English

• 1.   Introduction

  Indole is a common biologically active natural heterocyclic product.^[1] The synthesis and functionalization of indoles has been focused on by chemists for over a century.^[2-3] Recently, numerous of methods have been developed for the preparation of the derivatives of indoles and N-alkylindoles, which are typically used in nucleophilic substitution. However, the methods have been greatly confined due to the need of extreme condition and poor atom-efficiency.^[4] Transition-metal-catalyzed synthetic methods have also gained great interest.^[5] Barluenga and coworkers^[6-7] developed a Pd-catalyzed approach to indoles via a Pd-catalyzed 1, 2-dihaloarenes and imines that involves an imine α-arylation followed by an intramolecular C—N bond-forming reaction. Bähn et al.^[8-10] reported the first homogeneously catalyzed N-alkylation of indoles with alcohols in the presence of the Shvo catalyst and p-toluenesulfonamide (PTSA). Kaneda and coworkers^[11] developed an effective dehydrogenation of indolines catalyzed by hydroxy apatite-bound palladium to give the corresponding indoles. Recently, condensation of α-amino acids and carbonyl compounds with decarboxylation to generate N-alkylindoles via azomethine ylides has become a powerful tool in this area. Pan and coworkers^[12] described an impressive brønsted acid-catalyzed intermolecular decarboxylative redox amination for the synthesis of N-alkylindoles from azomethine ylides by isomerization in dioxane under reflux (Scheme 1). Nageswar et al.^[13] discovered a preparation process of 1-substituted indoles existing copper oxide nanoparticles (Scheme 1). Moreover, Song and coworkers^[14] reported a synthesis of N-β-hydr- oxyethyl pyrroles from indolines-2-carboxylic acid and electron deficient aldehydes via a domino [3+2] cycloaddition and ring-opening aromatization process without catalyst (Scheme 1).

  Scheme 1

  

  Scheme 1.  Previous work and this work

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  Herein a 2, 3-dicyano-5, 6-dichlorobenzoquinone (DDQ)- mediated metal-free facile synthesis of N-alkyl indoles via intramolecular oxidative decarboxylative redox aromatization at room temperature (Scheme 1) based on our previous work is developed.^[15] N-Alkylindoline-2-carboxylic acids were prepared conveniently from commercial available alkyl halide and indoline-2-carboxylic acids under mild conditions via intramolecular oxidative decarboxylative redox aromatization at room temperature. To the best of our knowledge, this is the first report about DDQ-mediated intramolecular oxidative decarboxylative redox aromatization reaction.^[16]

  2.   Results and discussion

  The reactions of N-benzyl-2-carboxyindoline with dioxygen or organic peroxide (Table 1, Entries 1~6) were first investigated. High yield could be achieved using di-t-butyl peroxide (DTBP) as oxidant and the yield could be further enhanced in the presence of CuBr (Table 1, Entry 3). Most polar aprotic solvents screened show good compatibility with the reaction except dimethylsulfoxide (DMSO) (Table 1, Entry 6). To avoid the use of the metal reagents, DDQ was examined because it can be employed as a mild oxidizing agent as well as a radical receptor. To our surprise, when DDQ was used, desired product was obtained with a moderate to good yield without catalyst and ligand (Table 1, Entries 7~10). In addition, we also found that solvent is a critical factor to the reaction. CH₂Cl₂ was found to be the best solvent compared with toluene, CHCl₃, DMSO and tetrahydrofuran (THF) (Table 1, Entries 7~11). Notably, the reaction time was also significantly shortened from hours to 30 min, and temperature could be reduced from reflux to room temperature.

  表 1

  

  表 1  Optimization of reaction conditions^a

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  						Entry	Cat.	Oxidant	Ligand	Solvent	Yield/%
  1	—	O2	—	Toluene	ND
  2	—	DTBP	—	Toluene	58
  3	CuBr	DTBP	TEMED	Toluene	75
  4	CuBr	TBHP	TEMED	Toluene	68
  5	CuBr	DTBP	TEA	Toluene	73
  6	CuBr	DTBP	TEMED	DMSO	ND
  7	—	DDQ	—	CH2Cl2	75
  8	—	DDQ	—	Toluene	63
  9	—	DDQ	—	CHCl3	51
  10	—	DDQ	—	THF	57
  11	—	DDQ	—	DMSO	35
  a Conditions: Entries 1~6 were carried out on a 1 mmol scale in solvents (5 mL) at 110 ℃ for 6 h with 1a (1.0 equiv.), catalyst (0.1 equiv.), oxidant (1.2 equiv.) and ligand (0.2 equiv.); Entries 7~11 were carried out on a 1 mmol scale in solvents (5 mL) at room temperature for 30 min with DDQ (1.1 equiv.); b Isolated yields. c No desired products were obtained.

  To summarize, the optimal reaction condition for 2a are using DDQ as oxidant, CH₂Cl₂ as solvent, at room temperature. With the optimal conditions in hand, other N-alkylindole compounds were also investigated. As summarized in Table 2, significant structural variations in the 2-carboxyindoline components were well tolerated and formed the corresponding N-alkylindoles in moderate to good yields (Table 2, 2a~2i). Moreover, the reaction was also applicable to N-(thiophen-2-ylmethyl)-2-carboxy- indoline and N-(furan-2-ylmethyl)-2-carboxyindoline (Table 2, 2j and 2k), with yields of 80% and 78% respectively. In addition, 2-carboxyindoline bearing different cinnamyl groups at N atom also could react with DDQ giving the corresponding products in satisfied yields, and electron-withdrawing-groups-bearing alkyl halides showed lower yields (Table 2, 2l~2s).

  表 2

  

  表 2  Synthesis of N-alkylindole 2^a

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  We further explored the application of this efficient reaction by mixing 1, 4-dibromomethylbenzene with indoline and 2-carboxyindoline in equal amounts. Interestingly, only the desired product 1, 4-bis((1H-indol-1-yl)methyl)- benzene (2t) was obtained in moderate yields in one-pot operation (Scheme 2). It is supposed that the one-pot convergent process has three completely different paths to the single product. In this one-pot process, three different predicted intermediates 1t, 6t, 7t formed divergently were oxidized by DDQ to the same product 2t convergently in three different paths.

  Scheme 2

  

  Scheme 2.  One-pot three component convergent synthetic protocol of 2t from premixed indoline and 2-carboxyindoline

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  A plausible mechanism of the above reaction is proposed as shown in Scheme 3. Initially, the oxidative decarboxylative process produces the nitrogen cation radical carboxylates 5a by single electron transfer manner, which decar-boxylates to the azomethine ylide radicals 6a and then transforms into the azomethine ylides 7a by removing a hydrogen radical from the neighboring benzylic carbon atom, and finally generate N-alkyl indoles 2a via 1, 4-proton transfer of 8a.

  Scheme 3

  

  Scheme 3.  Assumed mechanism for the DDQ-catalyzed decarboxilative oxidation

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  3.   Conclusions

  In summary, a facile and highly efficient method to N-alkyl indoles was developed. The reaction was DDQ- mediated intramolecular oxidative decarboxylative reaction from commercial readily available alkyl halide and indoline-2-carboxylic acids at room temperature. In addition, various N-alkyl substituted indole derivatives could be obtained through this reaction, thus the method will be beneficial to the preparation of many derivatives of indoles.

  4.   Experimental section

  4.1   General information

  ¹H NMR and ¹³C NMR spectra were recorded on a Bruke Avance-400 spectrometer (400 MHz and 101 MHz, respectively) using TMS as an internal standard. High-resolution mass spectra (HRMS) were carried out on a Micromass GCTTM gas chromatograph-mass spectrometer. Flash chromatography was performed on silica gel (300~400 mesh) using mixtures of petroleum ether (b.p. 60~90 ℃) and ethyl acetate as eluents. All commercial reagents were used as received without further purification unless otherwise noted. Reaction temperatures were reported as the temperatures of the bather surrounding the flasks or tubes.

  4.2   General experimental procedures for the preparation of 2a~2t

  The benzyl bromide (1 mmol) was dissolved in 5 mL of CH₂Cl₂. The solution was dropped to the solution of 2-carboxyindoline (2.2 mmol) and TEA (2.2 mmol) in 5 mL of CH₂Cl₂. The mixture was stirred for 12 h at room temperature. After that, the solution was acidified to pH 2~3 with dilute hydrochloric acid. Then the solution was washed by water (10 mL×3). The organic phase was dried over anhydrous magnesium sulfate and concentrated under vacuum to obtain crude products 1a~1t without further purification.

  DDQ was then added to the solution of 1a~1t in 10 mL of CH₂Cl₂. The suspension was stirred for 30 min at room temperature. After the reaction completed, the mixture was filtered and the filtrate was removed by vacuum distillation. The crude product was purified by column chromatography on silica gel.

  1-Benzyl-1H-indole (2a): White solid, 75% yield. m.p. 43~44 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 7.74 (d, J＝7.6 Hz, 1H), 7.39~7.30 (m, 4H), 7.28~7.16 (m, 5H), 6.64 (d, J＝3.1 Hz, 1H), 5.38 (s, 2H); ¹³C NMR (101 MHz, CDCl₃) δ: 137.6, 136.4, 128.8 (2C), 128.8, 128.3, 127.7, 126.8(2C), 121.8, 121.1, 119.6, 109.8, 101.7, 50.1; HRMS calcd for C₁₅H₁₃N 207.1048, found 207.1051.

  1-(4-Methylbenzyl)-1H-indole (2b): Yellow liquid, 65% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.69 (d, J＝7.8 Hz, 1H), 7.33 (d, J＝8.3 Hz, 1H), 7.24~7.18 (m, 1H), 7.17~7.12 (m, 4H), 7.06 (d, J＝8.0 Hz, 2H), 6.50~6.63 (m, 1H), 5.32 (s, 2H), 2.35 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 137.3, 136.3, 134.5, 129.4 (2C), 128.7, 128.2 (2C), 126.8, 121.6, 121.0, 119.5, 109.7, 101.6, 49.9, 21.1; HRMS calcd for C₁₆H₁₅N 221.1204, found 221.1209.

  1-(4-Chlorobenzyl)-1H-indole (2c): Yellow liquid, 73% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.72 (d, J＝7.6 Hz, 1H), 7.32~7.27 (m, 3H), 7.23~7.26 (m, 1H), 7.18~7.22 (m, 1H), 7.16 (d, J＝3.1 Hz, 1H), 7.07 (d, J＝8.4 Hz, 2H), 6.62 (d, J＝3.1 Hz, 1H), 5.32 (s, 2H); ¹³C NMR (101 MHz, CDCl₃) δ: 136.2, 136.1, 133.5 (2C), 129.0, 128.8 (2C), 128.2, 128.1, 121.9, 121.1, 119.8, 109.6, 102.0, 49.5; HRMS calcd for C₁₅H₁₂ClN 241.0658, found 241.0650.

  1-(4-Nitrobenzyl)-1H-indole (2d): Yellow liquid, 67% yield. ¹H NMR (400 MHz, CDCl₃) δ: 8.15 (d, J＝8.7 Hz, 2H), 7.68~7.80 (m, 1H), 7.24~7.20 (m, 5H), 7.18 (d, J＝3.3 Hz, 1H), 6.66 (d, J＝3.2 Hz, 1H), 5.45 (s, 2H); ¹³C NMR (101 MHz, CDCl₃) δ: 147.5, 145.1, 136.1, 128.9, 128.1, 127.3 (2C), 124.1 (2C), 122.2, 121.3, 120.1, 109.4, 102.7, 49.5; HRMS-ESI calcd for C₁₅H₁₃N₂O₂ [M+H]⁺ 253.0899, found 253.0889.

  4-((1H-Indol-1-yl)methyl)benzonitrile (2e): Yellow liquid, 69% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.73 (d, J＝7.5 Hz, 1H), 7.58 (d, J＝8.1 Hz, 2H), 7.22 (s, 2H), 7.21~7.19 (m, 1H), 7.18~7.15 (m, 3H), 6.66 (d, J＝3.0 Hz, 1H), 5.40 (s, 2H); ¹³C NMR (101 MHz, CDCl₃) δ: 143.1, 136.1, 132.6 (2C), 128.9, 128.2, 127.2 (2C), 122.2, 121.3, 120.0, 118.6, 111.5, 109.5, 102.5, 49.6; HRMS calcd for C₁₆H₁₂N₂ 232.1000, found 232.1003.

  1-(3-Nitrobenzyl)-1H-indole (2f): Yellow liquid, 77% yield. ¹H NMR (400 MHz, CDCl₃) δ: 8.14 (d, J＝8.2 Hz, 1H), 8.07 (s, 1H), 7.72 (d, J＝7.7 Hz, 1H), 7.46 (t, J＝7.9 Hz, 1H), 7.35 (d, J＝7.6 Hz, 1H), 7.24~7.18 (m, 4H), 6.66 (d, J＝2.5 Hz, 1H), 5.43 (s, 2H); ¹³C NMR (101 MHz, CDCl₃) δ: 148.6, 139.9, 136.1, 132.6, 129.9, 128.9, 128.1, 122.8, 122.2, 121.6, 121.3, 120.0, 109.4, 102.7, 49.4; HRMS-ESI calcd for C₁₅H₁₃N₂O₂ [M+H]⁺ 253.0899, found 253.0890.

  2-((1H-Indol-1-yl)methyl)benzonitrile (2g): Yellow liquid, 73% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.76~7.72 (m, 2H), 7.40~7.49 (m, 1H), 7.38 (t, J＝7.2 Hz, 1H), 7.30 (d, J＝8.0 Hz, 1H), 7.22~7.28 (m, 1H), 7.24~7.21 (m, 2H), 6.85 (d, J＝7.7 Hz, 1H), 6.67 (d, J＝3.1 Hz, 1H), 5.58 (s, 2H); ¹³C NMR (101 MHz, CDCl₃) δ: 141.4, 136.2, 133.4, 133.0, 128.9, 128.4, 128.2, 127.5, 122.2, 121.3, 120.0, 117.3, 110.7, 109.5, 102.65, 48.2; HRMS calcd for C₁₆H₁₂N₂ 232.1000, found 232.1005.

  1-(4-Fluorobenzyl)-1H-indole (2h): Yellow liquid, 61% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.72 (d, J＝7.7 Hz, 1H), 7.31 (d, J＝8.2 Hz, 1H), 7.23~7.29 (m, 1H), 7.22~7.19 (m, 1H), 7.17 (d, J＝3.1 Hz, 1H), 7.07~7.15 (m, 2H), 7.05~7.00 (m, 2H), 6.63~6.60 (m, 1H), 5.33 (s, 2H); ¹³C NMR (101 MHz, CDCl₃) δ: 162.2 (d, J＝246.1 Hz), 136.2, 133.3 (d, J＝3.4 Hz), 128.8, 128.4 (d, J＝8.1 Hz, 2C), 128.1, 121.8, 121.1, 119.7, 115.7 (d, J＝21.8 Hz, 2C), 109.6, 101.9, 49.4; HRMS calcd for C₁₅H₁₂FN 225.0954, found 225.0952.

  1-(3, 5-Dimethoxybenzyl)-1H-indole (2i): White liquid, 62% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.72 (d, J＝7.8 Hz, 1H), 7.36 (d, J＝8.1 Hz, 1H), 7.24 (t, J＝7.1 Hz, 1H), 7.20~7.1 (m, 2H), 6.62 (d, J＝3.10 Hz, 1H), 6.40~6.48 (m, 1H), 6.34 (d, J＝2.12 Hz, 2H), 5.29 (s, 2H), 3.76 (s, 6H); ¹³C NMR (101 MHz, CDCl₃) δ: 161.2, 140.1, 136.5, 128.8, 128.3, 121.8, 121.0, 119.6, 109.7, 105.0 (3C), 101.8, 99.3, 55.3 (2C), 50.2; HRMS calcd for C₁₇H₁₇NO₂ 267.1259, found 269.1257.

  1-(Thiophen-2-ylmethyl)-1H-indole (2j): Yellow liquid, 80% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.69 (d, J＝7.8 Hz, 1H), 7.43 (d, J＝8.2 Hz, 1H), 7.25 (d, J＝8.1 Hz, 2H), 7.18 (dd, J＝13.2, 5.2 Hz, 2H), 6.97 (d, J＝3.1 Hz, 2H), 6.59 (d, J＝2.9 Hz, 1H), 5.50 (s, 2H); ¹³C NMR (101 MHz, CDCl₃) δ: 140.1, 136.0, 128.8, 127.6, 127.0, 125.9, 125.4, 121.8, 121.1, 119.7, 109.5, 102.1, 45.1; HRMS calcd for C₁₃H₁₁NS 213.0612, found 263.0610.

  1-(Furan-2-ylmethyl)-1H-indole (2k): Yellow liquid, 78% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.70 (d, J＝7.8 Hz, 1H), 7.47 (d, J＝8.2 Hz, 1H), 7.40 (s, 1H), 7.28 (t, J＝7.6 Hz, 1H), 7.18 (dd, J＝9.5, 5.3 Hz, 2H), 6.58 (d, J＝3.0 Hz, 1H), 6.35 (d, J＝1.1 Hz, 1H), 6.27 (d, J＝2.6 Hz, 1H), 5.30 (s, 2H); ¹³C NMR (101 MHz, CDCl₃) δ：150.5, 142.6, 136.1, 128.7, 127.8, 121.8, 121.0, 119.6, 110.5, 109.5, 108.1, 101.8, 43.2; HRMS calcd for C₁₃H₁₁NO 197.0841, found 197.0843.

  1-Cinnamyl-1H-indole (2l): Yellow liquid, 72% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.71 (d, J＝7.8 Hz, 1H), 7.44 (d, J＝8.2 Hz, 1H), 7.32~7.40 (m, 4H), 7.30~7.24 (m, 2H), 7.14~7.22 (m, 2H), 6.60 (d, J＝3.1 Hz, 1H), 6.53 (d, J＝15.9 Hz, 1H), 6.33~6.44 (m, 1H), 4.87~5.00 (m, 2H); ¹³C NMR (101 MHz, CDCl₃) δ: 135.2, 135.1, 131.3 (2C), 127.7, 127.6 (2C), 126.8, 126.7, 125.4, 123.8, 120.6, 119.9, 118.4, 108.6, 100.5, 47.3; HRMS calcd for C₁₇H₁₅N 233.1204, found 233.1205.

  1-(3-p-Tolylallyl)-1H-indole (2m): Yellow liquid, 61% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.69 (d, J＝7.8 Hz, 1H), 7.43 (d, J＝8.1 Hz, 1H), 7.31~7.26 (m, 2H), 7.20~7.12 (m, 4H), 6.57 (s, 1H), 6.51 (d, J＝15.9 Hz, 1H), 6.33 (dt, J＝15.6, 5.6 Hz, 1H), 4.92 (d, J＝5.7 Hz, 2H), 2.36 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 137.8, 133.5, 132.3, 129.3, 129.3 (2C), 128.7, 127.8, 126.4 (2C), 123.8, 121.6, 121.0, 119.4, 109.7, 101.5, 48.5, 21.2; HRMS calcd for C₁₈H₁₇N 247.1361, found 247.1365.

  1-(4-Methoxyphenyl)allyl)-1H-indole (2n): Yellow liquid, 68% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.69 (d, J＝7.8 Hz, 1H), 7.43 (d, J＝8.2 Hz, 1H), 7.30 (d, J＝8.5 Hz, 2H), 7.24 (t, J＝7.6 Hz, 1H), 7.19 (d, J＝2.7 Hz, 1H), 7.15 (t, J＝7.4 Hz, 1H), 6.86 (d, J＝7.9 Hz, 2H), 6.57 (d, J＝2.7 Hz, 1H), 6.49 (d, J＝15.8 Hz, 1H), 6.24 (dt, J＝15.6, 5.9 Hz, 1H), 4.91 (d, J＝5.9 Hz, 2H), 3.82 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 159.4, 136.1, 131.9, 129.0, 128.7, 127.8, 127.7 (2C), 122.6, 121.6, 121.0, 119.4, 114.0 (2C), 109.7, 101.4, 55.3, 48.5; HRMS calcd for C₁₈H₁₇NO 263.1310, found 263.1312.

  1-(3-(o-Tolyl)allyl)-1H-indole (2o): Yellow liquid, 70% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.57 (d, J＝7.6 Hz, 1H), 7.31 (t, J＝8.1 Hz, 2H), 7.15 (d, J＝11.0 Hz, 1H), 7.09 (s, 4H), 7.06 (s, 1H), 6.63 (d, J＝15.6 Hz, 1H), 6.46 (s, 1H), 6.13 (dd, J＝15.2, 5.9 Hz, 1H), 4.83 (d, J＝5.3 Hz, 2H), 2.19 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 136.2, 135.6, 135.5, 130.6, 130.4, 128.9, 127.9, 127.8, 126.2, 126.2, 125.9, 121.7, 121.1, 119.6, 109.7, 101.6, 48.8, 19.8; HRMS calcd for C₁₈H₁₇N 247.1361, found 247.1364.

  1-(3-(4-Chlorophenyl)allyl)-1H-indole (2p): Yellow liquid, 60% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.65 (d, J＝7.7 Hz, 1H), 7.36 (d, J＝8.2 Hz, 1H), 7.24 (s, 4H), 7.20 (d, J＝8.1 Hz, 1H), 7.14 (s, 1H), 7.11 (d, J＝7.7 Hz, 1H), 6.54 (s, 1H), 6.40 (d, J＝16.0 Hz, 1H), 6.32 (d, J＝16.0 Hz, 1H), 4.89 (s, 2H); ¹³C NMR (101 MHz, CDCl₃) δ: 147.0, 142.7, 136.1, 130.2, 129.8, 128.8, 127.9, 127.1 (2C), 123.9 (2C), 121.9, 121.2, 119.8, 109.5, 102.0, 48.1; HRMS-EI calcd for C₁₇H₁₄ClN 267.0815, found 267.0816.

  1-(3-(4-Fluorophenyl)allyl)-1H-indole (2q): Yellow liquid, 62% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.65 (d, J＝7.8 Hz, 1H), 7.35 (d, J＝8.2 Hz, 1H), 7.24 (dd, J＝8.7 Hz, 5.5 Hz, 2H), 7.21~7.17 (m, 1H), 7.14~7.09 (m, 2H), 6.94 (t, J＝8.7 Hz, 2H), 6.53 (d, J＝3.1 Hz, 1H), 6.38 (d, J＝15.9 Hz, 1H), 6.21 (dt, J＝15.8 Hz, 5.7 Hz, 1H), 4.83 (dd, J＝5.7 Hz, 1.0 Hz, 2H); ¹³C NMR (101 MHz, CDCl₃) δ: 163.7, 161.3, 136.2, 132.5(d, J＝3.5 Hz), 131.1, 128.8, 128.1 (d, J＝8.0 Hz), 127.8, 124.8 (d, J＝5.1 Hz), 121.7, 121.1, 119.6, 115.5 (dd, J＝21.4, 7.0 Hz, 2C), 109.7, 101.7, 48.3; HRMS calcd for C₁₇H₁₄FN 251.1110, found 251.1112.

  1-(3-(4-Nitrophenyl)allyl)-1H-indole (2r): Yellow liquid, 65% yield. ¹H NMR (400 MHz, CDCl₃) δ: 8.12 (d, J＝8.2 Hz, 2H), 7.67 (d, J＝7.8 Hz, 1H), 7.40 (d, J＝8.3 Hz, 2H), 7.34 (d, J＝8.1 Hz, 1H), 7.23 (d, J＝6.9 Hz, 1H), 7.17 (d, J＝11.5 Hz, 1H), 7.12 (d, J＝11.8 Hz, 1H), 6.74~6.61 (m, 1H), 6.54 (d, J＝28.0 Hz, 1H), 6.39 (d, J＝15.9 Hz, 1H), 4.94 (d, J＝3.9 Hz, 2H); ¹³C NMR (101 MHz, CDCl₃) δ: 147.0, 142.7, 136.1, 130.2, 129.8, 128.8, 127.9, 127.1, 123.9 (2C), 121.9 (2C), 121.2, 119.8, 109.5, 102.0, 48.1; HRMS-ESI calcd for C₁₇H₁₅N₂O₂ [M+H]⁺ 279.1134, found 279.1130.

  1-(3-(3-Chlorophenyl)allyl)-1H-indole (2s): Yellow liquid, 61% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.72 (d, J＝7.8 Hz, 1H), 7.41 (d, J＝8.2 Hz, 1H), 7.35 (s, 1H), 7.30~7.27 (m, 1H), 7.26~7.24 (m, 2H), 7.23~7.21 (m, 1H), 7.19 (s, 1H), 7.19~7.16 (m, 1H), 6.61 (d, J＝3.1 Hz, 1H), 6.39 (d, J＝3.2 Hz, 2H), 4.93 (d, J＝3.4 Hz, 2H); ¹³C NMR (101 MHz, CDCl₃) δ: 137.0, 134.9, 133.5, 129.7, 128.7, 127.5, 126.7 (2C), 125.5, 125.4, 123.6, 120.6, 119.9, 118.5, 108.5, 100.6, 47.1; HRMS-ESI calcd for C₁₇H₁₅ClN [M+H]⁺ 268.0893, found 268.0876

  1, 4-Bis((1H-indol-1-yl)methyl)benzene (2t): White solid, 52% yield. m.p. 124~126 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 7.67 (d, J＝7.7 Hz, 2H), 7.28 (s, 2H), 7.21~7.16 (m, 2H), 7.14 (dd, J＝9.8, 2.2 Hz, 4H), 7.05 (s, 4H), 6.57 (d, J＝3.0 Hz, 2H), 5.31 (s, 4H); ¹³C NMR (101 MHz, CDCl₃) δ: 137.0, 128.7, 128.2, 127.2, 121.7, 121.0, 119.6, 109.6, 101.8, 49.7; HRMS calcd for C₂₄H₂₀N₂ 336.1626, found 336.1625.

  Supporting Information    ¹H NMR and ¹³C NMR spectra of products 2a~2t. The Supporting Information is available free of charge via the Internet at http://sioc-journal.cn.

  
  
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• 

  Scheme 1  Previous work and this work

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  Scheme 2  One-pot three component convergent synthetic protocol of 2t from premixed indoline and 2-carboxyindoline

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  Scheme 3  Assumed mechanism for the DDQ-catalyzed decarboxilative oxidation

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  表 1  Optimization of reaction conditions^a

  						Entry	Cat.	Oxidant	Ligand	Solvent	Yield/%
  1	—	O2	—	Toluene	ND
  2	—	DTBP	—	Toluene	58
  3	CuBr	DTBP	TEMED	Toluene	75
  4	CuBr	TBHP	TEMED	Toluene	68
  5	CuBr	DTBP	TEA	Toluene	73
  6	CuBr	DTBP	TEMED	DMSO	ND
  7	—	DDQ	—	CH2Cl2	75
  8	—	DDQ	—	Toluene	63
  9	—	DDQ	—	CHCl3	51
  10	—	DDQ	—	THF	57
  11	—	DDQ	—	DMSO	35
  a Conditions: Entries 1~6 were carried out on a 1 mmol scale in solvents (5 mL) at 110 ℃ for 6 h with 1a (1.0 equiv.), catalyst (0.1 equiv.), oxidant (1.2 equiv.) and ligand (0.2 equiv.); Entries 7~11 were carried out on a 1 mmol scale in solvents (5 mL) at room temperature for 30 min with DDQ (1.1 equiv.); b Isolated yields. c No desired products were obtained.

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  表 2  Synthesis of N-alkylindole 2^a

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•