HETEROCYCLES

Paper | Special issue | Vol. 90, No. 2, 2015, pp. 1038-1071
Received, 1st July, 2014, Accepted, 28th August, 2014, Published online, 3rd September, 2014.
DOI: 10.3987/COM-14-S(K)74

■ Simple Synthetic Method for 1-Hydroxyindole and Its Application to 1-Hydroxytryptophan Derivatives

Toshiya Kawasaki, Mutsuko Tabata, Kyoko Nakagawa, Kensuke Kobayashi, Atsushi Kodama, Tetsuya Kobayashi, Masakazu Hasegawa, Keiko Tanii, and Masanori Somei*

Noto Marine Laboratory, Institute of Nature and Environmental Technology, Faculty of Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa University, 56-7 Matsuhidai, Matsudo-shi, Chiba 270-2214, Japan

Abstract

Simple and general synthetic method for 1-hydroxy- and 1-methoxyindole is reported. Its application to the synthesis of various types of 1-hydroxy- and 1-methoxyindole derivatives is successful, especially for the synthesis of 1-hydroxytryptophan derivatives.

INTRODUCTION
We have 1-hydroxyindole hypotheses3 in which we imagine the existence of 1-hydroxy- (A, Figure 1) and/or 1-hydroperoxytryptophan (B) derivatives as a peptide component in living organisms and they could undergo nucleophilic substitution reactions3 on indole nucleus with 1-hydroxy moiety (or its phosphate ester, etc.) as a leaving group culminating in the formation of various kinds of indole natural products, such as serotonin,4 melatonin,4 bufotenin,4 pyrrolo[2,3-b]indole skeleton,5 leptosin A–C mother

skeletons,6 etc.3 In order to determine whether our hypotheses is imaginary story or not, we had to create a synthetic method for 1-hydroxyindoles, especially the one suitable for imaginary 1-hydroxytryptophan derivatives.

When the present study started, two methods were reported for the synthesis of 1-methoxyindole (1, Scheme 1). In 1974, Acheson and co-workers7 succeeded in the first preparation of 1 via unstable 1-hydroxyindole (2), starting from 2-nitroaniline (3). Using this sequence of reactions, they produced some 1-hydroxyindole derivatives,7 stabilized by electron withdrawing group at the 3-position, but Acheson’s method is not applicable for our target, 1-hydroxytryptophan derivatives. In 1981, we discovered the second method8 reacting 2-nitrotoluene (4) with N,N-dimethylformamide dimethyl acetal (DMFDMA), followed by reduction of the intermediate nitroenamine (5) with either titanium chloride or zinc and ammonium chloride. Employing the method, preparation of various 1-hydroxyindoles,3,8 1-methoxypimprinine,9 1-methoxyindole-3-acetonitrile,9 (dl)-paniculidine B,10 and (dl)-1-methoxy-6,7- secoagroclavine11 were achieved. However, use of an expensive DMFDMA and anhydrous reaction conditions are cumbersome problems to be improved. Furthermore, it is not applicable for the preparation of 1-hydroxytryptophan derivatives.
As the third one,12 we have finally discovered an oxidation method of 2,3-dihydroindole (6, Table 1) in MeOH–H2O with 30% aqueous hydrogen peroxide (30% H2O2) or urea·H2O2 addition compound in the presence of a catalytic amount of metal oxides, such as sodium tungstate,13 sodium phosphotungstate, and sodium molybdate.
This simple method12 meets our end and is suitable for the syntheses of various types of 1-hydroxyindoles as well as 1-hydroxytryptophan derivatives. This report is a full paper for the previous communications12,14 in addition to new results.

RESULTS AND DISCUSSION
I. Simple and mild synthetic method for 1-hydroxyindole (metal oxide–H2O2 method)
Since the direct oxidation of indole gave tar or polymer under various reaction conditions, we next extensively examined oxidation conditions of 2,3-dihydroindole (6) with 30% H2O2 and metal oxides.12 The formation of 1-hydroxyindole (2) in the reaction mixture was clearly deduced by thin layer monitoring. We know that 2 is quite unstable, but once 2 is converted to 1-methoxyindole (1), its stability increases to the extent which makes isolation possible,3 enough to store for six years without any detectable

decomposition under protection of light. Therefore, after oxidation of 6 at room temperature for 30 min with 30% H2O2 in the presence of metal oxides, we tried to isolate 1 by adding an excess amount of ethereal diazomethane to the reaction mixture. The results obtained under typical reaction conditions are summarized in Table 1.
As a result, we have found that sodium tungstate (Entries 1–9) and sodium phosphotungstate (Entries 10–12) are superior oxidizing catalyst to sodium molybdate and oxone. Comparing the results of Entries 1–3, 4–6, and 7–9, the employment of 0.2 mol eq. of sodium tungstate is found to be superior to 0.1 and 1.0 mol eq. Comparisons of Entries 1–3 and/or 4–6 recommend the use of 10 mol eq. of 30% H2O2. Urea·H2O2 addition compound can be used instead of 30% H2O2 to give 1 in 54% yield (Entry 13).
For the preparation of 1, m-chloroperbenzoic acid was also applicable in acetone or CH2Cl2 (Entries 14, 15). Since it is powerful oxidizing agent, reaction was performed at 0 °C for 5 min. So the control of the reaction is more difficult than the metal oxide–H2O2 method.
Thus, we could establish a simple and mild synthetic method for 1-methoxyindole which works in the presence of H2O. Employing the method we can now obtain 1 in the range of 50–58% yield from 6 in one pot operation under the reaction conditions described in the Entries 3, 6, 12, and 13.
II. Trapping of 1-hydroxyindole with alkyl, alkenyl, acyl, silyl halides, etc.
As shown in Table 1,12 the presence of unstable 1-hydroxyindole (2) in the oxidation reaction mixture was confirmed by converting it into 1-methoxyindole (1) by methylation with diazomethane. Instead of diazomethane, a mixture of Me2SO4 and K2CO3 was also found to be successful to obtain 1 in good yield.

We next tried to trap 2 as various 1-alkoxyindoles.14c Thus, the addition of allyl bromide and K2CO3 into the oxidation reaction mixture at room temperature for 1.5 h afforded 1-allyloxyindole (7a, Figure 2) in 44% yield. Under similar reaction conditions, when benzoyl chloride, t-butyldimethylsilyl chloride, and methallyl chloride were employed, 1-benzoyloxy- (7b), 1-t-butyldimethylsilyloxyindole (7c), and 1-methallyloxyindole (7d) were provided in 49, 47, and 6% yields, respectively. In the reaction with benzyl bromide, 1-benzyloxyindole (7e) and 3-benzyl-1-benzyloxyindole (8a) were isolated in 47 and 5% yields, respectively. Similarly, the reaction with prenyl bromide and cinnamyl bromide provided 1-prenyloxy- (7f), 3-prenyl-1-prenyloxyindole (8b), 1-cinnamyloxy- (7g) and 3-cinnamyl-1-cinnamyloxyindole (8c), in 7, 4, 51, and 22% yields, respectively. In the reaction with tosyl chloride, 3-tosyloxyindole (9) was obtained in 10% yield, showing that 9 is the [3,3] sigmatropic rearranged product of initially formed 1-tosyloxyindole (10).
Benzene solution containing unstable 2 was obtained after extraction of the oxidation reaction mixture with benzene. Treating the benzene solution with methoxymethyl chloride (MOMCl), 2-methoxyethoxymethoxy chloride (MEMCl), and prenyl bromide in the presence of K2CO3 and phase transfer catalyst ((n-Bu)4NHSO4) afforded 1-methoxymethoxy- (7h), 1-[2-(methoxy)ethoxy]methoxyindole (7i), and 1-prenyloxyindole (7f) in 39, 11, and 18% yields, respectively.
Generation of pure 2 in THF can be realized by the treatment of 1-t-butyldimethylsilyloxyindole (7c) with (n-Bu)4NF. Thus, the THF solution was reacted with MEMCl, MOMCl, and prenyl bromide in the presence of [(n-Bu)4NHSO4] and KOt-Bu to give 7h, 7i, and 7f in 98, 98, and 100% yields, respectively.
III. Syntheses of various 1-hydroxy- and 1-methoxyindole derivatives
Application of the metal oxide–H2O2 method to various types of 2,3-dihydroindoles was examined. Thus, using sodium tungstate under the reaction conditions described in the Entry 6 (Table 1) without methylation, 1-hydroxy-6-nitro- (12a, Scheme 2), 1-hydroxy-5-nitro- (12b), and 1-hydroxy-2-phenylindoles (12d) were prepared12 from the corresponding 2,3-dihydroindoles (11a,b,d) in 79, 26, and 56% yields, respectively. When CH2N2 is added to the reaction mixture obtained from the corresponding 2,3-dihydroindoles (11a-d), 1-methoxy-6-nitro- (13a), 1-methoxy-5-nitro- (13b), 1-methoxy-7-iodo (13c), and 1-methoxy-2-phenylindole15 (13d) were prepared12 in 60, 49, 26, and 67% yields, respectively. 1-Hydroxy-2-phenylindole (12d) was identical with the authentic sample prepared from benzoin oxime.16 It is interesting to note that considerable oxidative decarboxylation was observed in the case of 2,3-dihydroindole-2-carboxylic acid (11e), resulting in the formation of 1 and the desired methyl 1-methoxyindole-2-carboxylate (13f) in 22% and 18% yields, respectively.

The metal oxide–H2O2 method was successfully applied to indole-3-methanamine derivatives17 (Scheme 3). Employing Na2WO4·2H2O and 30% H2O2, 3-trifluoroacetylaminomethyl-1-hydroxyindole (16a) was prepared in 71% yield from the corresponding 2,3-dihydroindole (15).

When CH2N2 was added to the reaction mixture without isolation of 16a, 77% yield of 1-methoxy-3-trifluoroacetylaminomethylindole (17a) was obtained from 15. Similarly, 3-acetylaminomethyl-1-hydroxyindole (16b) was prepared in 66% yield from 14. Subsequent treatment of 16b with CH2N2 provided 85% yield of 3-acetylaminomethyl-1-methoxyindole (17b).
Similarly, 1-hydroxy-3-tosylaminomethylindole (20) was obtained in 68% yield from the corresponding 2,3-dihydroindole (19), which was derived from 3-tosylaminoindole (18) in 71% yield. Methylation of 20 with CH2N2 provided 96% yield of 1-methoxy-3-tosylaminomethylindole (21).
On the other hand, N-(2,3-dihydroindol-3-yl)methylsuccinimide (23, Scheme 4) and methyl N-(2,3-dihydroindol-3-yl)methylsuccinamate (24) are prepared by the reduction of methyl N-(indol-3-yl)-methylsuccinamate (22) with NaBH3CN in 15 and 82% yields, respectively. The metal oxide–H2O2 method worked well in the case of 24 to give the desired 1-hydroxyindole derivative (25a) in 63% yield. Subsequent methylation with CH2N2 provided the corresponding 1-methoxyindole (25b) in 95% yield.

In the cases of indoles having sulfur atom in the molecule, the metal oxide–H2O2 method was also successful to give the desired 1-hydroxyindoles (Scheme 5). First, such starting materials as 3-methylthiomethylindole (27) and 3-acetylthiomethylindole (33) were prepared from gramine (26).

Namely, initial formation of quaternary ammonium salt, followed by the nucleophilic substitution reaction with NaSMe and KSCOMe afforded 27 and 33 in 80 and 79% yields, respectively. Reduction of 27 and 33 with NaBH3CN afforded 55 and 67% respective yields of the corresponding 2,3-dihydroindoles, 28 and 34. Subsequent oxidation of 28 with Na2WO4·2H2O and 30% H2O2 for 20 min, followed by methylation with CH2N2 provided 1-methoxy-3-methylsulfinylmethyl- (30) and 1-methoxy-3-methylsulfonylmethylindole (31) in 10 and 37% yields, respectively. When the reaction time was shortened to 5 min, over oxidation was decreased and the yield of 30 increased to 27% together with 16% yield of 31. Under similar reaction conditions, omitting methylation, 1-hydroxy-3-methylsulfinylmethylindole (29) was isolated in 27% yield, while the formation of 1-hydroxy-3-methylsulfonylmethylindole (32) was not detected. Oxidation of 34 with Na2WO4·2H2O and 30% H2O2, followed by methylation with CH2N2 provided 15% yield of 3-acetylthiomethyl-1-methoxyindole (35).

The metal oxide–H2O2 method worked also well in the cases of 2,3-dihydro-N,N-dimethylindole-3-acetamide (37a, Scheme 6) and 2,3-dihydro-N,N-Dimethylindole-3-propionamide (37b). Both compounds were prepared by the corresponding indoles, 36a and 36b, in 97 and 98% yields, respectively, by the reduction with NaBH3CN in AcOH. Employing Na2WO4·2H2O and 30% H2O2, 37a and 37b provided N,N-dimethyl-1-hydroxyindole-3-acetamide (38a) and N,N-Dimethyl-1-hydroxyindole-3-propionamide (38b) in 74 and 66% yields, respectively.

Similarly, oxidation of 4a,9a-cis-1,2,3,4,4a,9a-hexahydrocarbazole (39, Scheme 7) afforded 9-hydroxy-1,2,3,4-tetrahydrocarbazole (40) in 65% yield. Subsequent methylation with CH2N2 provided 70% yield of 9-methoxy-1,2,3,4-tetrahydrocarbazole (41), which was also prepared directly from 39 in 55% yield. Oxidation of 41 with dichlorodicyanobenzoquinone in benzene afforded 9-methoxycarbazole (42) in 65% yield.
Compounds having benz[cd]indole skeletons2b were also suitable substrates for the metal oxide–H2O2 method (Scheme 8). Thus, reduction of 4-nitro-1,3,4,5-tetrahydrobenz[cd]indole (43) with NaBH3CN in AcOH–CF3CO2H provided 4-nitro-1,2,2a,3,4,5-hexahydrobenz[cd]indole (44) in 95% yield as a diastereoisomer’s mixture. This mixture was subjected to the oxidation with Na2WO4·2H2O and urea·H2O2 to afford 1-hydroxy-4-nitro-1,3,4,5-tetrahydrobenz[cd]indole (45) in 52% yield. Subsequent methylation with CH2N2 provided 1-methoxy-4-nitro-1,3,4,5-tetrahydrobenz[cd]indole (46) in 64% yield. Similar reduction of 4-(N-phenylacetylamino)-1,3,4,5-tetrahydrobenz[cd]indole (47) with NaBH3CN in

AcOH–CF3CO2H gave a mixture of diastereoisomers, 4-(N-phenylacetylamino)-1,2,2aβ,3,4β,5- (48a) and 4-(N-phenylacetylamino)-1,2,2aα,3,4β,5-hexahydrobenz[cd]indole (48b) in 47 and 41% yields, respectively. The C(4) proton of the isomer (48a) resonates at δ 4.42 with half height coupling constant of 12.5 Hz, while that of 48b at δ 4.20 with half height coupling constant of 33.5 Hz (Figure 3), suggesting that C3-, C4-, and C5-protons are all quasi-axial conformations. These data suggest both isomers have the assigned stereochemistry. Under the same oxidation conditions as 44 and after methylation with K2CO3 and Me2SO4, the mixture of 48a and 48b produced 1-methoxy-4-(N-phenylacetylamino)-1,3,4,5- tetrahydrobenz[cd]indole (49) in 40% yield.
A mixture of diastereoisomers, 4-N,N-di(n-propylamino)-1,2,2a,3,4,5-hexahydrobenz[cd]indole (51), prepared in 87% yield from 4-N,N-di(n-propylamino)-1,3,4,5-tetrahydrobenz[cd]indole (50) by the reduction with NaBH3CN in AcOH–CF3CO2H, provided 4-N,N-di(n-propylamino)-1-methoxy-1,3,4,5-tetrahydrobenz[cd]indole (52) in 46% yield after oxidation with urea·H2O2 and Na2WO4·2H2O, followed by methylation with CH2N2.
IV. Application to tryptamine derivatives
Before application of the metal oxide–H2O2 method to tryptophan derivatives, we examined tryptamine derivatives (Scheme 9). Thus Nb-acetyl-2,3-dihydrotryptamine (53a) produced Nb-acetyl-1-hydroxytryptamine (54a) in 55% yield. Similarly, Nb-methoxycarbonyl- (53b) and Nb-trifluoroacetyl-2,3-dihydrotryptamine (53c) afforded 1-hydroxy-Nb-methoxycarbonyl- (54b) and 1-hydroxy-Nb-trifluoroacetyltryptamine (54c) in 67 and 72% yields, respectively. Methylation of 54a, 54b, and 54c with CH2N2 afforded 55a, 55b, and 55c in 85, 83, and 78% yields, respectively.

When the Nb-substituent has alkyl group, the metal oxide–H2O2 method was also effective. Thus, Nb,Nb-dimethyl-2,3-dihydrotryptamine (53d) afforded 55% yield of 54d. After oxidation and methylation, the expected 55d and Nb,Nb-dimethyl-1-methoxytryptamine-N-oxide (56) were formed in 26 and 31% yields, respectively. Compound 55d is a natural product, lespedamine.7b,18 In the case of Nb-n-propylamino-2,3-dihydrotryptamine (53e), after oxidation and methylation, 1-methoxy-Nb- n-propyltryptamine (55e) and 1-methoxy-Nb-methyl-Nb-n-propyltryptamine (57) were obtained in 49 and 9% yields, respectively. It should be mentioned that we have often encountered such type of N-methylation in the reaction of 1-hydroxyindolylamines with CH2N2.
Reduction of melatonin (58) with Et3SiH in CF3CO2H gave 2,3-dihydromelatonin (59) in 83% yield. The metal oxide–H2O2 method worked well on melatonin skeleton (59) to give 1-hydroxymelatonin (60a) in 58% yield. Further methylation with CH2N2 provided 1-methoxymelatonin (60b) in 75% yield.
V. Syntheses of methyl Nb-acetyl-1-hydroxytryptophan methyl ester and related compounds
Based on the success of preparing 1-hydroxyindoles from simple structures to relatively complex molecules, application of the metal oxide–H2O2 method to (dl)-2-acetoamino-3-(2,3-dihydroindol-3- yl)propanol ((dl)-61) was examined,14b employing Na2WO4·2H2O and 30% H2O2, to provide (dl)-2-acetoamino-3-(1-hydroxyindol-3-yl)propanol ((dl)-62) in 30% yield (Scheme 10). After methylation of (dl)-62 with CH2N2 77% yield of (dl)-2-acetoamino-3-(1-methoxyindol-3-yl)propanol ((dl)-63) was obtained.
Encouraged with this success, we examined the synthesis of 1-hydroxytryptophan derivative.14b The metal oxide–H2O2 method can give birth to thus far imagined (dl)- ((dl)-65) and (S)-(+)-Nb-acetyl-1-hydroxytryptophan methyl ester ((S)-(+)-65) in 73 and 53% yields, respectively, from the corresponding 2,3-dihydroindoles, (dl)-64 and (S)-(+)-64. Methylation of (S)-(+)-65 and (dl)-65 with CH2N2 afforded (S)-(+)-Nb-acetyl-1-methoxytryptophan methyl ester ((S)-(+)-66) and (dl)-66 in 78 and 83% yields, respectively.

Contrary to our expectation, (dl)-65 and (S)-(+)-65 are stable crystalline compounds enough to X-ray crystallographic analysis. Figure 4 is an ORTEP drawing of (dl)-65. It should be stressed that 1-hydroxy group is deviated from the indole plane by 15.2°.3a-c,19 This is the reason why 1-hydroxytryptophan derivatives undergo nucleophilic substitution.3a

We have found that Nb-acyl-1-hydroxytryptamines are novel and structurally simple α2-blocker20 for the treatment of erectile dysfunction. Furthermore they have potent inhibitory activities on platelet aggregation.21 Daikon and wasabi phytoalexins are weak fungicidal alkaloids22 having stabilized 1-methoxyindole structure. Quite recently, we found that 1-hydroxy-Nb-nonanoyltryptamine had potent hair growth action.23 Judging from these facts: we hope that the chemistry of 1-hydroxyindole is a treasure field where a lot of new biologically active compounds are buried under the ground to be dug up.

EXPERIMENTAL
Melting points were determined on a Yanagimoto micro melting point apparatus and are uncorrected. Infrared (IR) spectra were determined with a Shimadzu IR-420 spectrophotometer, and proton nuclear magnetic resonance (1H-NMR) spectra with a JEOL JNM-GSX 500 or FX100S spectrometer with tetramethylsilane as an internal standard. Mass spectra (MS) were recorded on a Hitachi M-80 or JEOL SX-102A spectrometer. Preparative thin-layer chromatography (p-TLC) was performed on Merck Kiesel-gel GF254 (Type 60) (SiO2) or Merck Aluminum Oxide GF254 (Type 60/E) (Al2O3). Column chromatography was performed on silica gel (SiO2, 100-200 mesh, from Kanto Chemical Co. Inc.) or activated alumina (Al2O3, 300 meshes, from Wako Pure Chemical Industries, Ltd.) throughout the present study.
1-Methoxyindole (1) from 2,3-dihydroindole (6) — General method A: A solution of Na2WO4·2H2O (2.834 g, 8.42 mmol) in H2O (40.0 mL) was added to a solution of 6 (5.015 g, 42.1 mmol) in MeOH (375 mL). 30% H2O2 (47.657 g, 421 mmol) was added to the resultant solution at 0 °C with stirring. After stirring for 15 min at rt (16 °C), K2CO3 (20.456 g, 147 mmol) and a solution of Me2SO4 (7.972 g, 631 mmol) in MeOH (25.0 mL) were added to the reaction mixture. After stirring for 90 min at rt (16 °C), brine (330 mL) was added and the whole was extracted with CHCl3 (200 mL x 3). The extract was washed with brine, dried over Na2SO4, and evaporated under reduced pressure to leave a black oil, which was column-chromatographed on SiO2 with CHCl3–hexane (1:4, v/v) to give 1 (3.361 g, 54%). 7,8,12,14
General method B (Table 1, Entry 3): A solution of Na2WO4·2H2O (13.2 mg, 0.04 mmol) in H2O (0.5 mL) was added to a solution of 6 (47.5 mg, 0.39 mmol) in MeOH (4.0 mL). 30% H2O2 (452.5 mg, 4.0 mmol) was added to the resultant solution at 0 °C with stirring. After stirring for 30 min at rt (17 °C), ethereal CH2N2 (excess) was added to the reaction mixture with stirring at rt until the starting material was not detected on tlc monitoring. Brine was added and the whole was extracted with CH2Cl2. The extract was washed with brine, dried over Na2SO4, and evaporated under reduced pressure to leave oil, which was purified by p-TLC on SiO2 with CH2Cl2–hexane (7:3, v/v) as a developing solvent. Extraction of a band having an Rf value of 0.92–0.79 with CH2Cl2 afforded 1 (29.6 mg, 50%). Entry 6: In the same procedure for Entry 3, Na2WO4·2H2O (27.0 mg, 0.08 mmol), 6 (48.8 mg, 0.41 mmol), 30% H2O2 (464.9 mg, 4.10 mmol) were used. And the same work-up as Entry 3 afforded 1 (31.1 mg, 52%). Entry 12: In the same procedure for Entry 3, 2Na2O·P2O5·12WO4·18H2O (23.8 mg, 0.007 mmol), 6 (50.3 mg, 0.42 mmol), 30% H2O2 (479.2 mg, 4.22 mmol) were used. And the same work-up as Entry 3 afforded 1 (35.9 mg, 58%).
General method C (Table 1, Entry 13): A solution of Na2WO4·2H2O (591.4 mg, 1.79 mmol) in H2O (10.0 mL) and urea·H2O2 compound (8.437 g, 89.64 mmol) were added to a solution of 6 (1.068 g, 8.96 mmol) in MeOH (100.0 mL) at 0 °C with stirring. After stirring at rt for 15 min, K2CO3 (22.300 g, 161.3 mmol) and then a solution of Me2SO4 (3.391 g, 26.9 mmol) in MeOH (10.0 mL) were added to the reaction mixture. After the same work-up as Entry 3, 1 (717.5 mg, 54%) was obtained. Entry 14: m-Chloroperbenzoic acid (231.6 mg, 0.94 mmol), (n-Bu)4NHSO4 (7.1 mg, 0.02 mmol) and sat. aq. NaHCO3 (5.0 mL) were added to a solution of 6 (111.4 mg, 0.94 mmol) in acetone–CH2Cl2 (1:1, v/v, 5.0 mL) at 0 °C with stirring. After stirring for 5 min, brine was added. The whole was extracted with CH2Cl2 and ethereal CH2N2 (excess) was added to the extract. After stirring for 3 min, the solvent was evaporated under reduced pressure to leave oil, which was purified by column-chromatography on SiO2 to afford 1 (47.5 mg, 35%). Entry 15: In the same procedure as Entry 14, solvent was changed to CH2Cl2 (5.0 mL) only, where m-chloroperbenzoic acid (223.2 mg, 0.90 mmol), (n-Bu)4NHSO4 (7.2 mg, 0.02 mmol), 6 (107.0 mg, 0.90 mmol), and sat. aq. NaHCO3 (5.0 mL) were used. After usual work-up, 1 (52.9 mg, 40%) was obtained.
1-Allyloxyindole (7a) from 6 — Prepared according to the general method B, where Na2WO4·2H2O (611.6 mg, 1.85 mmol) in H2O (10.0 mL) was added to a solution of 6 (1.108 g, 9.29 mmol) in MeOH (20.0 mL). 30% H2O2 (10.561 g, 101.2 mmol) in MeOH (20.0 mL) was added to the resultant solution at 0 °C with stirring. After stirring for 15 min at rt (20 °C), K2CO3 (3.86 g, 27.8 mmol) and allyl bromide (3.313 g, 27.4 mmol) were added and stirred at rt for 1.5 h. Brine was added and the whole was extracted with CH2Cl2. The extract was washed with brine, dried over Na2SO4, and evaporated under reduced pressure to leave oil, which was purified by column-chromatography on SiO2 with CH2Cl2–hexane (1:9, v/v) to give 7a (711.3 mg, 44%). 7a: colorless oil. IR (film): 3050, 1449, 1220, 740 cm-1. 1H-NMR (CDCl3) δ: 4.67 (2H, dt, J=6.6, 1.2 Hz), 5.21 (1H, m), 5.35 (1H, d, J=3.4 Hz), 5.86–6.25 (1H, m), 6.30 (1H, dd, J=3.5, 1.0 Hz), 6.94–7.61 (5H, m). High resolution MS m/z: Calcd for C11H11NO: 173.0782. Found: 173.0811.
Benzoyloxyindole (7b) from 6 — Prepared according to the general method B, where Na2WO4·2H2O (57.1 mg, 0.17 mmol) in H2O (1.0 mL), 6 (103.0 mg, 0.86 mmol) in MeOH (8.0 mL), and 30% H2O2 (981.2 mg, 8.66 mmol) in MeOH (2.0 mL) were used. The reaction mixture was extracted with benzene and benzene layer was dried over Na2SO4. After filtering off Na2SO4, K2CO3 (583.3 mg, 3.89 mmol) and benzoyl chloride (483.2 mg, 2.59 mmol) were added to the benzene solution and stirred at rt for 1.5 h. H2O was added and the whole was extracted with CH2Cl2. The extract was washed with brine, dried over Na2SO4, and evaporated under reduced pressure to leave oil, which was purified by column-chromatography on SiO2 with CH2Cl2–hexane (3:7, v/v) to give 7b (100.8 mg, 49%). 7b: mp 55.5–56.0 °C (lit.19b mp 49–50 °C, pale brown needles, recrystallized from MeOH). IR (KBr): 1767, 1600, 1446, 1323, 1236, 1184, 1075, 1039, 1012, 1002, 754, 729, 700 cm-1. UV λmaxMeOH nm (log ε): 217 (4.50), 265 (3.94), 293 (3.60). 1H-NMR (CDCl3) δ: 6.53 (1H, d, J=3.7 Hz), 6.96–7.35 (4H, m), 7.35–7.82 (4H, m), 8.21 (2H, dd, J=8.2, 1.7 Hz). MS m/z: 237 (M+). Anal. Calcd for C15H11NO2: C, 75.94; H, 4.67; N, 5.90. Found: C, 75.85; H, 4.62; N, 5.84.
1-t-Butyldimethylsilyloxyindole (7c) from 6 — Prepared according to the general method B, where Na2WO4·2H2O (75.9 mg, 0.23 mmol) in H2O (1.3 mL), 6 (136.9 mg, 1.15 mmol) in MeOH (10.0 mL), and 30% H2O2 (1.304 g, 11.5 mmol) in MeOH (3.0 mL) were used. Silylation was carried out according to the method for 7b with K2CO3 (715.5 mg, 5.18 mmol) and t-butyldimethylsilyl chloride (520.2 mg, 3.45 mmol). After usual work-up and purification, 7c (133.1 mg, 47%) was obtained. 7c: colorless oil. IR (film): 1472, 1436, 1266, 1074, 1035, 836, 787, 739 cm-1. 1H-NMR (CDCl3) δ: 0.23 (6H, s), 1.10 (9H, s), 6.31 (1H, d, J=3.4 Hz), 7.01 (1H, t, J=6.6 Hz), 7.07 (1H, d, J=3.4 Hz), 7.17 (1H, t, J=6.6 Hz), 7.31 (1H, d, J=6.6 Hz), 7.53 (1H, d, J=6.6 Hz). High resolution MS m/z: Calcd for C14H21NOSi: 247.1390. Found: 247.1376.

1-Methallyloxyindole (7d) from 6 — Prepared according to the general method B, where Na2WO4·2H2O (26.7 mg, 0.08 mmol) in H2O (0.5 mL), 6 (48.0 mg, 0.40 mmol) in MeOH (4.0 mL), and 30% H2O2 (461.7 mg, 4.0 mmol) in MeOH (1.0 mL) were used. Methallylation was carried out with K2CO3 (253.3 mg, 1.80 mmol) and methallyl chloride (110.5 mg, 1.20 mmol). After usual work-up and purification, 7d (4.2 mg, 6%) was obtained. 7d: colorless oil. IR (film): 1653, 1450, 1323, 1222, 740 cm-1. 1H-NMR (CDCl3) δ: 1.97 (3H, t, J=1.2 Hz), 4.60 (2H, s), 5.03 (2H, m), 6.32 (1H, dd, J=3.4, 0.7 Hz), 7.00–7.63 (5H, m). High resolution MS m/z: Calcd for C12H13NO: 187.0972. Found: 187.0984.
1-Benzyloxyindole (7e) and 3-benzyl-1-benzyloxyindole (8a) from 6 — Prepared according to the general method B, where Na2WO4·2H2O (60.3 mg, 0.18 mmol) in H2O (1.0 mL), 6 (108.7 mg, 0.91 mmol) in MeOH (8.0 mL), and 30% H2O2 (1.036 g, 9.13 mmol) in MeOH (2.0 mL) were used. Benzylation was carried out with K2CO3 (568.1 mg, 4.11 mmol) and benzyl bromide (483.2 mg, 2.74 mmol). After usual work-up and purification, 7e (96.0 mg, 47%) and 8a (14.7 mg, 5%) were obtained. 7e: colorless oil. IR (film): 1455, 1323, 1221, 1074, 1032, 756, 740, 697 cm-1. 1H-NMR (CDCl3) δ: 5.15 (2H, s), 6.23 (1H, d, J=3.4 Hz), 6.98 (1H, d, J=3.4 Hz), 6.98–7.22 (2H, m), 7.22–7.44 (6H, m), 7.44–7.60 (1H, m). High resolution MS m/z: Calcd for C15H13NO: 223.0996. Found: 223.0992. 8a: colorless oil. IR (KBr, film): 1494, 1450, 734, 695 cm–1. 1H-NMR (CDCl3) δ: 4.00 (2H, s), 5.12 (2H, s), 6.11 (1H, s), 6.85–7.11 (14H, m). High resolution MS m/z: Calcd for C22H15NO: 313.1465. Found: 313.1468.
1-Prenyloxyindole (7f) and 3-prenyl-1-prenyloxyindole (8b) from 6 — Prepared according to the general method B, where Na2WO4·2H2O (61.9 mg, 0.19 mmol) in H2O (1.0 mL), 6 (111.2 mg, 0.93 mmol) in MeOH (8.0 mL), and 30% H2O2 (1.087 g, 10.1 mmol) in MeOH (2.0 mL) were used. Prenylation was carried out with K2CO3 (470.6 mg, 6.84 mmol) and prenyl bromide (380.2 mg, 0.51 mmol). After usual work-up and purification 7f (13.5 mg, 7%) and 8b (9.3 mg, 4%) were obtained. 7f: pale yellow oil. IR (film): 3050, 2980, 2930, 1670, 1450, 1324, 1222, 1075, 1030, 740 cm-1. 1H-NMR (CDCl3) δ: 1.48 (3H, s), 1.68 (3H, s), 4.54 (2H, d, J=7.9 Hz), 5.44 (1H, t, J=7.2 Hz), 6.21 (1H, dd, 3.6, 1.0 Hz), 6.88–7.50 (5H, m). High resolution MS m/z: Calcd for C13H15NO: 201.1153. Found: 201.1155. 8b: pale red oil. IR (film): 2980, 2920, 1666, 1612, 1447, 1375, 1088, 1008, 735 cm–1. 1H-NMR (CDCl3) δ: 1.58 (3H, s), 1.74 (3H, s), 1.76 (6H, s), 3.38 (2H, dd, J=7.0, 1.0 Hz), 4.60 (2H, d, J=7.5 Hz), 5.28–5.61 (2H, m), 6.94–7.56 (5H, m). High resolution MS m/z: Calcd for C18H23NO: 269.1753. Found: 269.1765.
1-Prenyloxyindole (7f) from 6 — Prepared according to the general method B, where Na2WO4·2H2O (65.2 mg, 0.19 mmol) in H2O (1.0 mL), 6 (116.4 mg, 0.98 mmol) in MeOH (9.0 mL), and 30% H2O2 (1.143 g, 10.0 mmol) in MeOH (1.0 mL) were used. Prenylation was carried out according to the method for 7b with NEt3 (1.4 mL, 9.8 mmol), (n-Bu)4NBr (32.3 mg, 0.10 mmol), and prenyl bromide (1.339 g, 8.71 mmol). After usual work-up and purification, 7f (35.7 mg, 18%) was obtained.
1-Prenyloxyindole (7f) from 7c — A solution of prenyl bromide (112.2 mg, 0.72 mmol) in anhydrous THF (1.0 mL), KOt-Bu (91.7 mg, 0.82 mmol), and a solution of (n-Bu)4NF·3H2O (120.6 mg, 0.34 mmol) in anhydrous THF (1.0 mL) were added to a solution of 7c (75.4 mg, 0.37 mmol) in anhydrous THF (1.0 mL) at rt. After usual work-up and purification, 7f (75.4 mg, 100%) was obtained.
1-Cinnamyloxyindole (7g) and 3-cinnamyl-1-cinnanyloxyindole (8c) from 6 — Prepared according to the general method B, where Na2WO4·2H2O (57.9 mg, 0.17 mmol) in H2O (1.0 mL). 6 (104.1 mg, 0.87 mmol) in MeOH (8.0 mL), and 30% H2O2 (991.9 mg, 8.7 mmol) in MeOH (2.0 mL) were used. Cinnamylation was carried out with K2CO3 (544.6 mg, 3.91 mmol) and cinnamyl bromide (520.8 mg, 2.61 mmol). After usual work-up and purification, 7g (110.5 mg, 51%) and 8c (80.2 mg, 22%) were obtained. 7g: pale brown oil. IR (film): 3050, 3017, 2920, 1495, 1449, 1323, 1221, 1074, 1030, 965, 757, 738, 691 cm-1. 1H-NMR (CDCl3) δ: 4.81 (2H, d, J=6.0 Hz), 6.31 (1H, dd, J=3.5, 1.0 Hz), 6.25–6.72 (2H, m), 6.96–7.60 (10H, m). High resolution MS m/z: Calcd for C17H15NO: 249.1148. Found: 249.1150. 8c: pale yellow oil. IR (film): 3050, 3017, 2920, 1496, 1449, 964, 738, 692 cm–1. 1H-NMR (CDCl3) δ: 3.58 (2H, dd, J=5.3, 1.0 Hz), 4.77 (2H, d, J=5.5 Hz), 6.13–6.72 (4H, m), 6.93–7.61 (15H, m). High resolution MS m/z: Calcd for C26H23NO: 365.1800. Found: 365.1789.
1-Methoxymethoxyindole (7h) from 6 — Prepared according to the general method C, where Na2WO4·2H2O (63.7 mg, 0.19 mmol) in H2O (1.0 mL), 6 (115.1 mg, 0.96 mmol) in MeOH (10.0 mL), and urea·H2O2 compound (927.2 mg, 9.66 mmol) were used. Methoxymethoxylation was carried out according to the method for 7b with K2CO3 (2.403 g, 17.38 mmol), (n-Bu)4NBr (31.1 mg, 0.09 mmol), and methoxymethyl chloride (233.3 mg, 2.89 mmol) in benzene (1.0 mL). After usual work-up and purification, 7h (66.0 mg, 39%) was obtained. 7h: mp 27.0–27.5 °C (colorless prisms, recrystallized from hexane). IR (KBr): 2970, 1445, 1330, 1230, 1182, 1100, 1089, 1030, 920, 740 cm-1. 1H-NMR (CDCl3) δ: 3.66 (3H, s), 5.17 (2H, s), 6.37 (1H, d, J=3.5 Hz), 7.11 (1H, t, J=7.4 Hz), 7.20–7.26 (3H, m), 7.42 (1H, d, J=8.1 Hz), 7.58 (1H, d, J=7.9 Hz). MS m/z: 177 (M+). Anal. Calcd for C10H11NO2: C, 67.78; H, 6.26; N, 7.90. Found: C, 67.64; H, 6.33; N, 7.86.
1-Methoxymethoxyindole (7h) from 7c — A solution of methoxymethyl chloride (56.2 mg, 0.69 mmol) in anhydrous THF (1.0 mL), KOt-Bu (91.2 mg, 0.81 mmol), and a solution of (n-Bu)4NF·3H2O (111.1 mg, 0.35 mmol) in anhydrous THF (1.0 mL) were added to a solution of 7c (85.4 mg, 0.34 mmol) in anhydrous THF (1.0 mL) at rt. After usual work-up and purification, 7h (59.7 mg, 98%) was obtained.
1-(2-Methoxyethoxymethoxy)indole (7i) from 6 — Prepared according to the general method B, where Na2WO4·2H2O (61.4 mg, 0.19 mmol) in H2O (1.0 mL), 6 (111.1 mg, 0.93 mmol) in MeOH (9.0 mL), and 30% H2O2 (1.073 g, 9.46 mmol) in MeOH (1.0 mL) were used. Methoxyethoxymethoxylation was carried out according to the method for 7b with NEt3 (2.6 mL, 18.6 mmol), (n-Bu)4NBr (29.9 mg, 0.09 mmol), and 2-methoxyethoxymethyl chloride (1.038 g, 8.35 mmol). After usual work-up and purification, 7i (23.2 mg, 11%) and indole (2.2 mg, 2%) were obtained. 7i: colorless oil. IR (KBr): 2920, 2890, 1450, 1320, 1220, 1105, 1030, 920, 875, 845, 760, 740 cm-1. 1H-NMR (CDCl3) δ: 3.41 (3H, s), 3.59–3.65 (2H, m), 3.93–3.99 (2H, m), 5.27 (2H, s), 6.36 (1H, dd, J=3.5, 1.0 Hz), 7.10 (1H, ddd, J=7.9, 6.9, 1.0 Hz), 7.22 (1H, ddd, J=8.3, 6.9, 1.0 Hz), 7.33 (1H, d, J=3.5 Hz), 7.42 (1H, dd, J=8.3, 1.0 Hz), 7.58 (1H, ddd, J=7.9, 1.0, 1.01 Hz). High resolution MS m/z: Calcd for C12H15NO3: 221.1050. Found: 221.1049.
1-(2-Methoxyethoxymethoxy)indole (7i) from 7c — A solution of 2-methoxyethoxymethyl chloride (98.8 mg, 0.79 mmol) in anhydrous THF (1.0 mL), KOt-Bu (97.2 mg, 0.86 mmol), and a solution of (n-Bu)4NF·3H2O (125.8 mg, 0.39 mmol) in anhydrous THF (1.0 mL) were added to a solution of 7c (94.9 mg, 0.38 mmol) in anhydrous THF (1.0 mL) at rt. After usual work-up and purification, 7i (83.3 mg, 98%) was obtained.

3-Tosyloxyindole (9) from 6 — Prepared according to the general method B, where Na2WO4·2H2O (559.6 mg, 1.69 mmol) in H2O (10.0 mL), 6 (1.009 g, 8.48 mmol) in MeOH (80.0 mL), and 30% H2O2 (9.610 g, 84.8 mmol) in MeOH (20.0 mL) were used. Tosylation was carried out with K2CO3 (5.270 g, 38.2 mmol) and tosyl chloride (4.848 g, 25.5 mmol). After usual work-up and purification, 9 (252.2 mg, 10%) was obtained. 9: mp 112–114°C (colorless prisms, recrystallized from MeOH). IR (KBr): 3390, 3120, 1595, 1453, 1370, 1190, 1175, 1090, 1063, 843, 812, 742, 723, 657, 555, 545, 503 cm-1. 1H-NMR (CDCl3) δ: 2.41 (3H, s), 6.95–7.30 (8H, m), 7.75 (2H, d, J=8.3 Hz). MS m/z: 287 (M+). Anal. Calcd for C15H13NO3S: C, 62.70; H, 4.56; N, 4.87. Found: C, 62.70; H, 4.53; N, 4.72.
1-Hydroxy-6-nitroindole (12a) from 11a — Prepared according to the general method B, where Na2WO4·2H2O (18.8 mg, 0.06 mmol), 11a (101.3 mg, 0.57 mmol) in MeOH (10.0 mL), and 30% H2O2 (0.58 mL, 5.7 mmol) were used. After usual work-up and purification, 12a (80.1 mg, 79%) was obtained. 12a: mp 153–155 °C (decomp., pale orange needles, recrystallized from CHCl3). IR (KBr): 3240, 1617, 1586, 1514, 1481, 1357, 1332, 1280, 1095, 1056, 863, 811, 751, 731 cm-1. UV λmaxMeOH nm (log ε): 264 (4.01), 321 (3.94), 361 (3.73). 1H-NMR (CDCl3–CD3OD. 95:5, v/v) δ: 6.43 (1H, d, J=3.3 Hz), 7.51 (1H, d, J=3.3 Hz), 7.61 (H, d, J=8.8 Hz), 7.95 (1H, dd, J=8.8, 2.1 Hz), 8.42 (1H, dd, J=2.1 Hz). MS m/z: 178 (M+). Anal. Calcd for C8H6N2O3: C, 53.94; H, 3.39; N, 15.72. Found: C, 54.03; H, 3.45; N, 15.73.
1-Hydroxy-5-nitroindole (12b) from 11b — Prepared according to the general method B, where Na2WO4·2H2O (81.6 mg, 0.25 mmol) in H2O (2.0 mL), 11b (202.9 mg, 1.23 mmol) in MeOH (20.0 mL), and 30% H2O2 (1.26 mL, 12.3 mmol) were used. After usual work-up and purification, 11b (52.7 mg, recovery, 26%), 5-nitroindole (9.4 mg, 5%), and 12b (91.7 mg, 42%) were obtained. The mixture of 11b and 5-nitroindoe was successfully separated by column chromatography on Al2O3 with benzene–EtOAc (10:1, v/v). 12b: mp 175–176 °C (decomp., brown needles, recrystallized from CHCl3). IR (KBr, film): 1613, 1584, 1508, 1358, 1339, 756, 720 cm-1. UV λmaxMeOH nm (log ε): 254 (4.07), 275 (4.20), 331 (3.81). 1H–NMR (CDCl3–CD3OD, 95:5, v/v) δ: 6.45 (H, d, J=3.4 Hz), 7.52 (1H, d, J=3.4 Hz), 7.60 (1H, d, J=8.9 Hz), 7.98 (1H, dd, J=8.8, 2.2 Hz), 8.38 (1H, br s). MS m/z: 178 (M+). Anal. Calcd for C8H6N2O3: C, 53.94; H, 3.39; N, 15.72. Found: C, 53.66; H, 3.37; N, 15.71.
1-Hydroxy-2-phenylindole (12d) from 2,3-dihydro-2-phenylindole (11d) — Prepared according to the general method B, where Na2WO4·2H2O (17.4 mg, 0.053 mmol), 11d (51.5 mg, 0.26 mmol) in 4.0 mL of MeOH, and 30% H2O2 (299.4 mg, 2.64 mmol) in MeOH (1.0 mL) were used. The crude product was purified by p-TLC on SiO2 with CH2Cl2–MeOH (98:2, v/v) as a developing solvent to afford 12d (30.9 mg, 56%). 12d: mp 174.0–175.0 °C (decomp., pale yellow needles, recrystallized from CHCl3, lit.,16 mp 175 °C). IR (KBr): 2400, 1625, 1370, 756, 740, 683 cm-1. 1H-NMR (10% CD3OD in CDCl3) δ: 6.52 (1H, s, C3–H, deuterated during measuring), 6.88–7.62 (7H, m), 7.68–7.92 (2H, m). MS m/z: 209 (M+). Identical with the authentic sample prepared from benzoin oxime.16
1-Methoxy-6-nitroindole (13a) from 2,3-dihydro-6-nitroindole (11a) — Prepared according to the general method B, where Na2WO4·2H2O (9.0 mg, 0.027 mmol), 11a (44.8 mg, 0.27 mmol) in MeOH (3.0 mL), and 30% H2O2 (309.7 mg, 2.73 mmol) were used. After methylation, usual work-up, and purification, 13a (31.3 mg, 60%) and 6-nitroindole (3.8 mg, 9%) were obtained. 13a: mp 90.0–91.0 °C (yellow needles, recrystallized from MeOH). IR (KBr): 1613, 1584, 1508, 1358, 1339, 756, 720 cm-1. 1H-NMR (CDCl3) δ: 4.17 (3H, s), 6.45 (1H, dd, J=3.4 and 1.0 Hz), 7.52 (1H, d, J=3.4 Hz), 7.60 (1H, d, J=8.8 Hz), 7.98 (1H, dd, J=8.8, 2.2 Hz), 8.38 (1H, br d, J=2.2 Hz). MS m/z: 192 (M+). Anal. Calcd for C9H8N2O3: C, 56.25; H, 4.20; N, 14.58. Found: C, 56.21; H, 4.17; N, 14.73.
1-Methoxy-5-nitroindole (13b) from 2,3-dihydro-5-nitroindole (11b) — Prepared according to the general method B, where Na2WO4·2H2O (16.4 mg, 0.05 mmol), 11b (40.8 mg, 0.29 mmol) in MeOH (3.0 mL), and 30% H2O2 (282.0 mg, 2.48 mmol) in MeOH (2.0 mL) were used. After methylation, usual work-up, and purification, 13b (23.2 mg, 49%), unreacted starting material (17.1 mg, 42%), and 5-nitroindole (1.1 mg, 3%) were obtained. 13b: mp 89.5–90.5 °C (yellow plates, recrystallized from MeOH). IR (KBr): 1615, 1580, 1512, 1324, 1066, 737 cm-1. 1H-NMR (CDCl3) δ: 4.14 (3H, s), 6.54 (1H, dd, J=3.6, 0.8 Hz), 7.38 (1H, d, J=3.6 Hz), 7.44 (1H, d, J=9.0 Hz), 8.12 (1H, dd, J=9.0, 2.1 Hz), 8.54 (1H, d, J=2.1 Hz). MS m/z: 192 (M+). Anal. Calcd for C9H8N2O3: C, 56.25; H, 4.20; N, 14.58. Found: C, 56.25; H, 4.17; N, 14.50.
7-Iodo-1-methoxyindole (13c) from 2,3-dihydro-7-iodoindole (11c) — Prepared according to the general method B, where Na2WO4·2H2O (14.7 mg, 0.045 mmol), 11c (218.7 mg, 0.89 mmol) in MeOH (5.0 mL), and 30% H2O2 (303.6 mg, 2.68 mmol) in MeOH (4.0 mL) were used. After usual work-up and purification, 13c (62.6 mg, 26%), 7-iodoindole (9.9 mg, 5%), and unreacted starting material (117.5 mg, 54%) were obtained. 13c: mp 35.0–35.5 °C (colorless plates, recrystallized from hexane). IR (KBr): 1544, 1333, 1276, 1033, 948, 775 cm-1. 1H-NMR (CDCl3) δ: 4.08 (3H, s), 6.31 (1H, d, J=3.4 Hz), 6.82 (1H, t, J=7.6 Hz), 7.29 (1H, d, J=3.4 Hz), 7.54 (1H, dd, J=7.6, 1.0 Hz), 7.68 (1H, dd, J=7.6, 1.0 Hz). MS m/z: 273 (M+). Anal. Calcd for C9H8INO: C, 39.59; H, 2.95; N, 5.12. Found: C, 39.53; H, 2.99; N, 5.13.
1-Methoxy-2-phenylindole (13d) — a) From 2,3-dihydro-2-phenylindole (11d); prepared according to the general method B, where Na2WO4·2H2O (17.7 mg, 0.054 mmol), 11d (52.3 mg, 0.27 mmol) in MeOH (4.0 mL), and 30% H2O2 (304.1 mg, 2.68 mmol) in MeOH (1.0 mL) were used. After usual work-up and purification, 13d (40.0 mg, 67%) and 2-phenylindole (3.9 mg, 8%) were obtained. 13d: mp 47.0–48.0 °C (lit.,15 mp 49–51 °C, pale yellow plates, recrystallized from MeOH). IR (KBr): 1597, 956, 760, 741 cm-1. 1H-NMR (CDCl3) δ: 3.73 (3H, s), 6.56 (1H, s), 7.00–7.66 (7H, m), 7.73–7.91 (2H, m). Anal. Calcd for C15H13NO: C, 80.69; H, 5.87; N, 6.27. Found: C, 80.77; H, 5.91; N, 6.04. b) From 1-hydroxy-2-phenylindole (12d): ethereal CH2N2 (excess) was added to a solution of 12d (30.9 mg, 0.15 mmol) in MeOH (3.0 mL) with stirring at rt until the starting material was not detected on tlc monitoring. The crude product was purified by p-TLC on SiO2 with EtOAc–hexane (1:4, v/v) as a developing solvent to afford 13d (28.3 mg, 86%).
Methyl 1-methoxyindole-2-carboxylate (13f) from 2,3-dihydroindole-2-carboxylic acid (11e) — Prepared according to the general method B, where Na2WO4·2H2O (20.8 mg, 0.063 mmol), 11e (51.5 mg, 0.31 mmol) in MeOH (4.0 mL), and 30% H2O2 (358.2 mg, 3.16 mmol) in MeOH (1.0 mL) were used. After usual work-up and purification, 1 (10.4 mg, 22%) and 13f (11.4 mg, 18%) were obtained. 13f: mp 40.5–41.5 °C (colorless plates, recrystallized from MeOH). IR (KBr): 1723, 1239, 1209, 1085, 738 cm-1. 1H-NMR (CDCl3) δ: 3.93 (3H, s), 4.19 (3H, s), 7.08 (1H, d, J=1.2 Hz), 7.02–7.54 (3H, m), 7.61 (1H, dt, J=7.9, 1.0 Hz). MS m/z: 205 (M+). Anal. Calcd for C11H11NO3: C, 64.38; H, 5.40; N, 6.83. Found: C, 64.19; H, 5.45; N, 7.00.
1-Hydroxy-Nb-trifluoroacetylindole-3-methanamine (16a) from 15 — Prepared according to the general method B, where Na2WO4·2H2O (148.7 mg, 0.45 mmol) in H2O (4.5 mL), 15 (551.2 mg, 2.26 mmol) in MeOH (50.0 mL), and 30% H2O2 (2.575 g, 22.6 mmol) in MeOH (5.0 mL) were used. After usual work-up, the crude product was column-chromatographed on SiO2 with EtOAc–hexane (3:1, v/v) to give 16a (414.5 mg, 71%). 16a: mp 123.5–124.5 °C (colorless needles, recrystallized from CH2Cl2). IR (KBr): 3390, 3305, 1694, 1566, 1541, 1353, 1252, 1206, 1178, 1169, 1151, 1103, 755, 747, 682 cm-1. 1H-NMR (CD3OD) δ: 4.59 (2H, s), 7.03 (1H, dd, J=8.0, 0.9 Hz), 7.17 (1H, dd, J=8.0, 0.9 Hz), 7.28 (1H, s), 7.38 (1H, ddd, J=8.0, 0.9, 0.7 Hz), 7.57 (1H, ddd, J=8.0, 0.9, 0.7 Hz). High resolution MS m/z: Calcd for C11H9F3N2O2: 258.0615. Found: 258.0617.
3-Acetylaminomethyl-1-hydroxyindole (16b) from 3-acetylaminomethyl-2,3-dihydroindole (14) — Prepared according to the method for 16a, where Na2WO4·2H2O (149.8 mg, 0.45 mmol) in H2O (4.5 mL), 14 (688.0 mg, 3.16 mmol) in MeOH (55.0 mL), and 30% H2O2 (2.574 g, 22.7 mmol) in MeOH (5.0 mL) were used. After usual work-up and purification, 16b (302.5 mg, 66%) was obtained. 16b: mp 132.5–133.0 °C (pale yellow prisms, recrystallized from CH2Cl2). IR (KBr): 3330, 2810, 1603, 1538, 1406, 1366, 1320, 1244, 1103, 1028, 1006, 743, 667, 570 cm-1. 1H-NMR (5% CD3OD–CDCl3) δ: 1.96 (3H, s), 4.49 (2H, s), 7.08 (1H, dd, J=7.7, 7.3 Hz), 7.18 (1H, s), 7.22 (1H, dd, J=8.1, 7.3 Hz), 7.45 (1H, d, J=8.1 Hz), 7.54 (1H, d, J=7.7 Hz). MS m/z: 204 (M+). Anal. Calcd for C11H12N2O2·1/8H2O: C, 63.99; H, 5.98; N, 13.57. Found: C, 64.15; H, 5.79; N, 13.60.
1-Methoxy-Nb-trifluoroacetylindole-3-methanamine (17a) from 2,3-dihydro-3-trifluoroacetylindole-3-methanamine (15) — Prepared according to the general method B, where Na2WO4·2H2O (14.8 mg, 0.04 mmol) in H2O (0.5 mL), 15 (54.1 mg, 0.22 mmol) in MeOH (6.0 mL), and 30% H2O2 (266.6 mg, 2.35 mmol) in MeOH (1.0 mL) were used. After methylation and work-up, the product was purified by column-chromatography on SiO2 with CHCl3–hexane (3:1, v/v) to give 17a (46.5 mg, 77%). 17a: mp 70.5–71.0 °C (colorless prisms, recrystallized from benzene–hexane). IR (KBr): 3290, 1715, 1695, 1561, 1208, 1180, 1159, 738, 722 cm-1. UV λmaxMeOH nm (log ε): 219 (4.57), 272 (3.73), 288 (3.72). 1H-NMR (CDCl3) δ: 4.10 (3H, s), 4.68 (2H, d, J=5.3 Hz), 6.43 (1H, br s), 7.18 (1H, t, J=7.8 Hz), 7.31 (1H, s), 7.31 (1H, t, J=7.8 Hz), 7.46 (1H, d, J=7.8 Hz), 7.57 (1H, d, J=7.8 Hz). High resolution MS m/z: Calcd for C12H11F3N2O2: 272.0772. Found: 272.0756.
1-Methoxy-Nb-acetylindole-3-methanamine (17b) from 3-acetylaminomethyl-2,3-dihydroindole (14) — Prepared according to the general method B, where Na2WO4·2H2O (22.8 mg, 0.07 mmol) in H2O (0.5 mL), 14 (64.9 mg, 0.34 mmol) in MeOH (6.0 mL), and 30% H2O2 (388.0 mg, 3.42 mmol) in MeOH (1.0 mL) were used. After methylation and work-up, the product was purified by column-chromatography on SiO2 with CHCl3–MeOH–28% aq. NH3 (100:1:0.1, v/v) to give 17b (43.6 mg, 59%). 17b: mp 132.5–133.0 °C (colorless prisms, recrystallized from benzene). IR (KBr): 3200, 3040, 1623, 1533, 1450, 1245, 735 cm-1. UV λmaxMeOH nm (log ε): 222 (4.51), 273 (3.72), 288 (3.72). 1H-NMR (CDCl3) δ: 1.98 (3H, s), 4.07 (3H, s), 4.56 (2H, d, J=5.1 Hz), 5.65 (1H, br s), 7.14 (1H, t, J=8.2 Hz), 7.24 (1H, s), 7.28 (1H, t, J=8.2 Hz), 7.43 (1H, d, J=8.2 Hz), 7.60 (1H, d, J=8.2 Hz). MS m/z: 218 (M+). Anal. Calcd for C12H14N2O2: C, 66.04; H, 6.47; N, 12.84. Found: C, 65.91; H, 6.47; N, 12.71.
3-Acetylaminomethyl-1-methoxyindole (17b) from 16b — Ethereal CH2N2 (excess) was added to a solution of 16b (11.8 mg, 0.058 mmol) in MeOH (1.0 mL) and stirring was continued at rt for 30 min. After evaporation of the solvent under reduced pressure, the residue was column-chromatographed on SiO2 with CH2Cl2–MeOH (97:3, v/v) to give 17b (10.7 mg, 85%).

2,3-Dihydro-3-tosylaminomethylindole (19) from 3-tosylaminomethylindole (18) — 95% NaBH3CN (247.7 mg, 3.74 mmol) was added to a solution of 18 (201.8 mg, 0.67 mmol) in AcOH (10.0 mL) at rt and stirring was continued for 5 h. After adding H2O under ice cooling, the solvent was evaporated under reduced pressure. The residue was made alkaline by adding H2O and 8% NaOH. The whole was extracted with CH2Cl2–MeOH (95:5, v/v). The extract was washed with brine, dried over Na2SO4, and evaporated under reduced pressure to leave a residue, which was column-chromatographed on SiO2 with CH2Cl2–MeOH (99:1, v/v) to give 18 (16.5 mg, recovery, 8%) and 19 (144.3 mg, 71%) in the order of elution. 19: colorless hard oil. IR (KBr): 3320, 3050, 2910, 1592, 1481, 1460, 1423, 1323, 1155, 1041, 755 cm-1. 1H-NMR (CD3OD) δ: 2.42 (3H, s), 2.92 (1H, dd, J=12.8, 5.3 Hz), 3.06 (1H, dd, J=12.8, 5.3 Hz), 3.27 (1H, dd, J=9.3, 5.7 Hz), 3.30–3.38 (1H, m), 3.51 (1H, dd, J=9.3, 8.6 Hz), 6.63 (1H, d, J=7.9 Hz), 6.65 (1H, td, J=7.3, 0.9 Hz), 6.98 (1H, t, J=7.9 Hz), 7.03 (1H, d, J=7.3 Hz), 7.37 (2H, m), 7.72 (2H, m). MS m/z: 302 (M+). Anal. Calcd for C16H18N2O2S: C, 63.55; H, 6.00; N, 9.26. Found: C, 63.45; H, 6.04; N, 9.16.
1-Hydroxy-3-tosylaminomethylindole (20) from 19 — Prepared according to the general method B, where Na2WO4·2H2O (60.6 mg, 0.18 mmol) in H2O (1.8 mL), 19 (277.4 mg, 0.92 mmol) in MeOH (13.0 mL), and 30% H2O2 (1.049 g, 9.26 mmol) in MeOH (5.0 mL) were used. After usual work-up, 20 (197.5 mg, 68%) was obtained. 20: mp 134.0–135.5 °C (colorless needles, recrystallized from CHCl3). IR (KBr): 3390, 3320, 1396, 1318, 1303, 1230, 1157, 1097, 1020, 817, 732 cm-1. 1H-NMR (CD3OD) δ: 2.39 (3H, s), 4.18 (2H, s), 6.94 (1H, ddd, J=8.0, 7.0, 1.0 Hz), 7.08 (1H, s), 7.11 (1H, ddd, J=8.0, 7.0, 1.0 Hz), 7.28 (2H, m), 7.29 (1H, dt, J=8.0, 1.0 Hz), 7.39 (1H, dt, J=8.0, 1.0 Hz), 7.68 (2H, m). MS m/z: 316 (M+). Anal. Calcd for C16H16N2O3S·1/4H2O: C, 59.89; H, 5.18; N, 8.73. Found: C, 59.91; H, 5.00; N, 8.71.
1-Methoxy-3-tosylaminomethylindole (21) from 20 — Ethereal CH2N2 (excess) was added to a solution of 20 (32.3 mg, 0.10 mmol) in MeOH (1.0 mL) and stirring was continued at rt for 30 min. After evaporation of the solvent under reduced pressure, the residue was column-chromatographed on SiO2 with CH2Cl2 to give 21 (32.2 mg, 96%). 21: mp 176.0–178.5 °C (colorless prisms, recrystallized from MeOH). IR (KBr): 3300, 1600, 1423, 1315, 1243, 1145, 1089, 1024, 952, 866, 812, 746, 681, 541 cm-1. 1H-NMR (5% CD3OD–CDCl3) δ: 2.43 (3H, s), 4.02 (3H, s), 4.25 (2H, s), 7.07 (1H, ddd, J=8.0, 7.1, 1.0 Hz), 7.10 (1H, s), 7.23 (1H, ddd, J=8.2, 7.1, 1.0 Hz), 7.28 (2H, m), 7.37 (1H, dt, J=8.2, 1.0 Hz), 7.41 (1H, dt, J=8.0, 1.0 Hz), 7.74 (2H, m). MS m/z: 330 (M+). Anal. Calcd for C17H18N2O3S: C, 61.80; H, 5.49; N, 8.48. Found: C, 61.71; H, 5.50; N, 8.41.
Methyl N-(2,3-dihydroindol-3-yl)methylsuccinamate (24) and N-(2,3-Dihydroindol-3-yl)methyl- succinimide (23) from methyl N-(indol-3-yl)methylsuccinamate (22) — Prepared according to the method for 19, where 95% NaBH3CN (66.0 mg, 1.00 mmol) and 22 (49.8 mg, 0.19 mmol) in AcOH (2.0 mL) were used. After usual work-up and purification, 23 (6.5 mg, 15%) and 24 (41.0 mg, 82%) were obtained. 24: mp 73.0–74.0 °C (colorless prisms, recrystallized from CH2Cl2–hexane). IR (KBr): 3290, 1726, 1638, 1609, 1542, 1483, 1433, 1338, 1197, 1174, 745 cm-1. 1H-NMR (CD3OD) δ: 2.50 (2H, t, J=6.8 Hz), 2.61 (2H, t, J=6.8 Hz), 3.25 (1H, dd, J=9.3, 5.5 Hz), 3.28–3.32 (1H, m), 3.41–3.47 (2H, m), 3.56 (1H, t, J=9.3 Hz), 3.66 (3H, s), 6.68 (1H, d, J=7.6 Hz), 6.69 (1H, td, J=7.6, 1.0 Hz), 7.00 (1H, t, J=7.6 Hz), 7.14 (1H, d, J=7.6 Hz). MS m/z: 262 (M+). Anal. Calcd for C14H18N2O3: C, 64.10; H, 6.92; N, 10.68. Found: C, 64.11; H, 6.90; N, 10.69. 23: mp 94.5–96.0 °C (colorless prisms, recrystallized from MeOH). IR (KBr): 3370, 2990, 2820, 1778, 1689, 1608, 1405, 1351, 1247, 1124, 1151, 755 cm-1. 1H-NMR (CD3OD) δ: 2.71 (4H, s), 3.29 (1H, dd, J=9.5, 5.1 Hz), 3.48 (1H, dd, J=9.5, 8.4 Hz), 3.57 (1H, m), 3.64 (1H, dd, J=13.1, 8.7 Hz), 3.71 (1H, dd, J=13.1, 5.4 Hz), 6.66 (1H, t, J=7.8 Hz), 6.68 (1H, td, J=7.3, 1.0 Hz), 7.01 (1H, m), 7.08 (1H, d, J=7.3 Hz). MS m/z: 230 (M+). Anal. Calcd for C13H14N2O2: C, 67.81; H, 6.13; N, 12.17. Found: C, 67.77; H, 6.11; N, 12.08.
Methyl N-(1-hydroxyindol-3-yl)methylsuccinamate (25a) from 24 — Prepared according to the general method B, where Na2WO4·2H2O (14.6 mg, 0.04 mmol) in H2O (0.4 mL), 24 (56.8 mg, 0.21 mmol) in MeOH (3.5 mL), and 30% H2O2 (249.9 mg, 2.21 mmol) in MeOH (1.0 mL) were used. After usual work-up and purification, 25a (37.5 mg, 63%) was obtained. 25a: mp 115.5–116.0 °C (colorless needles, recrystallized from EtOAc). IR (KBr): 3350, 3120, 2930, 1710, 1637, 1535, 1443, 1387, 1358, 1243, 1218, 1174, 735 cm-1. 1H-NMR (CD3OD) δ: 2.48 (2H, t, J=6.7 Hz), 2.62 (2H, t, J=6.7 Hz), 3.61 (3H, s), 4.48 (2H, s), 7.01 (1H, ddd, J=8.1, 7.1, 1.0 Hz), 7.15 (1H, ddd, J=8.3, 7.1, 1.0 Hz), 7.24 (1H, s), 7.36 (1H, dt, J=8.3, 1.0 Hz), 7.54 (1H, dt, J=8.1, 1.0 Hz). MS m/z: 276 (M+). Anal. Calcd for C14H16N2O4: C, 60.86; H, 5.84; N, 10.14. Found: C, 60.72; H, 5.85; N, 10.12.
Methyl N-(1-methoxyindol-3-yl)methylsuccinamate (25b) from 25a — Ethereal CH2N2 (excess) was added to a solution of 25a (25.5 mg, 0.09 mmol) in MeOH (1.0 mL) and stirring was continued at rt for 30 min. After evaporation of the solvent under reduced pressure, the residue was column-chromato- graphed on SiO2 with CH2Cl2–MeOH (99:1, v/v) to give 25b (25.5 mg, 95%). 25b: mp 75.0–76.5 °C (colorless prisms, recrystallized from CH2Cl2–hexane). IR (KBr): 3280, 1730, 1634, 1537, 1445, 1349, 1319, 1201, 1136, 736 cm-1. 1H-NMR (CD3OD) δ: 2.49 (2H, t, J=7.1 Hz), 2.62 (2H, t, J=7.1 Hz), 3.61 (3H, s), 4.05 (3H, s), 4.48 (2H, s), 7.06 (1H, ddd, J=7.8, 7.1, 1.0 Hz), 7.20 (1H, ddd, J=8.3, 7.1, 1.0 Hz), 7.36 (1H, s), 7.39 (1H, dt, J=8.3, 1.0 Hz), 7.58 (1H, dt, J=7.8, 1.0 Hz). MS m/z: 290 (M+). Anal. Calcd for C15H18N2O4: C, 62.05; H, 6.25; N, 9.65. Found: C, 62.05; H, 6.33; N, 9.60.
3-Methylthiomethylindole (27) from gramine (26) — MeI (1.45 mL, 23.3 mmol) was added to a solution of 26 (399.3 mg, 2.30 mmol) in THF (23.0 mL) and stirred at rt for 1 h. The solvent was evaporated under reduced pressure to leave a residue, which was dissolved in MeOH (20.0 mL). To the resultant solution, 15% aqueous NaSMe (10.7 mL, 23.3 mmol) was added and stirred at rt for 15 h. After addition of H2O, the whole was extracted with CH2Cl2–MeOH (95:5, v/v). The extract was washed with brine, dried over Na2SO4, and evaporated under reduced pressure to leave a residue, which was column-chromatographed on SiO2 with CHCl3–MeOH–28% aq. NH3 (100:20:2, v/v) to give 27 (325.7 mg, 80%) and 26 (65.7 mg, recovery, 17%) in the order of elution. 27: mp 91.0–92.5 °C (colorless prisms, recrystallized from CH2Cl2–hexane). IR (KBr): 3310, 1645, 1555, 1456, 1421, 1354, 1253, 1097, 745, 639 cm-1. 1H-NMR (CD3OD) δ: 1.98 (3H, s), 3.89 (2H, s), 7.00 (1H, ddd, J=8.1, 7.2, 0.9 Hz), 7.09 (1H, ddd, J=8.2, 7.2, 1.1 Hz), 7.14 (1H, s), 7.32 (1H, dd, J=8.2, 0.9 Hz), 7.62 (1H, dd, J=8.1, 1.1 Hz). Anal. Calcd for C10H11NS: C, 67.79; H, 6.25; N, 7.88. Found: C, 67.76; H, 6.25; N, 7.90.
2,3-Dihydro-3-methylthiomethylindole (28) from 27 — Prepared according to the method for 19, where 95% NaBH3CN (355.5 mg, 5.37 mmol) and 27 (100.2 mg, 0.56 mmol) in AcOH (6.0 mL) were used. After usual work-up and purification, 27 (21.8 mg, recovery, 22%) and 28 (55.5 mg, 55%) were obtained. 28: colorless oil. IR (film): 3370, 2920, 1607, 1488, 1465, 1249, 747 cm-1. 1H-NMR (CDCl3) δ: 2.15 (3H, s), 2.68 (1H, dd, J=12.8, 9.4 Hz), 2.91 (1H, dd, J=12.8, 5.1 Hz), 3.44 (1H, dd, J=9.2, 6.2 Hz), 3.49–3.55 (1H, m), 3.75 (1H, t, J=9.2 Hz), 6.68 (1H, d, J=7.6 Hz), 6.75 (1H, t, J=7.6 Hz), 7.06 (1H, t, J=7.6 Hz), 7.17 (1H, d, J=7.6 Hz). MS m/z: 179 (M+). Anal. Calcd for C10H13NS: C, 66.99; H, 7.31; N, 7.81. Found: C, 67.10; H, 7.36; N, 7.93.
1-Hydroxy-3-methylsulfinylmethylindole (29) from 28 — Prepared according to general method B, where Na2WO4·2H2O (47.5 mg, 0.14 mmol) in H2O (0.7 mL), 28 (128.9 mg, 0.72 mmol) in MeOH (6.0 mL), and 30% H2O2 (803.7 mg, 7.09 mmol) in MeOH (1.0 mL) were used. Then, a solution of Me2S (0.42 mL, 5.76 mmol) in MeOH (1.0 mL) was added to the reaction mixture. After usual work-up and purification, 29 (41.2 mg, 27%) was obtained. 29: mp 114.0–115.0 °C (pale orange prisms, recrystallized from EtOAc). IR (KBr): 2580, 1349, 1322, 1240, 1093, 1007, 947, 735 cm-1. 1H-NMR (CD3OD) δ: 2.53 (3H, s), 4.23 (1H, d, J=13.7 Hz), 4.30 (1H, d, J=13.7 Hz), 7.08 (1H, ddd, J=8.1, 7.0, 1.0 Hz), 7.20 (1H, ddd, J=8.1, 7.0, 1.0 Hz), 7.39 (1H, s), 7.42 (1H, d, J=8.1 Hz), 7.62 (1H, d, J=8.1 Hz). High resolution MS m/z: Calcd for C10H11NO2S: 209.0510. Found: 209.0508.
1-Methoxy-3-methylsulfinylmethylindole (30) and 1-methoxy-3-methylsulfonylmethylindole (31) from 28 — [Entry 1]: Prepared according to the general method B, where Na2WO4·2H2O (35.5 mg, 0.11 mmol) in H2O (0.5 mL), 28 (94.7 mg, 0.53 mmol) in MeOH (4.0 mL), and 30% H2O2 (600.3 mg, 5.30 mmol) in MeOH (1.0 mL) were used. After stirring at rt for 5 min, a solution of Me2S (0.31 mL, 4.23 mmol) in MeOH (1.0 mL) was added and stirred for 30 min. Ethereal CH2N2 (excess) was then added and stirred for 30 min. After usual work-up and purification by column-chromatography on SiO2 with CH2Cl2–MeOH (99:1, v/v), 31 (20.1 mg, 16%) and 30 (31.8 mg, 27%) were obtained. 30: mp 67.0–69.0 °C (colorless prisms, recrystallized from CH2Cl2–hexane). IR (KBr): 3420, 1453, 1435, 1349, 1321, 1093, 1063, 1025, 965, 946, 747 cm-1. 1H-NMR (CD3OD) δ: 2.54 (3H, s), 4.11 (3H, s), 4.21 (1H, dd, J=13.8, 0.6 Hz), 4.30 (1H, dd, J=13.8, 0.6 Hz), 7.13 (1H, ddd, J=8.1, 7.1, 1.0 Hz), 7.25 (1H, ddd, J=8.3, 7.1, 1.0 Hz), 7.45 (1H, dt, J=8.3, 1.0 Hz), 7.53 (1H, s), 7.66 (1H, dt, J=8.1, 1.0 Hz). MS m/z: 223 (M+). Anal. Calcd for C11H13NO2S·1/8H2O: C, 58.58; H, 5.81; N, 6.21. Found: C, 58.49; H, 5.84; N, 6.14. 31: mp 101.5–102.5 °C (colorless plates, recrystallized from CH2Cl2–hexane). IR (KBr): 3100, 2930, 1455, 1320, 1263, 1244, 1147, 1120, 968, 945, 747, 736 cm-1. 1H-NMR (CDCl3) δ: 2.75 (3H, s), 4.13 (3H, s), 4.41 (2H, s), 7.21 (1H, ddd, J=8.1, 7.1, 1.0 Hz), 7.31 (1H, ddd, J=8.1, 7.1, 1.0 Hz), 7.48 (1H, dt, J=8.1, 1.0 Hz), 7.48 (1H, s), 7.62 (1H, dt, J=8.1, 1.0 Hz). MS m/z: 239 (M+). Anal. Calcd for C11H13NO3S: C, 55.21; H, 5.48; N, 5.85. Found: C, 55.19; H, 5.47; N, 5.81.
3-Acetylthiomethylindole (33) from 26 — MeI (0.12 mL, 1.85 mmol) was added to a solution of 26 (32.2 mg, 0.19 mmol) in THF (2.0 mL) at rt and stirring was continued for 1 h. The solvent was evaporated under reduced pressure to leave a residue, which was dissolved in DMF–H2O (3:1, v/v, 2.0 mL). To the resultant solution, KSCOMe (31.7 mg, 0.28 mmol) was added and stirred at rt for 2 h. After usual work-up and purification by column-chromatography on SiO2 with CHCl3–MeOH–28% aq. NH3 (100:20:2, v/v), 33 (29.8 mg, 79%) and 26 (6.9 mg, recovery, 21%) were obtained. 33: colorless oil. IR (film): 3350, 1676, 1454, 1419, 1352, 1339, 1136, 1116, 1095, 959, 740 cm-1. 1H-NMR (CDCl3) δ: 2.34 (3H, s), 4.35 (2H, d, J=0.7 Hz), 7.14 (1H, ddd, J=8.1, 7.1, 1.0 Hz), 7.18 (1H, d, J=2.4 Hz), 7.21 (1H, ddd, J=8.1, 7.1, 1.0 Hz), 7.35 (1H, dt, J=8.1, 1.0 Hz), 7.60 (1H, d, J=8.1 Hz), 8.03 (1H, br s). High resolution MS m/z: Calcd for C11H11NOS: 205.0561. Found: 205.0541.
3-Acetylthiomethyl-2,3-dihydroindole (34) from 33 — Prepared according to the method for 19, where 95% NaBH3CN (42.6 mg, 0.64 mmol) and 33 (26.2 mg, 0.13 mmol) in AcOH–CF3CO2H (3:1, v/v, 1.5 mL) were used. After usual work-up, 34 (17.8 mg, 67%) was obtained. 34: colorless oil. IR (film): 3370, 1692, 1611, 1487, 1465, 1252, 1138, 957, 748 cm-1. 1H-NMR (CDCl3) δ: 2.36 (3H, s), 3.10 (1H, dd, J=13.6, 8.3 Hz), 3.28 (1H, dd, J=13.6, 5.4 Hz), 3.30 (1H, dd, J=9.1, 6.1 Hz), 3.48–3.53 (1H, m), 3.68 (1H, t, J=9.1 Hz), 6.65 (1H, d, J=7.5 Hz), 6.73 (1H, td, J=7.5, 1.0 Hz), 7.06 (1H, t, J=7.5 Hz), 7.19 (1H, d, J=7.5 Hz). High resolution MS m/z: Calcd for C11H13NOS: 207.0718. Found: 207.0763.

3-Acetylthiomethyl-1-methoxyindole (35) from 33 — Crude 34, prepared with 95% NaBH3CN (60.6 mg, 0.92 mmol) and 33 (37.9 mg, 0.18 mmol) in AcOH–CF3CO2H (3:1, v/v, 2.0 mL), was dissolved in MeOH (1.5 mL). To the resultant solution, a solution of Na2WO4·2H2O (12.3 mg, 0.04 mmol) in H2O (0.2 mL) and then a solution of 30% H2O2 (207.8 mg, 1.83 mmol) in MeOH (0.5 mL) were added under ice cooling and stirred at rt for 20 min. Ethereal CH2N2 (excess) was added to the mixture and stirring was continued at rt for 1 h. After usual work-up and purification, 35 (6.6 mg, 15%) was obtained. 35: colorless oil. IR (film): 2940, 1689, 1452, 1354, 1232, 1133, 1097, 1031, 954, 758, 737 cm-1. 1H-NMR (CDCl3) δ: 2.34 (3H, s), 4.06 (3H, s), 4.29 (2H, d, J=0.7 Hz), 7.13 (1H, ddd, J=8.1, 7.1, 1.0 Hz), 7.24–7.27 (2H, m), 7.43 (1H, dt, J=8.1, 1.0 Hz), 7.57 (1H, dt, J=8.1, 1.0 Hz). High resolution MS m/z: Calcd for C12H13NO2S: 235.0667. Found: 235.0685.
2,3-Dihydro-N,N-dimethylindole-3-acetamide (37a) from N,N-dimethylindole-3-acetamide (36a) — Prepared according to the method for 19, where 95% NaBH3CN (394.5 mg, 5.96 mmol) and 36a (241.1 mg, 1.20 mmol) in AcOH (10.0 mL) were used. After work-up, 37a (236.6 mg, 97%) was obtained. 37a: colorless oil. IR (film): 3310, 2930, 1630, 1488, 1465, 1407, 1322, 1254, 1143, 748 cm-1. 1H-NMR (CDCl3) δ: 2.58 (1H, dd, J=16.0, 8.9 Hz), 2.73 (1H, dd, J=16.0, 4.8 Hz), 2.94 (3H, s), 2.97 (3H, s), 3.23–3.26 (1H, m), 3.78–3.86 (2H, m), 6.65 (1H, d, J=7,7 Hz), 6.71 (1H, td, J=7.3, 1.0 Hz), 7.04 (1H, d, J=7.7 Hz), 7.10 (1H, d, J=7.3 Hz). High resolution MS m/z: Calcd for C12H16N2O: 204.1263. Found: 204.1255.
2,3-Dihydro-N,N-dimethylindole-3-propionamide (37b) from N,N-dimethylindole-3-propionamide (36b) — Prepared according to the method for 19, where 95% NaBH3CN (303.5 mg, 4.59 mmol) and 36b (201.4 mg, 0.93 mmol) in AcOH (10.0 mL) were used. After usual work-up and purification, 37b (199.8 mg, 98%) was obtained. 37b: colorless oil. IR (film): 3290, 2920, 1628, 1486, 1459, 1399, 1247, 1143, 747 cm-1. 1H-NMR (CDCl3) δ: 1.88–1.96 (1H, m), 2.11–2.18 (1H, m), 2.33–2.45 (2H, m), 2.95 (3H, s), 2.99 (3H, s), 3.24 (1H, dd, J=8.8, 6.4 Hz), 3.33–3.39 (1H, m), 3.70 (1H, t, J=8.8 Hz), 6.64 (1H, d, J=7.6 Hz), 6.72 (1H, td, J=7.6, 1.0 Hz), 7.03 (1H, d, J=7.6 Hz), 7.11 (1H, d, J=7.6 Hz). High resolution MS m/z: Calcd for C13H18N2O: 218.1419. Found: 218.1427.
N,N-Dimethyl-1-hydroxyindole-3-acetamide (38a) from 37a — Prepared according to the general method B, where Na2WO4·2H2O (131.6 mg, 0.40 mmol) in H2O (4.0 mL), 37a (407.4 mg, 2.00 mmol) in MeOH (3.0 mL), and 30% H2O2 (2.214 g, 19.5 mmol) in MeOH (5.0 mL) were used. After usual work-up, 38a (321.4 mg, 74%) was obtained. 38a: mp 146.0–147.0 °C (colorless prisms, recrystallized from CHCl3–hexane). IR (KBr): 2600, 1590, 1405, 1316, 1216, 1086, 758, 741 cm-1. 1H-NMR (CDCl3) δ: 2.97 (3H, s), 2.97 (3H, s), 3.61 (2H, s), 6.52 (1H, s), 6.98 (1H, ddd, J=8.1, 7.1, 1.0 Hz), 7.16 (1H, ddd, J=8.1, 7.1, 1.0 Hz), 7.23 (1H, d, J=8.1 Hz), 7.43 (1H, d, J=8.1 Hz), 10.72 (1H, s, D2O exchange). Anal. Calcd for C12H14N2O2: C, 66.04; H, 6.47; N, 12.84. Found: C, 65.74; H, 6.36; N, 12.69.
N,N-Dimethyl-1-hydroxyindole-3-propionamide (38b) from 37b — Prepared according to general method B, where Na2WO4·2H2O (208.4 mg, 0.63 mmol) in H2O (6.0 mL), 37b (688.0 mg, 3.16 mmol) in MeOH (55.0 mL), and 30% H2O2 (3.543 g, 31.3 mmol) in MeOH (5.0 mL) were used. After usual work-up and purification, 38b (483.9 mg, 66%) was obtained. 38b: mp 144.0–145.0 °C (colorless prisms, recrystallized from CHCl3–hexane). IR (KBr): 2760, 1598, 1402, 1310, 1140, 1026, 736 cm-1. 1H-NMR (DMSO-d6) δ: 2.63 (2H, dd, J=8.2, 7.2 Hz), 2.82 (3H, s), 2.88 (2H, dd, J=8.2, 7.2 Hz), 2.93 (3H, s), 6.97 (1H, ddd, J=8.1, 7.1, 1.0 Hz), 7.12 (1H, ddd, J=8.1, 7.1, 1.0 Hz), 7.23 (1H, s), 7.31 (1H, d, J=8.1 Hz), 7.51 (1H, d, J=8.1 Hz), 10.98 (1H, s, D2O exchange). Anal. Calcd for C13H16N2O2·1/4H2O: C, 65.94; H, 7.02; N, 11.83. Found: C, 66.14; H, 6.85; N, 11.80.
9-Hydroxy-1,2,3,4-tetrahydrocarbazole (40) from 1,2,3,4,4a,9a-hexahydrocarbazole (39) — Prepared according to general method B, where Na2WO4·2H2O (28.7 mg, 0.087 mmol) in H2O (1.0 mL), 39 (71.8 mg, 0.41 mmol) in MeOH (10.0 mL), and 30% H2O2 (0.45 mL, 3.92 mmol) were used. After usual work-up and purification, 39 (13.3 mg, 18%) and 40 (50.1 mg, 65%) were obtained. 40: yellow oil. IR (film): 3061, 2931, 2857, 1458, 1238, 1178, 740 cm-1. 1H-NMR (CD3OD) δ: 1.73–1.84 (4H, m), 2.55–2.57 (2H, m), 2.64–2.66 (2H, m), 6.83 (1H, t, J=7.9 Hz), 6.94 (1H, t, J=7.9 Hz), 7.18 (1H, d, J=7.9 Hz), 7.23 (1H, d, J=7.9 Hz). High resolution MS m/z: Calcd for C12H13NO: 187.0997. Found: 187.1001.
9-Methoxy-1,2,3,4-tetrahydrocarbazole (41) from 1,2,3,4,4a,9a-hexahydrocarbazole (39) — Prepared according to the general method B, where Na2WO4·2H2O (19.3 mg, 0.028 mmol), 39 (50.6 mg, 0.29 mmol) in MeOH (4.0 mL), and 30% H2O2 (331.6 mg, 2.92 mmol) in MeOH (1.0 mL) were used. After methylation and work-up, product purification was carried out by p-TLC on SiO2 with CH2Cl2–hexane (7:3, v/v) as a developing solvent to afford 41 (32.2 mg, 55%). 41: colorless oil. IR (KBr): 2942, 2842, 1459, 1443, 1230, 1046, 735 cm-1. 1H-NMR (CDCl3) δ: 1.68–2.08 (4H, m), 2.52–2.92 (4H, br m), 3.99 (3H, s), 6.88–7.48 (4H, m). High resolution MS m/z: Calcd for C13H15NO: 201.1152. Found: 201.1134.
9-Methoxy-1,2,3,4-tetrahydrocarbazole (41) from 40 — K2CO3 (173.3 mg, 1.25 mmol) and Me2SO4 (0.053 mL, 0.56 mmol) were added to a solution of 40 (67.0 mg, 0.33 mmol) in acetone (10.0 mL) and the mixture was stirred at rt for 2 h. After usual work-up and purification, 41 (54.8 mg, 70%) was obtained.
9-Methoxycarbazole (42) from 41 — Dichlorodicyanoquinone (469.4 mg, 2.38 mmol) was added to a solution of 41 (188. 9 mg, 0.94 mmol) in benzene (30.0 mL) and stirred at rt (14 °C) for 3 h. Precipitates were filtered off through silica gel and washed with CH2Cl2. Washings and filtrates were combined and evaporated under reduced pressure to leave a crystalline solid, which was column-chromatographed on SiO2 with hexane–EtOAc (9:1, v/v) as an eluent to afford 42 (121.1 mg, 65%). 42: mp 40.0–41.0 °C (colorless needles, recrystallized from MeOH). IR (KBr): 1601, 1450, 1320, 1233, 1052, 946 cm-1. 1H-NMR (CDCl3) δ: 4.12 (3H, s), 7.19 (1H, dd, J=7.3, 2.7 Hz), 7.25 (1H, dd, J=7.3, 2.7 Hz), 7.34–7.58 (4H, m), 8.02 (2H, dt, J=7.3, 1.0 Hz). MS m/z: 197 (M+). Anal. Calcd for C13H11NO: C, 79.17; H, 5.62; N, 7.10. Found: C, 79.36; H, 5.55; N, 7.21.
A mixture of diastereoisomers, 4-nitro-1,2,2a,3,4,5-hexahydrobenz[cd]indole (44) from 4-nitro-1,3,4,5-tetrahydrobenz[cd]indole (43) — Prepared according to the method for 19, where 95% NaBH3CN (60.8 mg, 0.97 mmol) and 43 (35.9 mg, 0.18 mmol) in AcOH–CF3CO2H (3:2, v/v, 2.0 mL) were used. After usual work-up, crude 44 was subjected to p-TLC on SiO2 with CH2Cl2–hexane (3:1, v/v) as a developing solvent. Extraction of the band having an Rf value of 0.39–0.14 with CH2Cl2–MeOH (95:5, v/v) afforded pure 44 (34.4 mg, 95%). Although 1H-NMR analysis of 44 showed 2:1 mixture of diastereoisomers, further separation was not examined.
1-Hydroxy-4-nitro-1,3,4,5-tetrahydrobenz[cd]indole (45) from a diastereoisomer’s mixture (44) — Prepared according to general procedure C, where Na2WO4·2H2O (10.5 mg, 0.03 mmol) in H2O (0.2 mL), urea·H2O2 (138.6 mg, 1.47 mmol), and diastereoisomer’s mixture, 44 (30.2 mg, 0.15 mmol), in MeOH (2.0 mL) were used. The reaction mixture was adjusted to pH 4 by adding 0.6% HCl and extracted with CH2Cl2–MeOH (95:5, v/v). After usual work-up and purification, 45 (16.9 mg, 52%) was obtained. 45: mp 134–134.5 ℃ (colorless prisms, recrystallized from CH2Cl2–hexane). IR (KBr): 3427, 3112, 2971, 1604, 1530, 1442, 1419, 1349, 1149, 1001, 848, 769, 751 cm-1. 1H-NMR (CDCl3) δ: 3.50 (2H, br s), 3.52 (1H, dd, J=15.6, 4.4 Hz), 3.61 (1H, dd, J=15.6, 9.3 Hz), 4.98 (1H, ddd, J=13.7, 9.3, 4.4 Hz), 6.79 (1H, br s, D2O exchange), 6.89 (1H, br s), 7.01 (1H, br s), 7.21 (1H, dd, J=7.8, 7.3 Hz). High resolution MS m/z: Calcd for C11H10N2O3: 218.0690. Found: 218.0692.
1-Methoxy-4-nitro-1,3,4,5-tetrahydrobenz[cd]indole (46) from 45 — Ethereal CH2N2 solution (excess) was added to a solution of 45 (7.5 mg, 0.04 mmol) in MeOH (1.0 mL) at rt with stirring for 0.5 h. After evaporation of solvent under reduced pressure, the residue was purified by p-TLC on SiO2 with CH2Cl2–hexane (1:1, v/v) as a developing solvent. Extraction of the band having an Rf value of 0.50–0.31 with CH2Cl2–MeOH (95:5, v/v) afforded 46 (5.1 mg, 64%). 46: pale brown oil. IR (KBr): 3450, 2941, 1605, 1521, 1440, 1561, 1540, 983, 761, 747 cm-1. 1H-NMR (CDCl3) δ: 3.48 (2H, dd, J=17.3, 1.0 Hz), 3.54 (1H, dd, J=15.6, 4.6 Hz), 3.61 (1H, dd, J=15.6, 9.3 Hz), 4.07 (3H, s), 4.99 (1H, ddt, J=9.3, 7.3, 4.6 Hz), 6.90 (1H, d, J J=7.3 Hz), 7.02 (1H, s), 7.20 (1H, dd, J=7.8, 7.3 Hz), 7.25 (1H, d, J=7.8 Hz). High resolution MS m/z: Calcd for C12H12N2O3: 232.0847. Found: 232.0893.
A mixture of diastereoisomers, 4-(N-phenylacetylamino)-1,2,2aβ,3,4β,5-hexahydrobenz[cd]indole (48a) and 4-(N-phenylacetylamino)-1,2,2aα,3,4β,5-hexahydrobenz[cd]indole (48b) from 4-(N-phenylacetylamino)-1,3,4,5-tetrahydrobenz[cd]indole (47) — Prepared according to the method for 19, where 95%NaBH3CN (46.0 mg, 0.73 mmol) and 47 (40.1 mg, 0.14 mmol) in AcOH–CF3CO2H (4:1, v/v, 2.0 mL) were used. After work-up and purification, 48a (17.0 mg, 47%) and 48b (16.7 mg, 41%) were obtained. 48a: colorless oil. IR (KBr) : 3261, 3037, 2910, 2843, 1637, 1603, 1532, 1491, 1452, 1333, 1247, 1233, 761, 718, 692 cm-1. 1H-NMR (CD3OD) δ: 1.45 (1H, dt, J=12.8, 3.2 Hz), 2.29 (1H, dt, J=12.8, 4.6 Hz), 2.70 (1H, d, J=18.3 Hz), 2.96 (1H, dd, J=18.3, 6.4 Hz), 3.00 (1H, dd, J=11.9, 8.3 Hz), 3.10–3.19 (1H, m), 3.46 (1H, d, J=14.2 Hz), 3.50 (1H, d, J=14.2 Hz), 3.57 (1H, dd, J=8.3, 7.3 Hz), 4.39–4.46 (1H, m), 6.51 (2H, t, J=7.3 Hz), 6.94 (1H, dd, J=8.3, 7.3 Hz), 7.19–7.24 (1H, m), 7.27 (2H, s), 7.28 (2H, s). High resolution MS m/z: Calcd for C19H20N2O: 292.1575. Found: 292.1578. 48b: mp 161–162℃ (colorless prisms, recrystallized from EtOAc–hexane). IR (KBr): 3233, 3054, 2928, 2883, 1637, 1551, 1452, 1280, 1243, 762, 727, 691 cm-1. 1H-NMR (CD3OD) δ: 1.39 (1H, q, J=11.9 Hz), 2.24 (1H, dt, J=11.9, 3.7 Hz), 2.48 (1H, dd, J=16.5, 11.9 Hz), 2.99 (1H, dd, J=11.9, 8.3 Hz), 3.06 (1H, dd, J=16.5, 6.4 Hz), 3.12–3.22 (1H, m), 3.51 (2H, s), 3.58 (1H, t, J=8.3 Hz), 4.20 (1H, ddt, J=11.9, 6.4, 3.7 Hz), 6.49 (2H, d, J=7.3 Hz), 6.91 (1H, dd, J=8.3, 7.3 Hz), 7.20–­7.26 (1H, m), 7.30 (2H, s), 7.31 (2H,s). MS m/z: 292 (M+). Anal. Calcd for C19H20N2O: C, 78.05; H, 6.90; N, 9.58. Found: C, 77.91; H, 6.92; N, 9.42.

1-Methoxy-4-(N-phenylacetylamino)-1,3,4,5-tetrahydrobenz[cd]indole (49) from a mixture of diastereoisomers, 4-(N-phenylacetylamino)-1,2,2a,3,4,5-hexahydrobenz[cd]indoles (48a, 48b) — Prepared according to general method C, where Na2WO4·2H2O (6.6 mg, 0.02 mmol) in H2O (0.2 mL), urea·H2O2 (95.2 mg, 1.01 mmol), and diastereoisomer’s mixture, 48a and 48b (29.1 mg, 0.10 mmol), in MeOH (2.0 mL) were used. To the reaction mixture, K2CO3 (247.1 mg, 1.79 mmol) and Me2SO4 (80.0 mg, 0.64 mmol) were added and stirred at rt for 1.5 h. After usual work-up and purification, 49 (12.8 mg, 40%) was obtained. 49: mp 138–139 ℃ (colorless prisms, recrystallized from CH2Cl2–hexane). IR (KBr): 3301, 3053, 2943, 1635, 1543, 1493, 1442, 1342, 985, 752, 731 cm-1. 1H-NMR (CDCl3) δ: 2.74 (1H, dd, J=15.6, 5.9 Hz), 2.90 (1H, dd, J=15.6, 5.9 Hz), 3.01 (1H, dd, J=15.6, 3.7 Hz), 3.11 (1H, dd, J=15.6, 3.7 Hz), 3.43 (2H, s), 4.05 (3H, s), 4.61–4.69 (1H, m), 5.44 (1H, br d, J=8.3 Hz), 6.79 (1H, d, J=7.3 Hz), 6.89 (1H, s), 7.03 (1H, dd, J=7.3, 1.8 Hz), 7.13–7.22 (2H, m). MS m/z: 320 (M+). Anal. Calcd for C20H20N2O2: C, 74.98; H, 6.29; N, 8.74. Found: C, 74.70; H, 6.20; N, 8.31.
A mixture of diastereoisomers, 4-N,N-di(n-propylamino)-1,2,2a,3,4,5-hexahydrobenz[cd]indole (51), from 4-N,N-di(n-propylamino)-1,3,4,5-tetrahydrobenz[cd]indole (50) — Prepared according to the method for 19, where 95% NaBH3CN (27.2 mg, 0.43 mmol) and 50 (22.0 mg, 0.09 mmol) in AcOH–CF3CO2H (2:1, v/v, 1.5 mL) were used. After usual work-up, the reaction residue was subjected to p-TLC on SiO2 with CHCl3–MeOH–aq. 30% NH3–hexane (92:10:1:1, v/v) as a developing solvent. Extraction of the band having an Rf value of 0.53–0.24 with CHCl3–MeOH–aq. 30% NH3 (46:5:0.5, v/v) afforded 51 (19.0 mg, 86%). Although 1H-NMR analysis of 51 showed 6:1 mixture of diastereoisomers, further separation was not examined.
4-N,N-Di(n-propylamino)-1-methoxy-1,3,4,5-tetrahydrobenz[cd]indole (52) from a diastereoisomer’s mixture (51) — Prepared according to general method C, where Na2WO4·2H2O (8.1 mg, 0.02 mmol) in H2O (0.2 mL), urea·H2O2 (116.8 mg, 1.24 mmol), and diastereoisomer’s mixture, 51 (30.7 mg, 0.12 mmol), in MeOH (2.0 mL) were used. Then, the reaction mixture was treated with ethereal CH2N2 (excess), followed by addition of PPh3 (319.5 mg, 1.26 mmol) under ice cooling, and the whole was stirred at rt for 20 min. After usual work-up, products were separated by p-TLC on Al2O3 with EtOAc–hexane (1:14, v/v) to give 52 (15.8 mg, 46%) and 51 (4.2 mg, 14%). 52: pale brown oil. IR (KBr): 2950, 1606, 1460, 1441, 1375, 1152, 1071, 984, 747 cm-1. 1H-NMR (pyridine-d5) δ: 0.90 (6H, t, J=7.3 Hz), 1.42 (4H, sex, J=7.3 Hz), 2.47 (4H, t, J J=7.3 Hz), 2.73 (1H, ddd, J=15.1, 12.0, 1.5 Hz), 2.92 (1H, dd, J=15.1, 4.1 Hz), 2.95 (1H, d, J=12.0 Hz), 3.02 (1H, dd, J=15.1, 4.1 Hz), 3.20–3.27 (1H, m), 3.97 (3H, s), 6.98 (1H, d, J=7.8 Hz), 7.16 (1H, d, J=1.5 Hz), 7.29 (1H, dd, J=7.8, 6.8 Hz), 7.36 (1H, d, J=7.8 Hz). High resolution MS m/z: Calcd for C18H26N2O: 286.2043. Found: 286.2044.
1-Hydroxy-Nb-acetyltryptamine (54a) from Nb-acetyl-2,3-dihydrotryptamine (53a)— Prepared according to the general method B, where Na2WO4·2H2O (66.4 mg, 0.20 mmol), 53a (205.2 mg, 1.00 mmol) in MeOH (20.0 mL), and 30% H2O2 (1.0 mL, 10.0 mmol) were used. After usual work-up and purification, 54a (121.5 mg, 55%) was obtained. 54a: mp 138.0–139.0 °C (colorless prisms, recrystallized from EtOAc). IR (KBr): 3250, 3105, 1619, 1602, 1580, 743 cm-1. UV λmaxMeOH nm (log ε): 225 (4.52), 281 (3.62), 295 (3.66). 1H-NMR (CD3OD) δ: 1.89 (3H, s), 2.89 (2H, t, J=7.3 Hz), 3.43 (2H, t, J=7.3 Hz), 6.99 (1H, dd, J=8.3, 8.3 Hz), 7.10 (1H, s), 7.12 (1H, dd, J=8.3, 8.3 Hz), 7.34 (1H, d, J=8.3 Hz), 7.52 (1H, d, J=8.3 Hz), 7.46 (1H, d, J=8.3 Hz). MS m/z: 218 (M+). Anal. Calcd for C12H14N2O2: C, 66.04; H, 6.47; N, 12.84. Found: C, 66.02; H, 6.53; N, 12.77.
1-Hydroxy-Nb-methoxycarbonyltryptamine (54b) from Nb-methoxycarbonyl-2,3-dihydrotryptamine (53b) — Prepared according to the general method B, where Na2WO4·2H2O (56.1 mg, 0.17 mmol) in H2O (1.8 mL), 53b (185.9 mg, 0.85 mmol) in MeOH (18.0 mL), and 30% H2O2 (0.86 mL, 8.42 mmol) were used. After usual work-up and purification, 54b (131.5 mg, 67%) was obtained. 54b: mp 114.0–115.0 °C (colorless needles, recrystallized from CH2Cl2–hexane). IR (KBr): 3380, 3190, 1698, 1533, 1267, 983, 751 cm-1. UV λmaxMeOH nm (log ε): 225 (4.53), 295 (3.66). 1H-NMR (CD3OD) δ: 2.89 (2H, t, J=7.5 Hz), 3.36 (2H, t, J=7.9 Hz), 3.61 (3H, s), 6.99 (1H, t, J=7.9 Hz), 7.09 (1H, s), 7.13 (1H, t, J=7.9 Hz), 7.34 (1H, d, J=7.9 Hz), 7.53 (1H, d, J=7.9 Hz). MS m/z: 234 (M+). Anal. Calcd for C12H14N2O3: C, 61.53; H, 6.02; N, 11.96. Found: C, 61.40; H, 6.02; N, 11.90.
1-Hydroxy-Nb-trifluoroacetyltryptamine (54c) from Nb-trifluoroacetyl-2,3-dihydrotryptamine (53c) — Prepared according to the general method B, where Na2WO4·2H2O (57.8 mg, 0.18 mmol) in H2O (2.2 mL), 53c (218.6 mg, 0.85 mmol) in MeOH (20.0 mL), and 30% H2O2 (984.0 mg, 8.68 mmol) in MeOH (2.0 mL) were used. After usual work-up, the crude product was purified by column-chromatography on SiO2 with CH2Cl2–MeOH (99:1, v/v) to give 54c (165.3 mg, 72%). 54c: colorless oil. IR (film): 3310, 2935, 1721, 1698, 1566, 1553, 1451, 1354, 1205, 1098, 1008, 741 cm-1. 1H-NMR (5% CD3OD in CDCl3) δ: 2.99 (2H, t, J=6.6 Hz), 3.62 (2H, q, J=6.6 Hz), 7.07 (1H, s), 7.08 (1H, t, J=8.0 Hz), 7.22 (1H, t, J=8.0 Hz), 7.38 (1H, br s), 7.44 (1H, d, J=8.0 Hz), 7.53 (1H, d, J=8.0 Hz). High resolution MS m/z: Calcd for C12H11F3N2O2: 272.0772. Found: 272.0779.
Nb,Nb-Dimethyl-1-hydroxytryptamine (54d) from Nb,Nb-dimethyl-2,3-dihydrotryptamine (53d)— Prepared according to the general method B, where Na2WO4·2H2O (132.5 mg, 0.40 mmol) in H2O (4.0 mL), 53d (378.9 mg, 1.99 mmol) in MeOH (40.0 mL), and 30% H2O2 (2.0 mL, 19.6 mmol) in MeOH (40.0 mL) were used. After usual work-up, the crude product was purified by column-chromatography on SiO2 with CHCl3–MeOH–28% aq. NH3 (46:5:0.5, v/v) to give 54d (70.5 mg, 55%). 54d: mp 179.5–180.0 °C (colorless needles, recrystallized from MeOH–H2O). IR (KBr): 2415, 1470, 1447, 1320, 1226, 838, 737 cm-1. UV λmaxMeOH nm (log ε): 223 (4.48), 292 (3.62). 1H-NMR (CD3OD) δ: 2.35 (6H, s), 2.64–2.68 (2H, m), 2.89–2.93 (2H, m), 6.99 (1H, dt, J=0.9 and 8.1 Hz), 7.09 (1H, s), 7.13 (1H, dt, J=0.9, 8.1 Hz), 7.34 (1H, dt, J=8.1, 0.9 Hz), 7.50 (1H, dt, J=8.1, 0.9 Hz). MS m/z: 204 (M+). Anal. Calcd for C12H16N2O: C, 70.56; H, 7.90; N, 13.71. Found: C, 70.35; H, 8.04; N, 13.66.
1-Hydroxy-Nb-n-propyltryptamine (54e) from Nb-n-propyl-2,3-dihydrotryptamine (53e) — Prepared according to the general method B, where Na2WO4·2H2O (56.5 mg, 0.17 mmol) in H2O (1.8 mL), 53e (173.4 mg, 0.85 mmol) in MeOH (18.0 mL), and 30% H2O2 (0.85 mL, 8.42 mmol) were used. After usual work-up, the crude product was purified by column-chromatography on SiO2 with CHCl3–MeOH–28% aq. NH3 (46:5:0.5, v/v) to give 54e (96.3 mg, 52%). 54e: mp 147.0–148.0 °C (colorless needles, recrystallized from MeOH). IR (KBr): 2960, 2840, 1970, 1515, 1447, 1343, 1322, 1221, 1089, 785, 734 cm-1. 1H-NMR (CD3OD) δ: 0.90 (3H, t, J=7.3 Hz), 1.52 (2H, sext, J=7.3 Hz), 2.63 (2H, m), 2.94 (4H, m), 6.96 (1H, dd, J=8.0, 1.1 Hz), 7.09 (1H, s), 7.11 (1H, dd, J=8.0, 1.1 Hz), 7.37 (1H, ddd, J=8.0, 1.1, 0.7 Hz), 7.50 (1H, ddd, J=8.0, 1.1, 0.7 Hz). MS m/z: 218 (M+). Anal. Calcd for C13H18N2O·1/8H2O: C, 70.80; H, 8.34; N, 12.70. Found: C, 70.91; H, 8.29; N, 12.70.
1-Methoxy-Nb-acetyltryptamine (55a) from 54a — Ethereal CH2N2 (excess) was added to a solution of 54a (51.6 mg, 0.23 mmol) and stirred at rt for 1 h. After evaporation of the solvent under reduced pressure, the residue was column-chromatographed on SiO2 with CH2Cl2–MeOH (99:1, v/v) to give 55a (46.7 mg, 85%). 55a: colorless oil. IR (film): 3280, 3075, 1650, 1551, 1451, 740 cm-1. 1H-NMR (CDCl3) δ: 1.93 (3H, s), 2.93 (2H, t, J=6.6 Hz), 3.56 (2H, dt, J=5.9, 6.6 Hz), 4.06 (3H, s), 5.66 (1H, br s, D2O exchange), 7.11 (1H, s), 7.12 (1H, br d, J=8.3 Hz), 7.26 (1H, br d, J=8.3 Hz), 7.42 (1H, d, J=8.2 Hz), 7.56 (1H, d, J=8.3 Hz). High resolution MS m/z: Calcd for C13H16N2O2: 232.1210. Found: 232.1214.
1-Methoxy-Nb-methoxycarbonyltryptamine (55b) from 54b — Ethereal CH2N2 (excess) was added to a solution of 54b (39.1 mg, 0.18 mmol) and stirred at rt for 1 h. After usual work-up and purification, 55b (34.3 mg, 83%) was obtained. 55b: colorless oil. IR (film): 3320, 2930, 1705, 1525, 1452, 1254, 737 cm-1. 1H-NMR (CDCl3) δ: 2.93 (2H, t, J=6.6 Hz), 3.49 (2H, q, J=6.6 Hz), 3.66 (3H, s), 4.06 (3H, s), 4.76 (1H, br s), 7.10 (1H, s), 7.12 (1H, dt, J=1.1, 8.0 Hz), 7.25 (1H, dt, J=1.1, 8.0 Hz), 7.42 (1H, d, J=8.0 Hz), 7.57 (1H, d, J=8.0 Hz). High resolution MS m/z: Calcd for C13H16N2O3: 248.1160. Found: 248.1163.
1-Methoxy-Nb-trifluoroacetyltryptamine (55c) from 54c — Ethereal CH2N2 (excess) was added to a solution of 54c (32.7 mg, 0.12 mmol) and stirred at rt for 1 h. After usual work-up, 55c (26.8 mg, 78%) was obtained. 55c: mp 70.5–71.0 °C (colorless prisms, recrystallized from benzene–hexane). IR (KBr): 3270, 1732, 1702, 1567, 1454, 1215, 1186, 1148, 735 cm-1. UV λmaxMeOH nm (log ε): 223 (4.53), 276 (3.68), 290 (3.69). 1H-NMR (CDCl3) δ: 3.02 (2H, t, J=6.7 Hz), 3.67 (2H, q, J=6.7 Hz), 4.07 (3H, s), 6.35 (1H, br s), 7.12 (1H, s), 7.14 (1H, t, J=8.0 Hz), 7.28 (1H, t, J=8.0 Hz), 7.44 (1H, d, J=8.0 Hz), 7.56 (1H, d, J=8.0 Hz). High resolution MS m/z: Calcd for C13H13F3N2O3: 286.0928. Found: 286.0877.
Lespedamine (Nb,Nb-Dimethyl-1-methoxytryptamine, 55d) from 54d — Ethereal CH2N2 (excess) was added to a solution of 54d (13.1 mg, 0.064 mmol) in MeOH (5.0 mL) with stirring at rt until the starting material was not detected on tlc monitoring. After usual work-up and purification, 55d (8.0 mg, 57%) was obtained. 55d: colorless oil. IR (film): 2930, 2855, 2820, 2770, 1460, 1093, 1051, 1034, 1007, 953 cm-1 (lit.18 1459 cm-1). 1H-NMR (CDCl3) δ: 2.37 (6H, s), 2.65 (2H, t, J=8.0 Hz), 2.93 (2H, t, J=8.0 Hz), 4.05 (3H, s), 7.10 (1H, dt, J=0.9, 7.8 Hz), 7.10 (1H, s), 7.23 (1H, dt, J=0.9, 7.8 Hz), 7.40 (1H, dd, J=7.8, 0.9 Hz), 7.57 (1H, dd, J=7.8, 0.9 Hz) (lit.7b,18 1H-NMR (CCl4) δ: 2.19 (6H, s), 2.32–2.96 (4H, m), 3.92 (3H, s), 6.62–7.45 (5H, m)).
Lespedamine (55d) and lespedamine-Nb-oxide (56) from 2,3-dihydro-Nb,Nb-dimethyltryptamine (53d) — Prepared according to the general method B, where Na2WO4·2H2O (15.1mg, 0.04 mmol) in H2O (0.5 mL), 53d (43.9 mg, 0.23 mmol) in MeOH (5 mL), and 30% H2O2 (0.24 mL, 2.35 mmol) were used. After methylation and work-up, the product was purified by column-chromatography on SiO2 with CHCl3–MeOH–28% aq. NH3 (46:2:0.2, v/v) to give 55d (13.1 mg, 26%) and 56 (17.0 mg, 31%) in the order of elution. 56: colorless oil. IR (film): 3420, 1644, 1453, 954, 742 cm-1. 1H-NMR (CDCl3) δ: 3.31 (6H, s), 3.37–3.40 (2H, m), 3.57–3.60 (2H, m), 4.06 (3H, s), 7.13 (1H, dt, J=1.1, 7.9 Hz), 7.18 (1H, s), 7.25 (1H, dt, J=1.1, 7.9 Hz), 7.42 (1H, ddd, J=7.9, 1.1, 0.9 Hz), 7.59 (1H, ddd, J=7.9, 1.1, 0.9 Hz). MS m/z: 234 (M+). Anal. Calcd for C13H18N2O2·MeOH: C, 63.13; H, 8.33; N, 10.52. Found: C, 63.24; H, 8.14; N, 10.74. High resolution MS m/z: Calcd for C13H18N2O2: 234.1368. Found: 234.1370.

1-Methoxy-Nb-n-propyltryptamine (55e) and 1-methoxy-Nb-methyl-Nb-n-propyltryptamine (57) from Nb-n-propyl-2,3-dihydrotryptamine (53e)— Prepared according to the general method B, where Na2WO4·2H2O (13.9 mg, 0.04 mmol) in H2O (0.4 mL), 53e (41.9 mg, 0.21 mmol) in MeOH (4.0 mL), and 30% H2O2 (0.21 mL, 2.06 mmol) were used. After work-up, the product was purified by column-chromatography on SiO2 with CHCl3–MeOH–28% aq. NH3 (46:2:0.2, v/v) to give 57 (4.6 mg, 9%) and 55e (23.3 mg, 49%) in the order of elution. 55e: pale yellow oil. IR (film): 2960, 2930, 2875, 2820, 1451, 1094, 738 cm-1. 1H-NMR (CDCl3) δ: 0.90 (3H, t, J=7.5 Hz), 1.53 (2H, sext, J=7.5 Hz), 2.63 (2H, t, J=7.5 Hz), 2.97 (4H, m), 4.05 (3H, s), 7.10 (1H, dt, J=1.1 and 8.0 Hz), 7.11 (1H, s), 7.24 (1H, dt, J=1.1, 8.0 Hz), 7.41 (1H, dt, J=8.0, 1.1 Hz), 7.59 (1H, dt, J=8.0, 1.1 Hz). High resolution MS m/z: Calcd for C14H20N2O: 232.1575. Found: 232.1575. 57: colorless oil. IR (film): 2955, 2940, 2870, 2780, 1450, 1098, 1010, 956, 736 cm–1. 1H-NMR (CDCl3) δ: 0.93 (3H, t, J=7.3 Hz), 1.58 (2H, br sext, J=7.3 Hz), 2.40 (3H, s), 2.47 (2H, br t, J=7.3 Hz), 2.75 (2H, br t, J=7.5 Hz), 2.95 (2H, br t, J=7.5 Hz), 4.05 (3H, s), 7.11 (1H, dt, J=0.9, 8.1 Hz), 7.11 (1H, s), 7.24 (1H, dt, J=0.9, 8.1 Hz), 7.40 (1H, d, J=8.1 Hz), 7.57 (1H, d, J=8.1 Hz). High resolution MS m/z: Calcd for C15H22N2O: 246.1731. Found: 246.1734.
2,3-Dihydromelatonin (59) from melatonin (58) — A solution of 58 (1.01 g, 4.35 mmol) in CF3CO2H (20.0 mL) was added to Et3SiH (0.85 mL, 5.32 mmol) and stirred at 58 °C for 1 h. After usual work-up and purification, by column-chromatography on SiO2 with CHCl3–MeOH (97:3, v/v), 59 (847.7 mg, 83%) was obtained. 59: mp 83–84 °C (colorless prisms, recrystallized from EtOAc–hexane). IR (KBr): 3550, 1645, 1550, 1495, 1360, 1220, 1110, 1025, 890, 795, 740, 690, 585, 535 cm-1. 1H-NMR (CDCl3) δ: 1.73–1.79 (1H, m), 1.94–2.03 (1H, m), 1.95 (3H, s), 3.22–3.43 (4H, m), 3.70 (1H, br t, J=8.8 Hz), 3.75 (3H, s), 5.71 (1H, br s), 6.60 (1H, d, J=8.5 Hz), 6.62 (1H, dd, J=8.5, 2.20 Hz), 6.73 (1H, d, J=2.20 Hz). Anal. Calcd for C13H18N2O2: C, 66.64; H, 7.74; N, 11.96. Found: C, 66.47; H, 7.80; N, 11.91.
1-Hydroxymelatonin (60a) from 2,3-dihydromelatonin (59) — Prepared according to the general method B, where Na2WO4·2H2O, (107.1 mg, 0.325 mmol) in H2O (3.8 mL), 59 (379.5 mg, 1.62 mmol) in MeOH (38.0 mL), and 30% H2O2 (1.8 mL, 15.9 mmol) were used. After usual work-up and purification by column-chromatographed on SiO2 with EtOAc, 60a (234.9 mg, 58%) was obtained. 60a: mp 113–114 °C (colorless prisms recrystallized from CHCl3–hexane. IR (KBr): 3600, 3200, 2900, 2850, 1610, 1560, 1480, 1360, 1280, 1260, 1215, 1170, 1095, 1035, 995, 950, 900, 823, 795, 760, 600 cm-1. 1H-NMR (CD3OD) δ: 1.91 (3H, s), 2.86 (2H, t, J=7.3 Hz), 3.42 (2H, t, J=7.3 Hz), 3.82 (3H, s), 6.80 (1H, dd, J=8.8, 2.4 Hz), 7.03 (1H, d, J=2.4 Hz), 7.07 (1H, s), 7.23 (1H, d, J=8.8 Hz). MS m/z: 248 (M+). Anal. Calcd for C13H16N2O3·1/8H2O: C, 62.32; H, 6.54; N, 11.18. Found: C, 62.20; H, 6.40; N, 11.01.
1-Methoxymelatonin (60b) from 1-hydroxymelatonin (60a) — Excess CH2N2 in Et2O was added to a solution of 60a (40.2 mg, 0.16 mmol) in MeOH (5.0 mL) at rt and stirred for 15 min. Evaporation of the solvent under reduced pressure afforded oil, which was column-chromatographed on SiO2 with CHCl3–MeOH–28% aq. NH3 (46:2:0.2, v/v) to give 60b (39.1 mg, 75%). 60b: pale yellow oil. IR (film): 3280, 2930, 1643, 1553, 1480, 1440, 1220, 1090 cm-1. 1H-NMR (5%CD3OD–CDCl3) δ: 1.93 (3H, s), 2.87 (2H, t, J=6.8 Hz), 3.53 (2H, t, J=6.8 Hz), 3.85 (3H, s), 4.04 (3H, s), 6.91 (1H, dd, J=8.9, 2.3 Hz), 7.00 (1H, d, J=2.3 Hz), 7.08 (1H, s), 7.30 (1H, dd, J=8.9, 2.3 Hz). MS m/z: 262 (M+). High resolution MS m/z: Calcd for C14H18N2O3: 262.1317. Found: 262.1331.
(dl)-2-Acetoamino-3-(1-hydroxyindol-3-yl)propanol ((dl)-62) from (dl)-2-acetoamino-3-(2,3-dihydroindol-3-yl)propanol ((dl)-61) — Prepared according to the general method B, where Na2WO4·2H2O (44.6 mg, 0.14 mmol), (dl)-61 (158.2 mg, 0.68 mmol) in MeOH (16 mL), and 30% H2O2 (0.69 mL, 6.76 mmol) were used. After usual work-up and purification, (dl)-62 (40.8 mg, 30%) was obtained. (dl)-62: colorless unstable oil. IR (film): 3265, 3110, 1629, 1547, 738 cm-1. 1H-NMR (CD3OD) δ: 1.88 (3H, s), 2.80 (1H, dd, J=14.5, 7.5 Hz), 3.00 (1H, dd, J=14.5, 6.5 Hz), 3.53 (2H, d, J=5.1 Hz), 4.14 (1H, m), 6.96 (1H, dd, J=7.6, 7.1 Hz), 7.10 (1H, s), 7.12 (1H, dd, J=7.6, 6.8 Hz), 7.32 (1H, d, J=7.1 Hz), 7.57 (1H, d, J=6.8 Hz). High resolution MS m/z: Calcd for C13H16N2O3: 248.1159. Found: 248.1146.
(dl)-2-Acetoamino-3-(1-methoxyindol-3-yl)propanol ((dl)-63) from (dl)-62) — Ethereal CH2N2 (excess) was added to a solution of (dl)-62 (32.8 mg, 0.13 mmol) in MeOH (3.0 mL) and stirring was continued at rt for 10 min. After usual work-up and purification by column-chromatography on SiO2 with CH2Cl2–MeOH (95:5, v/v), (dl)-63 (26.7 mg, 77%) was obtained. (dl)-63: mp 117–118°C (colorless prisms, recrystallized from EtOAc). IR (KBr): 3275, 3180, 3090, 1630, 1584, 1440, 1081, 1052, 757, 737 cm-1. UV λmaxMeOH nm (log ε): 223 (4.43), 278 (3.63), 291 (3.65). 1H-NMR (CDCl3) δ: 1.96 (3H, s), 2.54 (1H, br s, D2O exchange), 2.97 (2H, d, J=6.3 Hz), 3.63 (2H, dd, J=5.6, 3.9 Hz), 4.04 (3H, s), 4.08–4.38 (1H, m), 5.88 (1H, d, J=7 Hz), 7.08 (1H, dd, J=7.1, 6.8 Hz), 7.12 (1H, s), 7.23 (1H, dd, J=7.3, 6.8 Hz), 7.40 (1H, d, J=7.1 Hz), 7.60 (1H, d, J=7.3 Hz). MS m/z: 262 (M+). Anal. Calcd for C14H18N2O2: C, 64.11; H, 6.92; N, 10.68. Found: C, 63.89; H, 7.24; N, 10.54.
(S)-(+)-Nb-Acetyl-1-hydroxytryptophan methyl ester ((S)-(+)-65) from (S)-(+)-Nb-acetyl-2,3-dihydrotryptophan methyl ester ((S)-(+)-64) — Prepared according to the general method B, where Na2WO4·2H2O (40.2 mg, 0.12 mmol), (S)-(+)-64 (159.5 mg, 0.61 mmol) in MeOH (15.0 mL), and 30% H2O2 (0.62 mL, 6.09 mmol) were used. After usual work-up, the product was purified by p-TLC on SiO2 with CH2Cl2–MeOH (98:2, v/v) to give (S)-(+)-65 (89.7 mg, 53%). (S)-(+)-65: mp 116.0–117.0 °C (colorless prisms, recrystallized from MeOH–H2O). [α]D24 +11.8° (c=0.102, MeOH). IR (KBr): 3370, 3240, 1733, 1655, 1534, 745 cm-1. UV λmaxMeOH nm (log ε): 224 (4.53), 282 (3.64), 293 (3.66). 1H-NMR (5% CD3OD in CDCl3) δ: 1.90 (3H, s), 3.19 (1H, dd, J=15.0, 5.8 Hz), 3.27 (1H, dd, J=15.0, 5.2 Hz), 3.71 (3H, s), 4.86 (1H, dd, J=5.8, 5.2 Hz), 7.01 (1H, s), 7.06 (1H, t, J=8.3 Hz), 7.19 (1H, t, J=8.3 Hz), 7.42 (1H, d, J=8.3 Hz), 7.45 (1H, d, J=8.3 Hz). MS m/z: 276 (M+). Anal. Calcd for C14H16N2O4: C, 60.86; H, 5.84; N, 10.14. Found: C, 60.85; H, 5.88; N, 10.14.
(dl)-Nb-Acetyl-1-hydroxytryptophan methyl ester ((dl)-65) from (dl)-64 — Prepared under the same reaction conditions as described in the procedure for (S)-(+)-65. Yield was 73%. (dl)-65: mp 153.0–154.0 °C (decomp., colorless prisms, recrystallized from MeOH). IR (KBr): 3259, 3125, 1739, 1640, 1547, 727 cm-1. UV λmaxMeOH nm (log ε): 224 (4.55), 282 (3.65), 294 (3.68). 1H-NMR (CD3OD) δ: 1.92 (3H, s), 3.06 (1H, dd, J=13.9, 7.6 Hz), 3.28 (1H, dd, J=13.9, 5.9 Hz), 3.65 (3H, s), 4.66 (1H, dd, J=7.6, 5.9 Hz), 6.97 (1H, ddd, J=7.1, 6.8, 1.5 Hz), 7.09 (1H, s), 7.12 (1H, ddd, J=7.6, 6.8, 1.5 Hz), 7.32 (1H, dm, J=7.1 Hz), 7.47 (1H, dm, J=7.6 Hz). MS m/z: 276 (M+). Anal. Calcd for C14H16N2O4: C, 60.86; H, 5.84; N, 10.14. Found: C, 60.78; H, 5.92; N, 10.09.

(S)-(+)-Nb-Acetyl-1-methoxytryptophan methyl ester ((S)-(+)-66) from (S)-(+)-65 — Ethereal CH2N2 (excess) was added to a solution of (S)-(+)-65 (46.8 mg, 0.17 mmol) in MeOH (2.0 mL) and stirring was continued at rt for 15 min. After work-up and purification by column-chromatography on SiO2 with CH2Cl2–MeOH (98:2, v/v), (S)-(+)-66 (38.3 mg, 78%) was obtained. (S)-(+)-66: colorless oil. [α]D20 +16.8° (c=0.107, MeOH). IR (film): 3270, 1741, 1658, 1540, 736 cm-1. UV λmaxMeOH nm (log ε): 223 (4.47), 276 (3.66), 289 (3.68). 1H-NMR (CDCl3) δ: 1.97 (3H, s), 3.25 (1H, dd, J=14.6, 4.9 Hz), 3.31 (1H, dd, J=14.6, 5.4 Hz), 3.70 (3H, s), 4.05 (3H, s), 4.93 (1H, ddd, J=7.8, 5.4, 4.9 Hz), 6.03 (1H, d, J=7.8 Hz), 7.04 (1H, s), 7.11 (1H, dd, J=8.3, 7.8 Hz), 7.24 (1H, t, J=8.3 Hz), 7.40 (1H, d, J=8.3 Hz), 7.49 (1H, d, J=7.8 Hz). High resolution MS m/z: Calcd for C15H18N2O4: 290.1266. Found: 290.1296.
(dl)-Nb-Acetyl-1-methoxytryptophan methyl ester ((dl)-66) from (dl)-65 — Ethereal CH2N2 (excess) was added to a solution of (dl)-65 (40.1 mg, 0.15 mmol) in MeOH (2.0 mL) and stirring was continued at rt for 30 min. After usual work-up, (dl)-66 (35.1 mg, 83%) was obtained. (dl)-66: mp 95–96°C (colorless plates, recrystallized from MeOH-H2O). IR (KBr): 3235, 1737, 1657, 1545, 1443, 1376, 1313, 1241, 1210, 1173, 747, 741 cm-1. UV λmaxMeOH nm (log ε): 224 (4.50), 277 (3.70), 290 (3.17). 1H-NMR (CDCl3) δ: 1.97 (3H, s), 3.26 (1H, dd, J=15.1, 4.9 Hz), 3.31 (1H, dd, J=15.1, 5.4 Hz), 3.71 (3H, s), 4.05 (3H, s), 4.93 (1H, ddd, J=7.8, 5.4, 4.9 Hz), 5.88 (1H, d, J=7.8 Hz, D2O exchange), 7.04 (1H, s), 7.11 (1H, br d, J=8.3 Hz), 7.24 (1H, br d, J=8.3 Hz), 7.41 (1H, d, J=8.3 Hz), 7.49 (1H, d, J=8.3 Hz). MS m/z: 290 (M+). Anal. Calcd for C15H18N2O4: C, 62.06; H, 6.25; N, 9.65. Found: C, 62.04; H, 6.37; N, 9.52.
X-Ray analysis (Table 2) – A single crystal (0.10 x 0.20 x 0.30 mm) of (dl)-65 was obtained by recrystallization from MeOH. All measurements were made on a Rigaku AFC5R diffractometer with graphite monochromated Cu-Kα radiation (λ=1.54178 Å). Crystal data: C14H16N2O4, M=276.29, triclinic,

space group P (#2), a=8.163 (1)Å, b=12.086 (1)Å, c=8.0126 (9)Å, α=107.940 (8)°, β=109.560 (9)°, γ=73.161 (8)°, V=693.2 (1)Å3, Z=2, Dcalc=1.324 g/cm3, F(000)=292, and µ(CuKα)=7.77 cm–1. The structure was solved by direct methods using MITHRIL24 The non-hydrogen atoms were refined anisotropically. The final cycle of full-matrix least-squares refinement was based on 2685 observed reflections (I>3.00σ (I), 2θ <120.1°) and 245 variable parameters. The final refinement converged with R=0.039 and Rw=0.047.

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