purified by preparative TLC on silica gel to give 6 (64 mg, 42%); a yellow viscous oil; Rf 0.17 (1:9 THF–hexane); IR (neat) 3439, 1615 cm–1; 1H NMR δ 1.91 (s, 6H), 2.11 (s, 6H), 7.11 (ddd, J = 7.8, 7.3, 0.9 Hz, 2H), 7.16 (ddd, J = 7.8, 7.3, 1.4 Hz, 2H), 7.29 (d, J = 7.8 Hz, 2H), 7.52 (d, J = 7.8 Hz, 2H), 7.89 (br s, 2H); 13C NMR δ 9.40, 28.11, 37.41, 106.94, 110.51, 118.12, 119.19, 121.42, 130.18, 134.06, 139.02; MS m/z 302 (M+, 100). Anal. Calcd for C21H22N2: C, 83.40; H, 7.33; N, 9.26. Found: C, 83.55; H, 7.96; N, 8.25.
3-Ethyl-2-[1-(3-ethylindol-2-yl)-1-methylethyl]indole (6d): a yellow viscous oil; Rf 0.22 (1:4 Et2O–hexane); IR (neat) 3420, 1615 cm–1; 1H NMR δ 1.15 (t, J = 7.3 Hz, 6H), 1.93 (s, 6H), 2.62 (q, J = 7.3 Hz, 4H), 7.10 (ddd, J = 7.8, 7.3, 1.4 Hz, 2H), 7.15 (ddd, J = 7.8, 7.3, 1.4 Hz, 2H), 7.28 (d, J = 7.8 Hz, 2H), 7.56 (d, J = 7.8 Hz, 2H), 7.83 (br s, 2H); MS m/z 330 (M+, 100). Anal. Calcd for C23H26N2: C, 83.59; H, 7.93; N, 8.48. Found: C, 83.11; H, 7.50; N, 9.29.
Typical Procedure for the Preparation of 1,1-Bis(indol-1-yl)ethanes (7). 3-Methyl-1-[1-(3- methylindol-1-yl)ethyl]indole (7a). To a stirred solution of 3-methylindole (4a) (0.13 g, 1.0 mmol) and ethyl vinyl ether (72 mg, 1.0 mmol) in CH2Cl2 (3 mL) at rt was added (±)-camphor-10-sulfonic acid (12 mg, 0.050 mmol). After 10 min, the resulting mixture was worked up as described above. The resulting residue was purified by preparative TLC on silica gel to give 7a (89 mg, 62%); a yellow viscous oil; Rf 0.31 (1:19 Et2O–hexane); IR (neat) 1614 cm–1; 1H NMR δ 2.08 (d, J = 6.9 Hz, 3H), 2.29 (d, J = 0.9 Hz, 6H), 6.82 (q, J = 6.9 Hz, 1H), 6.97 (s, 2H), 7.11 (ddd, J = 7.8, 7.3, 0.9 Hz, 2H), 7.16 (ddd, J = 7.8, 7.3, 0.9 Hz, 2H), 7.29 (d, J = 7.8 Hz, 2H), 7.55 (d, J = 7.8 Hz, 2H); 13C NMR δ 9.74, 20.87, 62.10, 109.22, 111.98, 119.21, 119.48, 121.80, 122.13, 129.29, 135.78; MS m/z 288 (M+, 18), 158 (100). Anal. Calcd for C20H20N2: C, 83.30; H, 6.99; N, 9.71. Found: C, 83.15; H, 6.99; N, 9.64.
3-Ethyl-1-[1-(3-ethylindol-1-yl)ethyl]indole (7d): a yellow viscous oil; Rf 0.50 (1:19 Et2O–hexane); IR (neat) 1611 cm–1; 1H NMR δ 1.30 (t, J = 7.3 Hz, 6H), 2.08 (d, J = 6.9 Hz, 3H), 2.75 (qd, J = 7.3, 0.9 Hz, 4H), 6.81 (q, J = 6.9 Hz, 1H), 6.97 (s, 2H), 7.10 (dd, J = 7.8, 7.3 Hz, 2H), 7.16 (dd, J = 7.8, 7.3 Hz, 2H), 7.29 (d, J = 7.8 Hz, 2H), 7.58 (d, J = 7.8 Hz, 2H); MS m/z (%) 316 (M+, 14), 172 (100). Anal. Calcd for C22H24N2: C, 83.50; H, 7.64; N, 8.85. Found: C, 83.40; H, 7.72; N, 8.79.

ACKNOWLEDGEMENTS
We wish to express our appreciation to Mrs. Miyuki Tanmatsu of this University for her support in determining mass spectra and performing combustion analysis.

References

1. For recent reports, see (a) D. Kong, Y. Li, Z. Wang, and S. Banerjee, Cancer Res., 2007, 67, 3310; CrossRef (b) C. Pal, S. Dey, S. K. Mahato, J. Vinayagam, P. K. Pradhan, V. S. Giri, P. Jaisankar, T. Hossain, S. Baruri, D. Ray, and S. M. Biswas, Bioorg. Med. Chem. Lett., 2007, 17, 4924; CrossRef (c) F. H. Sarkar, Y. Li, Z. Wang, D. Kong, S. Murthy, Q. P. Dou, S. Sheng, G. P. V. Reddy, and F. H. Sarkar, J. Biol. Chem., 2007, 282, 21542; CrossRef (d) L. Xue, J. J. Pesrtka, M. Li, G. L. Firestone, and L. F. Bjeldanes, J. Nutrition. Biochem., 2008, 19, 336; CrossRef (e) J. E. Riby, G. L. Friestone, and L. F. Bjeldanes, Biochem. Pharmacol., 2008, 75, 1858; CrossRef (f) D. Kong, S. Banerjee, W. Huang, Y. Li, Z. Wang, H.-R. C. Kim, and F. H. Sarkar, Cancer Res., 2008, 68, 1927. CrossRef
2. R. Martinez, A. Espinosa, A. Tarraga, and P. Molina, Tetrahedron, 2008, 64, 2184. CrossRef
3. M. L. Deb and P. J. Bhuyan, Synlett, 2008, 325. CrossRef
4. J. Thesing, S. Klussendorf, P. Balach, and H. Mayer, Chem. Ber., 1955, 88, 1295. CrossRef
5. Recent reports on the preparation of bis(indol-3-yl)methane derivatives: (a) H. Hagiwara, M. Sekifuji, T. Hoshi, K. Qiao, and C. Yokoyama, Synlett, 2007, 1320; CrossRef (b) A. Srinivasa, B. P. Nandeshwarappa, B. M. Kiran, and K. M. Mahadevan, Phosphorous, Sulfur Silicon Relat. Elem., 2007, 182, 2243; CrossRef (c) S. Podder, J. Choudhury, U. K. Roy, and S. Roy, J. Org. Chem., 2007, 72, 3100; CrossRef (d) B.-S. Liao, J.-T. Chen, and S.-T. Liu, Synthesis, 2007, 3125; CrossRef (e) A. Khalafi-Nezhad, A. Parthmi, A. Zare, A. R. M. Zare, A. Hasaninejad, and F. Panahi, Synthesis, 2008, 617; CrossRef (f) M. Hosseini-Sarvari, Synth. Commun., 2008, 38, 832; CrossRef (g) S.-Y. Wang and S.-J. Ji, Synth. Commun., 2008, 38, 1291; CrossRef (h) J. J. P. Selvam, M. Srinivasulu, N. Suryakiran, V. Suresh, S. M. Reddy, and Y. Venkateswarlu, Synth. Commun., 2008, 38, 1760; CrossRef (i) M. L. Deb and P. J. Bhuyan, Synthesis, 2008, 2891; CrossRef (j) A. Zare, A. Parhami, A. R. Moosavi-Zare, A. Hasaninejad, A. Khalafi-Nezhad, and H. Mohammad, Can. J. Chem., 2009, 87, 416. CrossRef
6. (a) V. Terrasson, J. Michaux, A. Gaucher, J. Wehbe, S. Marque, D. Prim, and J.-M. Campagne, Eur. J. Org. Chem., 2007, 5332; CrossRef (b) C. Praveen, Y. W. Sagayaraj, and P. T. Perumal, Tetrahedron Lett., 2009, 50, 644. CrossRef
7. For previous syntheses of bis(indol-2-yl)methane derivatives, see M. Chakrabarty, A. Mukherji, S. Karmakar, S. Arima, and Y. Harigaya, Heterocycles, 2006, 68, 331 and refs cited in this paper. CrossRef
8. For previous syntheses of bis(indol-1-yl)methane derivatives, see C. Gonzalez and R. R. Greenhouse, Heterocycles, 1985, 23, 1127 and refs cited in this paper. CrossRef
9. Y. Ito, K. Kobayashi, N. Seko, and T. Saegusa, Bull. Chem. Soc. Jpn., 1984, 57, 73. CrossRef
10. R. Odel, B. Blevins, M. Ratcliff, and L. S. Hegedus, J. Org. Chem., 1980, 45, 2709. CrossRef
11. J.-T. Li, H.-G. Dai, W.-Z. Xu, and T.-S. Li, Ultrason. Sonochem., 2006, 13, 24. CrossRef
12. J. Bergman, P.-O. Norrby, U. Tilstam, and L. Venemalm, Tetrahedron, 1989, 45, 5549. CrossRef
13. B. Oddo and L. Perotti, Gazz. Chim. Ital., 1930, 60, 13