HETEROCYCLES

Paper | Special issue | Vol. 86, No. 1, 2012, pp. 505-513
Received, 22nd June, 2012, Accepted, 2nd August, 2012, Published online, 13th August, 2012.
DOI: 10.3987/COM-12-S(N)49

■ SHORT APPROACH TO BISINDOLE ALKALOID, YUEHCHUKENE, USING 2-INDOLYLCYANOCUPRATE

Takumi Abe, Hiroyuki Komatsu, Toshiaki Ikeda, Noriyuki Hatae, Eiko Toyota, and Minoru Ishikura*

Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan

Abstract

A short total synthesis of a bisindole alkaloid, yuechukene, was achieved through the dimerization of β-dehydroprenylindole generated in situ from 1-(indol-3yl)-3-methylbut-2-en-1-amine.

INTRODUCTION
A novel bisindole alkaloid, yuehchukene (1), was first isolated from the root of Murraya paniculata (L.) Jack in racemic form, and the structure was characterized as a dimer of β-dehydroprenylindole (2) based on both spectral analysis and X-ray crystallography (Figure 1).1 Yuehchukene (1) exhibits strong anti-implantation activity in rats as well as mice.2 Additionally, a combination of cyclophosphamide and 1 provides a fairly strong cytotoxic effect on the MCR-7 cell line when compared with cyclophosphamide alone.3 Owing to the potential biological activities of 1, it is an attractive target for synthesis.4 We previously reported the total synthesis of 1 with the key step being a palladium-catalyzed carbonylative cross-coupling reaction of triethyl(indol-2-yl)borate.5 The hypothesis6 that 1 is the biogenetic product of the dimerization of 2 has prompted the development of biomimetic approach using 1-(indol-3-yl)-3-methylbut-2-en-1-ol or 4-(indol-3-yl)-2-methylbut-3-en-2-ol as the key precursor of 2 under neutral conitions or acid catalysis.7 In connection with our continuing interest in synthetic application of 2-indolylcyanocuprate 4, we previously reported the regioselective construction of 2,3-disubstituted indoles through the reaction of 2-indolylcyanocuprate 4 with electrophiles in a one-pot procedure.8 It was envisioned that 1-(indol-3-yl)-3-methylbut-2-en-1-amine 7, regioselectively obtainable by the reaction of 4 with iminium 6,8a could serve as a useful synthetic equivalent of 2.9 In this paper, we describe a short total synthesis of yuehchukene (1) through the dimerization of 7.

RESULTS AND DISCUSSION

Our initial attempts to obtain the 3-substituted indole 7 through the reaction of 6 (derived from imine 5 and ClCO2Ph) with indole or indolyl anion (generated by treating indole with NaH in THF) were unsuccessful, resulting in only the recovery of indole or the formation of a complex mixture of products. As a result, the reaction of 4 (generated in situ from indole 3 and tert- or n-BuLi in THF, followed by treatment with CuCN at -20 °C) with iminium 6 was undertaken by way of a one-pot procedure.8a The reaction was carried out through slow addition of an acyl chloride to a pre-mixed solution of 4 and 5 in THF in the presence of HMPA at -20 °C, resulting in the formation of two types of products 1,2-adduct 7 and 1,4-adduct 8 (Scheme 1 and Table 1).10 After screening various acyl chlorides (X-Cl), in the reaction of 4a with 5, ClCO2Ph was found to give 7d in the highest yield (65%) along with 8d in 14% yield (Entry 4). Furthermore, reacting 4b with 5 by adding ClCO2Ph afforded 7e in 60% and 8e in 12% yields (Entry 6). However, performing the reaction of 4a with 5 in the presence of i-Pr2NEt and HMPA using ClCO2Ph at -20 °C lowered the yield of 7d to 30% (Entry 5). This was ascribed to the facile generation of dienamine 9 from 6 (X = CO2Ph) via deprotonation/isomerization, which was enhanced by the presence of i-Pr2NEt.8a No reaction was observed between 4c and 5 when using ClCO2Ph (Entry 7).

Next, we turned our attention to the dimerization of 7d (Table 2). Initially, 7d was simply heated in ethylene glycol at 150 °C, but no isolable products were obtained (Entry 1). Heating 7d in the presence of 2 equiv of TFA and AcOH in ethylene glycol at 150 °C resulted in the formation of a complex mixture of products (Entries 2 and 3), whereas treating 7d with TMSCl (2 equiv) in CH2Cl2 at room temperature produced N,N’-dimethylyuehchukene 13, but in only low yield (~10%) (Entry 6). After performing the dimerization reaction under various conditions, using TMSCl (2 equiv) in DME in pre-heated oil bath at 100 °C was found to provide 13 in 20% yield (Entry 7). The highest yield of 13 (35%) was obtained through the slow addition of a DME solution of TMSCl (1 equiv) to a refluxing solution of 7d in DME (Entry 8).

The dimerization reaction is presumed to proceed by the in situ generation of diene 10 and its dienophilic tautomer 11 from 7d, the subsequent Diels-Alder reaction between 10 and 11, followed by the intramolecular cyclization of 12 to 13 (Scheme 2).6

After having found suitable conditions for the dimerization of 7d, 7e was subjected to the dimerization in a similar manner. After a solution of TMSCl (1 equiv) was added dropwise to a solution of 7e at 100 °C, the mixture was heated at 100 °C for an additional 16 h, producing yuehchukene (1) in 30% yield (Scheme 3).11

In summary, we have developed a short total synthesis of N,N’-dimethylyuehchukene (13) and yuehchukene (1) from the corresponding indoles 3a and 3b via 2-indolylcyanocuprates 4a and 4b. We are currently investigating further application of 2-indolylcyanocuprates 4 in the synthesis of other indole alkaloids.

EXPERIMENTAL
Melting points were recorded on a Yamato MP21 and are uncorrected. HR-ESI-MS spectra were recorded on a JEOL JMS-T100LP mass spectrometer, and HR-EI-MS spectra were recorded on a Micromass AutoSpec 3100 mass spectrometer. IR spectra were measured on a Shimadzu IRAffinity-1 FT-IR spectrophotometer. The NMR experiments were performed with a JEOL JNM-ECA500 (500 MHz) spectrometer, and chemical shifts are expressed in ppm (δ) with TMS as an internal reference. Column chromatography was performed on silica gel (Silica Gel 60N, Kanto Chemical Co., Ltd.).
General procedure for the reaction of 4a with 5 using acyl chloride (X-Cl): tert-BuLi (1.6 M in pentane, 1.5 mL, 2.4 mmol) was added to a solution of 1-methylindole (3a) (262 mg, 2 mmol) in THF (30 mL) at 0 °C under an argon atmosphere, and the mixture was stirred at room temperature for 1 h. After the mixture was cooled to -20 °C, CuCN (214 mg, 2.4 mmol) was added to the mixture at -20 °C, and the mixture was stirred for 30 min. After HMPA (1 mL) and imine 5 (519 mg, 3 mmol) were added, acyl chloride (X-Cl) (3 mmol) was added slowly to the mixture. The reaction mixture was gradually warmed to room temperature and stirred overnight. The mixture was diluted with AcOEt (200 mL), washed with brine and dried over MgSO4. The solvent was removed, and the residue was separated by silica gel column chromatography with hexane/AcOEt (15:1) to give 7 and 8 (Table 1).
N-Benzyl-N-[3-methyl-1-(1-methyl-1H-indol-3-yl)but-2-en-1-yl]acetamide (7a): IR (CHCl3): 1622 cm–1. 1H-NMR (CDCl3) δ: 1.70 (s, 3H), 1.85 (s, 3H), 1.99 (s, 3H), 3.74 (s, 3H), 4.33 (d, 1H, J = 17.8 Hz), 4.41 (d, 1H, J = 18.4 Hz), 5.45 (d, 1H, J = 9.8 Hz), 6.90 (s, 1H), 7.04–7.29 (m, 9H), 7.66 (d, 1H, J = 8.0 Hz). 13C-NMR (CDCl3) δ: 18.9, 22.6, 25.8, 32.9, 48.1, 48.2, 109.3, 114.6, 119.6, 120.1, 122.0, 122.1, 126.1, 126.8, 127.8, 127.9, 128.2, 128.4, 136.4, 137.5, 139.0, 170.1. HR-EI-MS m/z: Calcd for C23H26N2O (M+): 346.2045. Found: 346.2045.
N-Benzyl-N-[(1E)-3-methyl-3-(1-methyl-1H-indol-3-yl)but-1-en-1-yl]acetamide (8a): IR (CHCl3): 1638 cm–1. 1H-NMR (CDCl3) δ: 1.45 (s, 3H), 1.56 (s, 3H), 2.10 (s, 3H), 3.66 (s, 3H), 4.89 (s, 2H), 5.38 (d, 1H, J = 14.4 Hz), 6.44 (d, 1H, J = 14.4 Hz), 7.02 (d, 1H, J = 8.0 Hz), 7.14–7.31 (m, 8H), 7.51 (d, 1H, J = 8.0 Hz). 13C-NMR (CDCl3) δ: 22.2, 29.1, 29.5, 32.6, 36.0, 46.5, 109.4, 118.5, 121.3, 121.4, 122.3, 124.8, 125.4, 125.9, 127.0, 127.3, 128.5, 128.9, 137.5, 137.8, 169.8. HR-EI-MS m/z: Calcd for C23H26N2O (M+): 346.2045. Found: 346.2041.
N-Benzyl-N-[3-methyl-1-(1-methyl-1H-indol-3-yl)but-2-en-1-yl]benzamide (7b): IR (CHCl3): 1620 cm–1. 1H-NMR (CDCl3) δ: 1.71 (s, 3H), 1.82 (s, 3H), 3.60 (s, 3H), 4.46 (s, 1H), 4.49 (s, 1H), 5.33 (d, 1H, J = 14.9 Hz), 5.56 (br s, 1H), 6.40 (br s, 1H), 7.00–7.45 (m, 13H), 7.71 (br s, 1H). 13C-NMR (CDCl3) δ: 19.6, 25.6, 42.4, 47.9, 50.2, 112.4, 117.6, 119.0, 126.5, 127.1, 127.2, 128.0, 128.6, 131.9, 135.2, 136.5, 169.5. HR-EI-MS m/z: Calcd for C28H28N2O (M+): 408.2202. Found: 408.2199.
N-Benzyl-N-[(1E)-3-methyl-3-(1-methyl-1H-indol-3-yl)but-1-en-1-yl]benzamide (8b): IR (CHCl3): 1638 cm–1. 1H-NMR (CDCl3) δ: 1.49 (s, 6H), 3.65 (s, 3H), 4.80 (s, 2H), 5.13 (d, 1H, J = 14.4 Hz), 6.35 (d, 1H, J = 14.4 Hz), 7.05 (d, 1H, J = 8.0 Hz), 7.15-7.37 (m, 13H), 7.54 (d, 1H, J = 8.0 Hz). 13C-NMR (CDCl3) δ: 32.1, 32.3, 42.4, 48.4, 49.3, 111.1, 116.2, 119.0, 120.1, 122.2, 122.3, 126.3, 126.5, 126.6, 126.8, 127.0, 127.1, 127.5, 127.8, 128.5, 128.6, 128.9, 132.2, 134.2, 137.6, 141.7, 169.3. HR-EI-MS m/z: Calcd for C23H26N2O (M+): 346.2045. Found: 346.2041.
Methyl Benzyl[3-methyl-1-(1-methyl-1H-indol-3-yl)but-2-en-1-yl]carbamate (7c): IR (CHCl3): 1680 cm–1. 1H-NMR (CDCl3) δ: 1.68 (s, 3H), 1.75 (s, 3H), 3.74 (s, 3H), 3.78 (br s, 3H), 4.15 (s, 1H), 4.18 (s, 1H), 4.51 (br s, 1H), 5.46 (d, 1H, J = 9.2 Hz), 6.52 (br s, 1H), 6.87 (br s, 1H), 7.06–7.30 (m, 8H), 7.62 (br s, 1H). 13C-NMR (CDCl3) δ: 14.3, 18.5, 25.8, 32.9, 47.0, 51.4, 52.8, 60.5, 109.3, 114.4, 119.5, 119.9, 122.1, 122.9, 126.4, 127.1, 128.0, 135.5, 137.5, 140.0, 157.3. HR-EI-MS m/z: Calcd for C23H26N2O2 (M+): 362.1994. Found: 362.1989.
Methyl Benzyl[(1E)-3-methyl-3-(1-methyl-1H-indol-3-yl)but-1-en-1-yl]carbamate (8c): IR (CHCl3): 1686 cm–1. 1H-NMR (CDCl3) δ: 1.41 (s, 6H), 3.65 (s, 3H), 3.71 (br s, 3H), 4.82 (br d, 2H, J = 12.1 Hz), 5.27 (d, 1H, J = 14.9 Hz), 6.60, 6.65(two br s, 1H), 6.89–7.31(m, 9H), 7.49 (d, 1H, J = 8.0 Hz). 13C-NMR (CDCl3) δ: 18.9, 22.6, 25.8, 32.9, 48.1, 48.2, 109.3, 114.6, 119.6, 120.1, 122.0, 122.1, 126.1, 126.8, 127.8, 127.9, 128.2, 128.4, 136.4, 137.5, 139.0, 170.1. HR-EI-MS m/z: Calcd for C28H26N2O2 (M+): 362.1994. Found: 362.1989.
Phenyl Benzyl[3-methyl-1-(1-methyl-1H-indol-3-yl)but-2-en-1-yl]carbamate (7d): IR (CHCl3): 1702 cm–1. 1H-NMR (CDCl3) δ: 1.71 (s, 3H), 1.77 (s, 3H), 3.76 (s, 3H), 4.31 (m, 1H), 4.61 (d, 1H, J = 16.1 Hz), 5.56 (d, 1H, J = 8.6 Hz), 6.58 (br s, 1H), 6.90–7.41 (m, 14H), 7.73 (br s, 1H). 13C-NMR (CDCl3) δ: 18.6, 25.8, 32.9, 47.4, 51.6, 109.4, 114.1, 119.6, 119.9, 121.9, 122.1, 125.2, 126.6, 127.1, 128.1, 129.3, 136.3, 137.5, 139.7, 151.6, 155.1. HR-EI-MS m/z: Calcd for C28H28N2O2 (M+): 424.2151. Found: 424.2149.
Phenyl Benzyl[(1E)-3-methyl-3-(1-methyl-1H-indol-3-yl)but-1-en-1-yl]carbamate (8d): IR (CHCl3): 1716 cm–1. 1H-NMR (CDCl3) δ: 1.51 (s, 6H), 3.65 (s, 3H), 4.91, 4.95 (two s, 2H), 5.40 (d, 1H, J = 15.0 Hz) 6.42, 6.52 (two s, 1H), 7.00–7.43 (m, 14H), 7.61 (d, 1H, J = 8.0 Hz). 13C-NMR (CDCl3) δ: 29.2, 32.6, 35.8, 48.4, 109.4, 118.5, 121.2, 121.3, 121.8, 121.9, 123.0, 123.2, 124.2, 125.0, 125.1, 125.7, 126.6, 127.2, 127.3, 128.7, 129.4, 137.2, 137.8, 151.2, 151.4, 153.3. HR-EI-MS m/z: Calcd for C28H28N2O2 (M+): 424.2151. Found: 424.2145.
Reaction of 4b with 5 using ClCO2Ph: n-BuLi (1.6 M in hexane, 1.5 mL, 2.4 mmol) was added to a solution of 1-methoxyindole (3b) (294 mg, 2 mmol) in THF (30 mL) at -20 °C under an argon atmosphere, and the mixture was stirred for 30 min. Then, CuCN (214 mg, 2.4 mmol) was added to the mixture at -20 °C and the whole was stirred for 30 min. After HMPA (1 mL) and imine 5 (519 mg, 3 mmol) were added to the mixture at -20 °C, ClCO2Ph (468 mg, 3 mmol) was added slowly. The mixture was gradually warmed to room temperature and stirred overnight. The mixture was diluted with AcOEt (200 mL), washed with brine and dried over MgSO4. After the solvent was removed, the residue was separated by silica gel column chromatography with hexane/AcOEt (15:1) to give 7e and 8e (Table 1).
Phenyl Benzyl[1-(1-methoxy-1H-indol-3-yl)-3-methylbut-2-en-1-yl]carbamate (7e): a pale yellow oil. IR (neat): 1714, 1699, 1595 cm-1. 1H-NMR (CDCl3) δ: 1.72, 1.77 (two s, 6H), 4.04 (s, 3H), 4.32 (d, 1H, J = 15.0 Hz), 4.60 (d, 1H, J = 15.0 Hz), 5.53 (d, 1H, J = 9 Hz), 6.43-6.62 (m, 0.5 H), 6.90-7.05 (m, 1H), 7.10-7.23 (m, 10H), 7.23-7.39 (m, 3H), 7.41 (d, 1H, J = 9 Hz), 7.60-7.76 (m, 0.5H). 13C-NMR (CDCl3) δ: 18.6, 25.8, 47.4, 51.3, 65.9, 108.4, 111.5, 120.1, 120.3, 121.8, 122.4, 122.9, 125.3, 126.6, 126.8, 128.1, 129.3, 132.8, 136.9, 139.4, 151.5, 155.0. HR-ESI-MS m/z: Calcd for C28H28N2O3Na [(M+Na)+]: 463.1998. Found: 463.2008.
Phenyl Benzyl[(1E)-3-(1-methoxy-1H-indol-3-yl)-3-methylbut-1-en-1-yl]carbamate (8e): a pale yellow oil. IR (neat): 1714, 1660 cm-1. 1H-NMR (CDCl3) δ: 1.48, 1.54 (two s, 6H), 4.00 (s, 3H), 4.90 (s, 1H), 4.93 (s, 1H), 5.36 (d, 1H, J = 14.8 Hz), 6.66, 6.75 (two s, 1H), 6.90-7.09 (m, 2H), 7.10-7.24 (m, 2H), 7.30-7.40 (m, 10H) 7.56 (d, 1H, J = 7.3 Hz). 13C-NMR (CDCl3) δ: 29.1, 35.9, 48.4, 65.5, 108.4, 119.2, 119.4, 119.5, 120.6, 120.8, 121.4, 121.7, 122.0, 122.1, 122.2, 122.5, 122.7, 124.4, 125.2, 125.7, 126.5, 127.2, 127.3, 128.7, 129.4, 133.5, 137.1, 151.1, 151.3, 153.2, 153.3. HR-ESI-MS m/z: Calcd for C28H28N2O3Na [(M+Na)+]: 463.1998. Found: 463.1996.
N,N’-Dimethylyuehchukene (13): To a solution of 7d (110 mg, 0.26 mmol) in DME (30 mL) at 100 °C under an argon atmosphere, a solution of TMSCl (33 µL, 0.26 mmol) in DME (100 µL) was added dropwise over 10 min, and the mixture was heated at 100 °C for 16 h. After cooling, the mixture was diluted with AcOEt (200 mL), washed with 10% aq. NaHCO3 solution and brine, and dried over MgSO4. The solvent was removed and the residue was separated by silica gel column chromatography with hexane/AcOEt (7:1) to give 13 (35 mg, 35%) as a pale yellow oil. IR (CHCl3): 3007, 2957, 2928 cm-1. 1H-NMR (CDCl3) δ: 0.83 (s, 3H), 1.08 (s, 3H), 1.62 (d, 1H, J = 17.2 Hz), 1.64 (s, 3H), 2.19 (d, 1H, J = 17.2 Hz), 3.06 (t, 1H, J = 6.9 Hz), 3.11 (s, 3H), 3.76 (s, 3H), 4.02 (d, 1H, J = 4.6 Hz), 4.56 (d, 1H, J = 7.5 Hz), 5.71 (s, 1H), 6.88 (s, 1H), 7.00 (t, 1H, J = 7.4 Hz), 7.07-7.10 (m, 2H), 7.13 (m, 1H), 7.20 (t, 1H, J = 7.5 Hz), 7.29 (d, 1H, J = 8.6 Hz), 7.40 (d, 1H, J = 8.1 Hz), 7.58 (dd, 1H, J = 3.4, 6.3 Hz). 13C-NMR (CDCl3) δ: 24.2, 28.5, 29.2, 29.9, 32.8, 33.6, 37.2, 38.4, 41.5, 62.5, 109.3, 109.5, 117.7, 118.4, 118.9, 119.0, 119.3, 119.6, 119.9, 121.5, 123.1, 123.5, 127.2, 127.3, 130.3, 137.2, 141.2, 146.3. HR-ESI-MS m/z: Calcd for C28H31N2 [(M+H)+]: 395.248. Found: 395.2481.
Yuehchukene (1): To a solution of 7e (125 mg, 0.28 mmol) in DME (30 mL) at 100 °C under an argon atmosphere, a solution of TMSCl (36 µL, 0.28 mmol) in DME (100 µL) was added dropwise over 10 min, and the mixture was heated at 100 °C for 16 h. After cooling, the mixture was diluted with AcOEt (200 mL), washed with 10% aq. NaHCO3 solution and brine, and dried over MgSO4. The solvent was removed and the residue was separated by silica gel column chromatography with hexane/AcOEt (4:1) to give 1 (31 mg, 30%) as amorphous powders. IR (CHCl3): 3476, 3422, 3009 cm-1. 1H-NMR (CDCl3) δ: 0.86 (s, 3H), 1.09 (s, 3H), 1.62 (d, 1H, J = 17.7 Hz), 1.66 (s, 3H), 2.28 (d, 1H, J = 17.7 Hz), 3.16 (t, 1H, J = 7.5 Hz), 4.02 (d, 1H, J = 5.0 Hz), 4.56 (d, 1H, J = 8.5 Hz), 5.70 (s, 1H), 6.99-7.06 (m, 3H), 7.07-7.12 (m, 2H), 7.18 (t, 1H, J = 8.5 Hz), 7.34 (d, 1H, J = 7.5 Hz), 7.43 (d, 1H, J = 8.0 Hz), 7.46 (br s, 1H), 7.58 (d, 1H, J = 8.0 Hz), 8.03 (br s, 1H). 13C-NMR (CDCl3) δ: 24.2, 29.0, 29.2, 33.6, 37.7, 38.4, 41.1, 60.9, 111.4, 111.8, 118.4, 118.5, 119.4, 119.6, 120.5, 120.6, 122.1, 122.5, 123.1, 124.3, 126.9, 130.3, 136.5, 140.3, 145.3. HR-ESI-MS: Calcd for C26H27N2 [(M+H)+]: 367.2174. Found: 367.2167.

ACKNOWLEDGEMENTS
This work was supported in part by the Ministry of Education, Culture, Sports, Sciences and Technology of Japan through a Grant-in Aid for Scientific Research (No. 22590010 for M. I. and No. 23590143 for N. H.).


Reference 9

References

1. Y. C. Kong, K. F. Cheng, R. C. Cambie, and P. G. Waterman, J. Chem. Soc., Chem. Commun., 1985, 47. CrossRef
2. (a) P. C. Ng, D. D. Ho, K. H. Ng, Y. C. Kong, K. F. Cheng, and G. Stone, Eur. J. Pharmacol., 1994, 264, 1; CrossRef (b) K. F. Cheng, T. T. Wong, K. P. Chan, and Y. C. Kong, Eur. J. Med. Chem., 1992, 27, 121. CrossRef
3. (a) T. W. T. Leung, G. Cheng, C. H. Chui, S. K. W. Ho, F. Y. Lau, J. K. J. Tjong, T. C. C. Poon, J, C. O. Tang, W. C. P. Tse, K. F. Cheng, and Y. C. Kong, Chemotherapy, 2000, 46, 62; CrossRef (b) D. C. C. Wang, W. P. Fong, S. S. T. Lee, Y. C. Kong, K. F. Cheng, and G. Stone, Eur. J. Pharmacol., 1998, 362, 87. CrossRef
4. (a) H. Naka, Y. Akagi, K. Yamada, T. Imahori, T. Kasahara, and Y. Kondo, Eur. J. Org. Chem., 2007, 4635; CrossRef (b) J. Bergman and L. Venemalm, Pure & Appl. Chem., 1994, 66, 2331; CrossRef (c) K. J. Henry, Jr. and P. A. Grieco, J. Chem. Soc., Chem. Commun., 1993, 510; CrossRef (d) J. Bergman and L. Venemalm, Tetrahedron, 1992, 48, 759; CrossRef (e) J. P. Kutney, F. J. Lopez, S. P. Huang, H. Kurobe, R. Flogaus, K. Piotrowska, and S. J. Rettig, Can. J. Chem., 1991, 69, 949; CrossRef (f) J. P. Kutney, F. J. Lopez, S. P. Huang, and H. Kurobe, Heterocycles, 1989, 28, 565; CrossRef (g) J. Bergman and L. Venemalm, Tetrahedron Lett., 1988, 29, 2993. CrossRef
5. (a) M. Ishikura, K. Imaizumi, and N. Katagiri, Heterocycles, 2000, 53, 553; CrossRef (b) M. Ishikura, K. Imaizumi, and N. Katagiri, Heterocycles, 2000, 53, 2201. CrossRef
6. T. Kinoshita, S. Tatara, F. C. Ho, and U. Sankawa, Phytochemistry, 1989, 28, 147. CrossRef
7. (a) J. H. Sheu, Y. K. Cheng, H. F. Chung, P. J. Sung, and S. F. Lin, Heterocycles, 1996, 43, 1751; CrossRef (b) J. H. Sheu, Y. K. Chen, and Y. L. V. Hong, J. Org. Chem., 1993, 58, 5784; CrossRef (c) J. H. Sheu, Y. K. Chen, and Y. L. V. Hong, Tetrahedron Lett., 1991, 32, 1045; CrossRef (d) J. H. Sheu, Y. K. Chen, H. F. Chung, S. F. Lin, and P. J. Sung, J. Chem. Soc., Perkin Trans. 1, 1998, 1959; CrossRef (e) K. F. Cheng, Y. C. Kong, and T. Y. Chan, J. Chem. Soc., Chem. Commun., 1985, 48. CrossRef
8. (a) M. Ishikura, H. Komatsu, K. Yamada, T. Abe, and R. Yanada, Heterocycles, 2007, 71, 2325; CrossRef (b) M. Ishikura, R. Uemura, K. Yamada, and R. Yanada, Heterocycles, 2006, 68, 2349. CrossRef
9. There has been a report that indole-substituted methylbutenylindole was used for the dimerization: J. H. Sheu, C. A. Chen, and B. H. Chen, Chem. Commun., 1999, 203. CrossRef
10. Imine 5 (derived from 3-methylcrotonaldehyde and benzylamine) was distilled under reduced pressure; see G. D. Joly and E. N. Jacobsen, J. Am. Chem. Soc., 2004, 126, 4102. CrossRef
11. The reaction mechanism of the cleavage of the OMe group was supposed as follows: