FULL PAPER DOI: 10.1002/asia.201402274
Palladium-Catalyzed Direct C2 Arylation of N-Substituted Indoles with 1Aryltriazenes Can Liu,[a] Tao Miao,[a] Lei Zhang,[a] Pinhua Li,[a] Yicheng Zhang,[a] and Lei Wang*[a, b] Abstract: A novel and efficient palladium-catalyzed C2 arylation of N-substituted indoles with 1-aryltriazenes for the synthesis of 2-arylindoles was developed. In the presence of BF3·OEt2 and palladium(II) acetate (PdACHTUNGRE(OAc)2), N-substituted indoles reacted with 1-aryltriazenes in N,N-dimethylacetamide (DMAC) to afford the corresponding aryl–indole-type products in good to excellent yields.
Introduction
a series of different functionalities after treatment with the appropriate reagents.[11] In addition, they also have been employed as electrophilic partners in transition-metal-catalyzed carbon–carbon cross-coupling reactions. For example, Sengupta et al. disclosed that aromatic triazenes were good coupling partners in Heck-type reactions.[12] Subsequently, Brse et al. extended their methodology to solid-phase organic synthesis.[13] Tamao et al. developed a palladium-catalyzed cross-coupling reaction of 1-aryltriazenes with arylboronic acids and aryltrifluorosilanes under mild reaction conditions.[14] However, the application of 1-aryltriazenes in the reaction of direct CH arylation of heteroaromatics is still unexplored. Herein, we wish to report a new and practical method for the synthesis of 2-arylindoles through palladiumcatalyzed C2 arylation of N-substituted indoles with 1-aryltriazenes in the presence of boron trifluoride, thereby providing the desired aryl–indole-type products in good to excellent yields (Scheme 1).
The arylation of indoles has been and continues to be a focus of research efforts for synthetic organic chemists because the arylated indoles are important building blocks in natural products, pharmaceuticals, and synthetic functional materials.[1] Over the past several years, the transitionmetal-catalyzed direct CH arylation of indoles with activated arenes has been successfully achieved, which provides an efficient approach for the straightforward synthesis of aryl– indole units without the need for prior functionalization of indoles (i.e., halogenation or stoichiometric metalation).[2] A variety of arylating agents, including organic halides,[3] organoboranes,[4] hypervalent iodines,[5] arylsiloxanes,[6] aromatic carboxylic acids,[7] and arenes[8] have been explored in the direct arylation reaction of indoles. More recently, we and others reported that arylsulfinic acids (salts) were good coupling partners in the direct C-arylation of indoles in the presence of palladium catalyst.[9] Despite remarkable advances in this type of transformation, the establishment of new and efficient synthetic methods for the preparation of aryl– indoles with high selectivity at the 2-position (not at the 3position) from readily available and simple aryl sources is highly desirable from both scientific and practical standpoints. Aromatic triazenes, which are very useful and versatile intermediates in organic synthesis, can be readily prepared from the corresponding arylamines by means of a simple one-step procedure.[10] They also can be converted into
Scheme 1. Pd-catalyzed C2 arylation of indoles with 1-aryltriazenes.
Results and Discussion In our initial study, N-methylindole (1 a) and 1-(p-tolyl)triazene (2 a) were chosen as model substrates to survey the reaction parameters. It was found that the catalysts, additives, and solvents play a critical role in the model reaction. Boron trifluoride (BF3) is an efficient reagent to enhance the reactivity of aryltriazenes in palladium-catalyzed crosscoupling reactions.[14a] We also attempted this arylated reaction using boron trifluoride as an additive to promote the reaction. As shown in Table 1, when palladium(II) acetate (PdACHTUNGRE(OAc)2) was used as a catalyst with BF3·OEt2 as an addi-
[a] C. Liu, T. Miao, L. Zhang, Prof. P. Li, Y. Zhang, Prof. L. Wang Department of Chemistry, Huaibei Normal University Huaibei, Anhui 235000 (P.R. China) Fax: (+ 86) 561-3090518 E-mail: [email protected] [b] Prof. L. Wang State Key Laboratory of Organometallic Chemistry Shanghai Institute of Organic Chemistry Shanghai 200032 (P.R. China) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/asia.201402274.
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Keywords: arylation · crosscoupling · heterocycles · homogeneous catalysis · palladium
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ACHTUNGRE(PPh3)2Cl2]) gave inferior results (Table 1, entries 17–20). When the catalyst loading was reduced from 2.5 to 1.0 mol %, the reaction afforded the desired product in 48 % yield (Table 1, entry 21). However, N-methylindole (1 a) did not react with 1-(p-tolyl)triazene (2 a) in the absence of either the palladium catalyst or the Lewis acid additive. It was indicated that PdACHTUNGRE(OAc)2 and BF3·OEt2 were essential for the direct C2 arylation of N-substituted indoles with 1aryltriazenes (Table 1, entries 22 and 23). Although aryldiazonium salts, as a precursor of 1-aryltriazenes, have been widely used as aryl reagents in organic synthesis, only 30 % yield of 3 a was obtained when p-tolyldiazonium tetrafluoroborate was employed in the reaction with 1 a under standard reaction conditions (Table 1, entry 24). With the optimized reaction conditions (2.5 mol % of PdACHTUNGRE(OAc)2, BF3·OEt2 (1 equiv), DMAC, 80 8C, 12 h) in hand, this Pd-catalyzed direct C2 arylation of indole was then extended to a wide array of 1-aryltriazenes and various indoles to explore the scope and limitation of the reaction. As can be seen from Scheme 2, the reactions of N-methylindole (1 a) with a wide range of 1-aryltriazenes proceeded well and generated the desired products in good to excellent yields. 1-Aryltriazenes with electron-rich groups, including methyl, ethyl, isopropyl, methoxy, and ethoxy on the benzene rings reacted with 1 a efficiently and afforded the desired products 3 a–j in 81–95 % yields. In contrast, the electron-deficient 1-aryltriazenes presented relatively lower reactivity, and the corresponding arylated products 3 k and 3 l were obtained in 74 and 65 % yields, respectively. It is notable that the steric-hindrance effect was not clear when ortho-substituted 1-aryltriazene was used as one of the substrates in the reaction (3 d, 82 % yield).[4b, 5a] Meanwhile, triazenes that bear cyclic side chains, such as five-membered pyrrolidine and six-membered piperidine, were also good substrates for this arylation reaction and generated the product 3 a in 87 and 82 % yields. The substrate scope with respect to indoles was also investigated. A series of functional groups, such as methyl, methoxy, fluoro, chloro, bromo, and ester were tolerated under the optimal reaction conditions, and the desired products 3 m–u were obtained in 57–85 % yields. It should be noted that N-ethylindole, N-propylindole, N-butylindole, and Nbenzylindole also reacted with 1-aryltriazenes efficiently, and the corresponding products 3 v–y were obtained in 77– 87 % yields. Furthermore, some steric bulk indoles, such as 1,3-dimethylindole, 1-ethyl-3-methylindole, and 1-butyl-3methylindole were arylated with 2 a smoothly to generate 3 z, 3 aa, and 3 ab in 95, 89, and 87 % yields, respectively. Although the mechanism of this reaction has not been clear up to now, on the basis of previous literature[3a, l, 9, 14a] and the above observations, we propose a possible pathway as shown in Scheme 3. In the presence of BF3·OEt2, the formed triazene–BF3 complex A is followed by the generation of arenediazonium salt B.[11b] Then, oxidative addition of the ArN bond in an arenediazonium salt (B) with in situ generated Pd0 affords an arylpalladium cation C, which reacts with 1 a in the C2-position, thereby providing inter-
Table 1. Palladium-catalyzed direct C2 arylation of N-methylindole with 1-(p-tolyl)triazene under various conditions.[a]
Entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Pd catalyst
Additive
Solvent
PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 [PdACHTUNGRE(PPh3)4] ACHTUNGRE[Pd2ACHTUNGRE(dba)3] PdCl2 [PdACHTUNGRE(CH3CN)2Cl2] [PdACHTUNGRE(PPh3)2Cl2] PdACHTUNGRE(OAc)2 – PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2
BF3·OEt2 BF3·OEt2 BF3·OEt2 BF3·OEt2 BF3·OEt2 BF3·OEt2 BF3·OEt2 BF3·OEt2 BF3·OEt2 BF3·OEt2 BF3·OEt2 BF3·OEt2 FeCl3 CuCl2 AlCl3 BF3·OEt2 BF3·OEt2 BF3·OEt2 BF3·OEt2 BF3·OEt2 BF3·OEt2 BF3·OEt2 – BF3·OEt2
DMF DMAC NMP DMSO CH3OH CH3CO2H CH3CN toluene dioxane THF CH2Cl2 DCE DMAC DMAC DMAC DMAC DMAC DMAC DMAC DMAC DMAC DMAC DMAC DMAC
Yield [%][b] 60 92 80 64 NR[c] NR 11 trace NR NR NR NR NR NR NR 73 60 50 47 27 48[d] NR NR 30[e]
[a] Reaction conditions: 1 a (0.50 mmol), 2 a (0.60 mmol), Pd catalyst (2.5 mol %), additive (0.50 mmol), solvent (2.0 mL), 80 8C, 12 h. [b] Isolated yield. [c] NR = no reaction. [d] 1.0 mol % PdACHTUNGRE(OAc)2 was used. [e] pTolyldiazonium tetrafluoroborate was used as substrate instead of 2 a.
tive and DMF as a solvent, the reaction of 1 a with 2 a generated the corresponding arylated product, 3 a, in 60 % yield (Table 1, entry 1). Much to our pleasure, 92 % isolated yield of 3 a was obtained when N,N-dimethylacetamide (DMAC) was used as solvent instead of DMF (Table 1, entry 2). Further screening of solvents revealed that DMAC was the best solvent, and other polar solvents, such as N-methyl-2-pyrrolidone (NMP) and DMSO were also effective and provided 3 a in good yields, but ethanol and acetic acid were harmful to this arylation (Table 1, entries 3–6). Several low-polar solvents including acetonitrile, toluene, dioxane, dichloroethane (DCE), dichloromethane, and tetrahydrofuran (THF) were also examined; all of them were improper solvents and the model reaction was almost prohibited (Table 1, entries 7–12). The effect of a Lewis acid was investigated on the model reaction by using FeCl3, CuCl2, and AlCl3 in place of BF3·OEt2, and the results showed that no desired product 3 a was obtained (Table 1, entries 13–15). Among the palladium species tested, [PdACHTUNGRE(PPh3)4] exhibited good activity, and 3 a was isolated in 73 % yield (Table 1, entry 16), whereas other palladium catalysts (i.e., [Pd2ACHTUNGRE(dba)3] (dba = dibenzylideneacetone), PdCl2, [PdACHTUNGRE(CH3CN)2Cl2], [Pd&
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Scheme 3. The proposed reaction mechanism.
Conclusion In summary, we have developed a palladium-catalyzed efficient method for the direct C2 arylation of indoles with 1-aryltriazenes in the presence of BF3·OEt2. To the best of our knowledge, this is the first CH arylation of indoles using 1aryltriazenes as the aryl source by means of a Pd-catalyzed cross-coupling process. This new arylation provides an alternative means of access to a broad spectrum of C2 arylated indoles in good to excellent yields. The investigation of a detailed reaction mechanism and 1-aryltriazenes as coupling species in other reactions is underway.
Experimental Section General All 1H and 13C NMR spectra were recorded with 400 MHz Bruker FTNMR spectrometers (400 or 100 MHz, respectively). All chemical shifts are given as d values [ppm] with reference to tetramethylsilane (TMS) as an internal standard. The chemicals and solvents were purchased from commercial suppliers either from Aldrich, USA or the Shanghai Chemical Company, China. Products were purified by flash chromatography on 100–200 mesh silica gels (SiO2). Typical procedure for synthetic aryltriazenes[11b] A solution of primary arylamine (4.0 mmol) in HCl (aqueous, 37 %, 2.0 mL) was cooled in an ice bath while a solution of NaNO2 (310 mg, 4.5 mmol) in cold water (8.0 mL) was added dropwise. The resulting solution of the diazonium salt was stirred at 0 8C for 30 min and then added to a solution of diethylamine (1.46 g, 20.0 mmol) and K2CO3 (6.91 g, 50.0 mmol) in acetonitrile/water (1:2, 20.0 mL) in one portion. The reaction mixture was allowed to warm to room temperature and stirred for 30 min. The aqueous phase was extracted with ethyl acetate (3 10 mL). The organic phase was washed twice with brine, dried with MgSO4, and concentrated under reduced pressure. The crude product was purified by flash column chromatography over silica gel to give the corresponding aryltriazene.
Scheme 2. Palladium-catalyzed direct C2 arylation of N-substituted indoles with 1-aryltriazenes.[a] Reaction conditions: a) 1 (0.50 mmol), 2 (0.60 mmol), PdACHTUNGRE(OAc)2 (2.5 mol %), BF3·OEt2 (0.50 mmol), DMAC (2.0 mL), 80 8C, 12 h. b) Yields of isolated products. c) 1-(Phenyldiazenyl)pyrrolidine was used instead of 2 a. d) 1-(Phenyldiazenyl)piperidine was used instead of 2 a.
Typical procedure for the C2 arylation of N-substituted indoles A 10 mL sealable reaction tube with a Teflon-coated cap equipped with a magnetic stir bar was charged with N-substituted indole (1, 0.50 mmol), PdACHTUNGRE(OAc)2 (0.0125 mmol), and DMAC (2.0 mL), then 1-aryltriazene (2, 0.60 mmol) and BF3·OEt2 (0.50 mmol) were added by syringe. The reaction mixture was stirred at 80 8C for 12 h. After the reaction was completed, it was cooled to room temperature, quenched with water, and extracted with ethyl acetate. The organic phase was dried over MgSO4, filtered, and concentrated under reduced pressure to yield the crude product,
mediate D. Finally, a reductive elimination from intermediate D produces the final coupling product 3 and Pd0 species, thus finishing the catalytic cycle. However, we cannot rule out the electrophilic substitution of the indole ring at the C3-position followed by a C3!C2 migration.[3a, 4d]
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which was further purified by flash chromatography on silica gel with ethyl acetate/petroleum ether (50:1!20:1) to provide the corresponding product (3).
(t, J = 7.3 Hz, 1 H), 7.04 (d, J = 8.2 Hz, 2 H), 6.55 (s, 1 H), 3.91 (s, 3 H), 3.76 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 159.5, 141.4, 138.1, 130.6, 128.0, 125.3, 121.4, 120.2, 119.7, 113.9, 109.5, 101.0, 55.3, 31.0 ppm.
1-Methyl-(p-tolyl)-1H-indole (3 a)[4b]
2-(4-Ethoxyphenyl)-1-methyl-1H-indole (3 j) Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.66 (d, J = 7.8 Hz, 1 H), 7.46 (d, J = 8.5 Hz, 2 H), 7.38 (d, J = 8.2 Hz, 1 H), 7.29–7.25 (m, 1 H), 7.17 (t, J = 7.4 Hz, 1 H), 7.02 (d, J = 8.5 Hz, 2 H), 6.54 (s, 1 H), 4.13 (q, J = 6.9 Hz, 2 H), 3.76 (s, 3 H), 1.49 ppm (t, J = 6.9 Hz, 3 H); 13C NMR (100 MHz, CDCl3): d = 158.8, 141.5, 138.1, 130.6, 128.0, 125.1, 121.3, 120.2, 119.7, 114.5, 109.5, 100.9, 63.5, 31.0, 14.8 ppm; HRMS (ESI): m/z calcd for C17H18NO: 252.1388 [M+H] + ; found: 252.1388.
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Colorless solid; H NMR (400 MHz, CDCl3): d = 7.80 (d, J = 7.6 Hz, 1 H), 7.56 (d, J = 7.8 Hz, 2 H), 7.50 (d, J = 8.1 Hz, 1 H), 7.43–7.39 (m, 3 H), 7.32 (t, J = 7.2 Hz, 1 H), 6.71 (s, 1 H), 3.85 (s, 3 H), 2.58 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 141.6, 138.2, 137.6, 129.9, 129.2, 129.1, 127.9, 121.4, 120.3, 119.7, 109.5, 101.3, 34.0, 21.2 ppm. 1-Methyl-2-phenyl-1H-indole (3 b)[4b] Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.70–7.68 (m, 1 H), 7.56–7.50 (m, 4 H), 7.45–7.40 (m, 2 H), 7.31–7.29 (m, 1 H), 7.20–7.18 (m, 1 H), 6.62–6.60 (m, 1 H), 3.79 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 141.6, 138.3, 132.8, 129.4, 128.5, 127.9, 127.8, 121.6, 120.5, 119.8, 109.6, 101.6, 31.1 ppm.
2-(4-Fluorophenyl)-1-methyl-1H-indole (3 k)[4b] Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.68 (d, J = 6.8 Hz, 1 H), 7.53–7.49 (m, 2 H), 7.40 (d, J = 8.0 Hz, 1 H), 7.30–7.29 (m, 1 H), 7.22–7.18 (m, 3 H), 6.58 (s, 1 H), 3.76 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 162.6 (d, J = 246.28 Hz), 140.4, 138.2, 131.0 (d, J = 8.1 Hz), 128.9 (d, J = 3.4 Hz), 127.8, 121.7, 120.4, 119.9, 115.5 (d, J = 21.4 Hz), 109.6, 101.7, 31.0 ppm.
1-Methyl-2-(m-tolyl)-1H-indole (3 c)[4b] Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.67 (d, J = 7.8 Hz, 1 H), 7.41–7.33 (m, 4 H), 7.30–7.24 (m, 2 H), 7.17 (t, J = 7.4 Hz, 1 H), 6.58 (s, 1 H), 3.78 (s, 3 H), 2.47 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 141.7, 138.3, 138.1, 132.7, 130.1, 128.6, 128.3, 128.0, 126.4, 121.5, 120.4, 119.8, 109.5, 101.5, 31.1, 21.5 ppm.
2-(4-Chlorophenyl)-1-methyl-1H-indole (3 l)[4b] Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.68 (d, J = 7.8 Hz, 1 H), 7.49–7.45 (m, 4 H), 7.40 (d, J = 8.2 Hz, 1 H), 7.30 (t, J = 7.6 Hz, 1 H), 7.20 (t, J = 7.2 Hz, 1 H), 6.59 (s, 1 H), 3.76 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 140.2, 138.4, 133.9, 131.3, 130.5, 128.7, 127.8, 121.9, 120.5, 120.0, 109.6, 102.0, 31.1 ppm.
1-Methyl-2-(o-tolyl)-1H-indole (3 d)[4b] Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.69 (d, J = 7.8 Hz, 1 H), 7.41–7.37 (m, 3 H), 7.35–7.29 (m, 3 H), 7.19 (t, J = 7.4 Hz, 1 H), 6.48 (s, 1 H), 3.55 (s, 3 H), 2.45 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 140.5, 138.0, 137.3, 132.5, 131.1, 130.0, 128.6, 128.0, 125.5, 121.2, 120.3, 119.6, 109.4, 101.5, 30.3, 20.0 ppm.
1,5-Dimethyl-2-(p-tolyl)-1H-indole (3 m) Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.50–7.47 (m, 3 H), 7.36–7.31 (m, 3 H), 7.15 (d, J = 8.2 Hz, 1 H), 3.54 (s, 1 H), 3.78 (s, 3 H), 2.56 (s, 3 H), 2.50 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 141.6, 137.6, 136.7, 130.0, 129.2, 129.1, 128.9, 128.2, 123.0, 120.0, 109.2, 100.7, 31.1, 21.4, 21.2 ppm; HRMS (ESI): m/z calcd for C17H18N: 236.1439 [M+H] + ; found: 236.1435.
2-(4-Ethylphenyl)-1-methyl-1H-indole (3 e)[15] Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.76 (d, J = 7.4 Hz, 1 H), 7.55 (d, J = 6.4 Hz, 2 H), 7.46 (d, J = 8.0 Hz, 1 H), 7.42–7.35 (m, 3 H), 7.29– 7.25 (m, 1 H), 6.67 (s, 1 H), 3.84 (s, 3 H), 2.84 (q, J = 7.4 Hz, 2 H), 1.43– 1.40 ppm (m, 3 H); 13C NMR (100 MHz, CDCl3): d = 144.0, 141.6, 138.2, 130.1, 129.3, 128.0, 127.9, 121.5, 120.3, 119.7, 109.5, 101.3, 31.1, 28.6, 15.5 ppm.
1,7-Dimethyl-2-(p-tolyl)-1H-indole (3 n)[9b] Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.50 (d, J = 7.7 Hz, 1 H), 7.40 (d, J = 7.8 Hz, 2 H), 7.30 (d, J = 7.8 Hz, 2 H), 7.02 (t, J = 7.4 Hz, 1 H), 6.95 (d, J = 6.8 Hz, 1 H), 6.51 (s, 1 H), 3.95 (s, 3 H), 2.84 (s, 3 H), 2.45 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 142.8, 137.7, 137.5, 130.1, 129.5, 129.1, 128.9, 124.5, 121.4, 120.0, 118.5, 102.1, 34.4, 21.3, 20.2 ppm.
2-(4-Isopropylphenyl)-1-methyl-1H-indole (3 f) Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.69 (d, J = 7.8 Hz, 1 H), 7.50 (d, J = 8.0 Hz, 2 H), 7.42–7.37 (m, 3 H), 7.30 (t, J = 7.6 Hz, 1 H), 7.20 (t, J = 7.4 Hz, 1 H), 6.60 (s, 1 H), 3.80 (s, 3 H), 3.09–2.98 (m, 1 H), 1.37 ppm (d, J = 6.9 Hz, 6 H); 13C NMR (100 MHz, CDCl3): d = 148.6, 141.7, 138.3, 130.3, 129.3, 128.0, 126.5, 121.5, 120.3, 119.7, 109.5, 101.3, 33.9, 31.1, 23.9 ppm; HRMS (ESI): m/z calcd for C18H20N: 250.1596 [M+H] + ; found: 250.1593.
5-Methoxy-1-methyl-2-(p-tolyl)-1H-indole (3 o)[9b] Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.44 (d, J = 7.8 Hz, 2 H), 7.32–7.27 (m, 3 H), 7.15 (s, 1 H), 6.95 (d, J = 8.8 Hz, 1 H), 6.51 (s, 1 H), 3.91 (s, 3 H), 3.75 (s, 3 H), 2.47 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 154.3, 142.2, 137.6, 133.7, 130.0,129.2, 129.1, 128.2, 111.6, 110.2, 102.1, 100.9, 55.9, 31.1, 21.2 ppm.
2-(3,4-Dimethylphenyl)-1-methyl-1H-indole (3 g)
5-Methoxy-1-methyl-2-phenyl-1H-indole (3 p)[4b]
Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.72 (d, J = 7.8 Hz, 1 H), 7.43 (d, J = 8.2 Hz, 1 H), 7.39 (s, 1 H), 7.34–7.30 (m, 3 H), 7.23 (t, J = 7.4 Hz, 1 H), 6.62 (s, 1 H), 3.81 (s, 3 H), 2.42 ppm (s, 6 H); 13C NMR (100 MHz, CDCl3): d = 141.7, 138.2, 136.7, 136.4, 130.6, 130.3, 129.7, 128.0, 126.7, 121.4, 120.3, 119.7, 109.5, 101.2, 31.0, 19.8, 19.5 ppm; HRMS (ESI): m/z calcd for C17H18N [M+H] + : 236.1439; found: 236.1436.
Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.57–7.50 (m, 4 H), 7.46–7.43 (m, 1 H), 7.31 (d, J = 8.8 Hz, 1 H), 7.17 (d, J = 1.9 Hz, 1 H), 6.99– 6.96 (m, 1 H), 6.55 (s, 1 H), 3.92 (s, 3 H), 3.76 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 154.34, 142.08, 133.78, 132.86, 129.23, 128.43, 128.22, 127.74, 111.86, 110.29, 102.17, 101.26, 55.88, 31.22 ppm. 5-Fluoro-1-methyl-2-(p-tolyl)-1H-indole (3 q)
2-(3,5-Dimethylphenyl)-1-methyl-1H-indole (3 h)[4b]
Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.42 (d, J = 7.9 Hz, 2 H), 7.32–7.27 (m, 4 H), 7.03–6.98 (m, 1 H), 6.51 (s, 1 H), 3.74 (s, 3 H), 2.46 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 158.1 (d, J = 232.66 Hz), 143.2, 138.0, 134.9, 129.6, 129.2 (d, J = 3.87 Hz), 128.1 (d, J = 10.09 Hz), 100.1 (d, J = 9.71 Hz), 109.8, 109.5, 105.1 (d, J = 23.29 Hz), 101.2 (d, J = 4.61 Hz), 31.3, 21.3 ppm; HRMS (ESI): m/z calcd for C16H15FN: 236.1439 [M+H] + ; found: 236.1435.
Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.73 (d, J = 7.8 Hz, 1 H), 7.44 (d, J = 8.2 Hz, 1 H), 7.34 (t, J = 7.3 Hz, 1 H), 7.27–7.23 (m, 3 H), 7.14 (s, 1 H), 6.64 (s, 1 H), 3.82 (s, 3 H), 2.49 ppm (s, 6 H); 13C NMR (100 MHz, CDCl3): d = 141.8, 138.3, 138.0, 132.7, 129.5, 128.0, 127.2, 121.4, 120.4, 119.7, 109.5, 101.4, 31.1, 21.3 ppm. 2-(4-Methoxyphenyl)-1-methyl-1H-indole (3 i)[4b] Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.67 (d, J = 7.7 Hz, 1 H), 7.48 (d, J = 8.2 Hz, 2 H), 7.39 (d, J = 8.1 Hz, 1 H), 7.30–7.26 (m, 1 H), 7.18
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6-Fluoro-1-methyl-2-(p-tolyl)-1H-indole (3 r)[9b]
1,3-Dimethyl-2-(p-tolyl)-1H-indole (3 z)[9b]
Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.60–7.54 (m, 1 H), 7.44 (d, J = 7.6 Hz, 2 H), 7.33 (d, J = 7.6 Hz, 2 H), 7.08 (d, J = 9.9 Hz, 1 H), 6.96 (t, J = 9.1 Hz, 1 H), 6.56 (s, 1 H), 3.73 (s, 3 H), 2.49 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 159.6 (d, J = 235.85 Hz), 142.1 (d, J = 3.77 Hz), 138.3 (d, J = 15.49 Hz), 137.8, 129.6, 129.2, 129.1, 124.3, 121.0 (d, J = 9.94 Hz), 108.4 (d, J = 24.23 Hz), 101.2, 96.0 (d, J = 26.02 Hz), 31.2, 21.2 ppm.
Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.71 (d, J = 7.8 Hz, 1 H), 7.43–7.39 (m, 5 H), 7.35 (t, J = 7.5 Hz, 1 H), 7.28–7.24 (m, 1 H), 3.69 (s, 3 H), 2.54 (s, 3 H), 2.39 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 137.7, 137.5, 137.1, 130.5, 129.1, 129.0, 128.4, 121.5, 119.0, 118.7, 109.1, 108.2, 30.8, 21.3, 9.5 ppm. 1-Ethyl-3-methyl-2-(p-tolyl)-1H-indole (3 aa) Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.67 (d, J = 7.8 Hz, 1 H), 7.43 (d, J = 8.1 Hz, 1 H), 7.36 (s, 4 H), 7.31 (t, J = 7.8 Hz, 1 H), 7.22 (t, J = 7.4 Hz, 1 H), 4.14 (q, J = 7.1 Hz, 2 H), 2.51 (s, 3 H), 2.32 (s, 3 H), 1.28 ppm (t, J = 7.1 Hz, 3 H); 13C NMR (100 MHz, CDCl3): d = 137.6, 137.2, 135.9, 130.4, 129.4, 129.1, 128.7, 121.4, 118.9, 118.8, 109.4, 108.5, 38.6, 21.3, 15.3, 9.2 ppm; HRMS (ESI): m/z calcd for C18H20N: 250.1596 [M+H] + ; found: 250.1598.
5-Chloro-1-methyl-2-(p-tolyl)-1H-indole (3 s) Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.60 (s, 1 H), 7.41 (d, J = 7.8 Hz, 2 H), 7.32–7.29 (m, 3 H), 7.20 (d, J = 8.6 Hz, 1 H), 6.49 (s, 1 H), 3.74 (s, 3 H), 2.45 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 142.9, 138.1, 136.6, 129.4, 129.3, 129.2, 128.9, 125.4, 121.6, 119.6, 110.5, 100.8, 31.2, 21.3 ppm; HRMS (ESI): m/z calcd for C16H15ClN: 256.0893 [M+H] + ; found: 256.0891.
1-Butyl-3-methyl-2-(p-tolyl)-1H-indole (3 ab)
5-Bromo-1-methyl-2-(p-tolyl)-1H-indole (3 t)[9b]
Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.65 (d, J = 7.8 Hz, 1 H), 7.41 (d, J = 8.1 Hz, 1 H), 7.34 (s, 4 H), 7.30–7.27 (m, 1 H), 7.20 (t, J = 7.4 Hz, 1 H), 4.08 (t, J = 7.4 Hz, 2 H), 2.50 (s, 3 H), 2.30 (s, 3 H), 1.68–1.61 (m, 2 H), 1.25–1.15 (m, 2 H), 0.83 ppm (t, J = 7.3 Hz, 3 H); 13C NMR (100 MHz, CDCl3): d = 137.5, 137.5, 136.2, 130.4, 129.4, 129.0, 128.5, 121.3, 118.8, 118.7, 109.6, 108.4, 43.6, 32.1, 21.3, 20.0, 13.7, 9.3 ppm; HRMS (ESI): m/z calcd for C20H24N: 278.1909 [M+H] + ; found: 278.1910.
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Colorless solid; H NMR (400 MHz, CDCl3): d = 7.77–7.76 (m, 1 H), 7.41 (d, J = 7.9 Hz, 2 H), 7.34–7.30 (m, 3 H), 7.23 (d, J = 8.7 Hz, 1 H), 6.49 (s, 1 H), 3.73 (s, 3 H), 2.46 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 142.8, 138.0, 136.9, 129.6, 129.3, 129.3, 129.2, 124.2, 122.7, 112.9, 110.9, 100.7, 31.2, 21.3 ppm. Methyl 2-(4-methoxyphenyl)-1-methyl-1H-indole-4-carboxylate (3 u) Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.55 (d, J = 7.2 Hz, 1 H), 7.49 (d, J = 8.2 Hz, 1 H), 7.30–7.25 (m, 3 H), 7.11 (s, 1 H), 6.94 (d, J = 8.2 Hz, 2 H), 3.83 (s, 6 H), 3.26 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 169.4, 157.9, 137.7, 129.45, 129.40, 129.3, 124.7, 123.6, 121.8, 121.0, 117.0, 113.5, 112.8, 55.3, 51.3, 32.9 ppm; HRMS (ESI): m/z calcd for C18H18NO3 : 296.1287 [M+H] + ; found: 296.1284.
Acknowledgements This work was financially supported by the National Science Foundation of China (grant nos. 21372095, 21172092).
1-Ethyl-2-(p-tolyl)-1H-indole (3 v)[9b] Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.68 (d, J = 7.8 Hz, 1 H), 7.45–7.43 (m, 3 H), 7.32 (d, J = 7.8 Hz, 2 H), 7.29–7.25 (m, 1 H), 7.18 (t, J = 7.4 Hz, 1 H), 6.55 (s, 1 H), 4.23 (q, J = 7.2 Hz, 2 H), 2.47 (s, 3 H), 1.36 ppm (t, J = 7.2 Hz, 3 H); 13C NMR (100 MHz, CDCl3): d = 141.1, 137.8, 137.0, 130.2, 129.2, 129.1, 128.3, 121.3, 120.5, 119.7, 109.8, 101.7, 38.7, 21.3, 15.4 ppm.
[1] a) R. H. Thomson, The Chemistry of Natural Products, Blackie, Son, Glasgow, 1985; b) K. G. B. Torssell, Natural Product Chemistry, Wiley, Chichester, 1983; c) K. Yamamura, S. Ono, H. Ogoshi, H. Masuda, Y. Kuroda, Synlett 1989, 18 – 19; d) I. J. Ninomiya, Nat. Prod. 1992, 55, 541 – 546; e) R. J. Sundberg, Indoles, Academic Press, San Diego, CA, 1996; f) J. Roncali, Chem. Rev. 1992, 92, 711 – 738; g) N. K. Garg, R. Sarpong, B. M. Stolz, J. Am. Chem. Soc. 2002, 124, 13179 – 13184; h) S. Cacchi, G. Fabrizi, Chem. Rev. 2005, 105, 2873 – 2920; i) M. Somei, F. Yamada, Nat. Prod. Rep. 2005, 22, 73 – 103. [2] a) S. S. Labadie, E. Teng, J. Org. Chem. 1994, 59, 4250 – 4254; b) E. Vedejs, D. A. Barda, Org. Lett. 2000, 2, 1033 – 1035; c) B. Chauder, A. Larkin, V. Snieckus, Org. Lett. 2002, 4, 815 – 817; d) X. Cai, V. Snieckus, Org. Lett. 2004, 6, 2293 – 2295; e) I. Bennacef, C. N. Haile, A. Schmidt, A. O. Koren, J. P. Seibyl, J. K. Staley, F. Bois, R. M. Baldwin, G. Tamagnan, Bioorg. Med. Chem. 2006, 14, 7582 – 7591; f) R. Dandu, M. Tao, K. A. Josef, E. R. Bacon, R. L. Hudkins, J. Heterocycl. Chem. 2007, 44, 437 – 440; g) Y. B. Liu, G. W. Gribble, Tetrahedron Lett. 2000, 41, 8717 – 8721; h) C. A. Merlic, Y. You, D. M. McInnes, A. L. Zechman, M. M. Miller, Q. Deng, Tetrahedron 2001, 57, 5199 – 5212; i) C. G. Hartung, A. Fecher, B. Chapell, V. Snieckus, Org. Lett. 2003, 5, 1899 – 1902; j) J. Joucla, L. Djakovitch, Adv. Synth. Catal. 2009, 351, 673 – 714. [3] a) B. S. Lane, M. A. Brown, D. Sames, J. Am. Chem. Soc. 2005, 127, 8050 – 8057; b) E. T. Nadres, A. Lazareva, O. Daugulis, J. Org. Chem. 2011, 76, 471 – 483; c) C. Bressy, D. Alberico, M. Lautens, J. Am. Chem. Soc. 2005, 127, 13148 – 13149; d) B. S. Lane, D. Sames, Org. Lett. 2004, 6, 2897 – 2990; e) X. Wang, B. S. Lane, D. Sames, J. Am. Chem. Soc. 2005, 127, 4996 – 4997; f) F. Bellina, S. Cauteruccio, R. Rossi, Eur. J. Org. Chem. 2006, 1379 – 1382; g) B. B. Tour, B. S. Lane, D. Sames, Org. Lett. 2006, 8, 1979 – 1982; h) X. Wang, D. V. Gribkov, D. Sames, J. Org. Chem. 2007, 72, 1476 – 1479; i) Z. Zhang, Z. Hu, Z. Yu, P. Lei, H. Chi, Y. Wang, R. He, Tetrahedron Lett. 2007, 48, 2415 – 2419; j) F. Bellina, C. Calandri, S. Cauteruccio, R.
1-Propyl-2-(p-tolyl)-1H-indole (3 w) Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.70 (d, J = 7.8 Hz, 1 H), 7.46–7.44 (m, 3 H), 7.35–7.29 (m, 3 H), 7.20 (t, J = 7.3 Hz, 1 H), 6.57 (s, 1 H), 4.17 (t, J = 7.8 Hz, 2 H), 2.50 (s, 3 H), 1.85–1.75 (m, 2 H), 0.85 ppm (t, J = 7.3 Hz, 3 H); 13C NMR (100 MHz, CDCl3): d = 141.6, 137.69, 137.3, 130.4, 129.3, 129.1,128.2, 121.3, 120.4, 119.6, 110.0, 101.7, 45.5, 23.3, 21.3, 11.3 ppm; HRMS (ESI): m/z calcd for C18H20N: 250.1596 [M+H] + ; found: 250.1592. 1-Butyl-2-(p-tolyl)-1H-indole (3 x) Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.73 (d, J = 7.7 Hz, 1 H), 7.49–7.46 (m, 3 H), 7.37–7.30 (m, 3 H), 7.23 (t, J = 7.3 Hz, 1 H), 6.59 (s, 1 H), 4.23 (t, J = 7.4 Hz, 2 H), 2.52 (s, 3 H), 1.82–1.74 (m, 2 H), 1.33–1.24 (m, 2 H), 0.91 ppm (t, J = 7.4 Hz, 3 H); 13C NMR (100 MHz, CDCl3): d = 141.4, 137.7, 137.3, 130.3, 129.3, 129.1, 128.2, 121.2, 120.4, 119.6, 109.9, 101.7, 43.7, 32.1, 21.3, 20.0, 13.6 ppm; HRMS (ESI): m/z calcd for C19H22N: 264.1752 [M+H] + ; found: 264.1749. 1-Benzyl-2-(p-tolyl)-1H-indole (3 y) Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.52 (d, J = 4.8 Hz, 1 H), 7.43 (d, J = 7.6 Hz, 2 H), 7.38–7.32 (m, 3 H), 7.29–7.24 (m, 5 H), 7.13 (d, J = 7.1 Hz, 2 H), 6.73 (s, 1 H), 5.44 (s, 2 H), 2.47 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 141.9, 138.3, 137.9, 137.9, 129.7, 129.3, 129.1, 128.7, 128.3, 127.1, 125.9, 121.7, 120.4, 120.1, 110.5, 101.9, 47.6, 21.2 ppm; HRMS (ESI): m/z calcd for C22H20N: 298.1596 [M+H] + ; found: 298.1598.
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[5]
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Rossi, Tetrahedron 2007, 63, 1970 – 1980; k) F. Bellina, F. Benelli, R. Rossi, J. Org. Chem. 2008, 73, 5529 – 5535; l) N. Lebrasseur, I. Larrosa, J. Am. Chem. Soc. 2008, 130, 2926 – 2927; m) N. S. Nandurkar, M. J. Bhanushali, M. D. Bhor, B. M. Bhanage, Tetrahedron Lett. 2008, 49, 1045 – 1048; n) G. Cusati, L. Djakovitch, Tetrahedron Lett. 2008, 49, 2499 – 2502; o) J. Roger, H. Doucet, Adv. Synth. Catal. 2009, 351, 1977 – 1990; p) B. Ligault, I. Petrov, S. I. Gorelsky, K. Fagnou, J. Org. Chem. 2010, 75, 1047 – 1060; q) F. Shibahara, E. Yamaguchi, T. Murai, Chem. Commun. 2010, 46, 2471 – 2473; r) L. Wang, W. B. Yi, C. Cai, Chem. Commun. 2011, 47, 806 – 808; s) S. Islam, I. Larrosa, Chem. Eur. J. 2013, 19, 15093 – 15096; t) H. Dong, C. Limberakis, S. Liras, D. Price, K. James, Chem. Commun. 2012, 48, 11644 – 11646; u) G.-P. Lu, C. Cai, Synlett 2012, 2992 – 2996; v) L. Joucla, N. Batail, L. Djakovitch, Adv. Synth. Catal. 2010, 352, 2929 – 2936; w) Y. Akita, A. Inoue, K. Yamamoto, A. Ohta, T. Kurihara, M. Shimizu, Heterocycles 1985, 23, 2327 – 2333; x) A. F. P. Biajoli, E. T. Penha, C. R. D. Correia, RSC Adv. 2012, 2, 11930 – 11935. a) S. Kirchberg, R. Frçhlich, A. S. Studer, Angew. Chem. Int. Ed. 2009, 48, 4235 – 4238; Angew. Chem. 2009, 121, 4299 – 4302; b) S.-D. Yang, C.-L. Sun, Z. Fang, B.-J. Li, Y. Li, Z.-J. Shi, Angew. Chem. Int. Ed. 2008, 47, 1473 – 1476; Angew. Chem. 2008, 120, 1495 – 1498; c) Y. Huang, T. Ma, P. Huang, D. Wu, Z. Lin, R. Cao, ChemCatChem 2013, 5, 1877 – 1883; d) J. Zhao, Y. Zhang, K. Cheng, J. Org. Chem. 2008, 73, 7428 – 7431. a) N. R. Deprez, D. Kalyani, A. Krause, M. S. Sanford, J. Am. Chem. Soc. 2006, 128, 4972 – 4973; b) R. J. Phipps, N. P. Grimster, M. J. Gaunt, J. Am. Chem. Soc. 2008, 130, 8172 – 8174. Z.-J. Liang, B.-B. Yao, Y.-H. Zhang, Org. Lett. 2010, 12, 3185 – 3187. a) J. Cornella, P. F. Lu, I. Larrosa, Org. Lett. 2009, 11, 5506 – 5509; b) J. Zhou, P. Hu, M. Zhang, S. Huang, M. Wang, W.-P. Su, Chem. Eur. J. 2010, 16, 5876 – 5881. a) D. R. Stuart, K. Fagnou, Science 2007, 316, 1172 – 1175; b) D. R. Stuart, E. Villemure, K. Fagnou, J. Am. Chem. Soc. 2007, 129, 12072 – 12073; c) S. Potavathri, A. S. Dumas, T. A. Dwight, G. R. Naumiec, J. M. Hammann, B. DeBoef, Tetrahedron Lett. 2008, 49,
Chem. Asian J. 2014, 00, 0 – 0
[9]
[10] [11]
[12]
[13] [14]
[15]
6
Lei Wang et al.
4050 – 4053; d) Z. Liang, J. Zhao, Y. Zhang, J. Org. Chem. 2010, 75, 170 – 177; e) A. Garca-Rubia, B. Urones, R. Gmez Arrays, J. C. Carretero, Chem. Eur. J. 2010, 16, 9676 – 9685; f) D. G. Pintori, M. F. Greaney, J. Am. Chem. Soc. 2011, 133, 1209 – 1211; g) S. Potavathri, K. C. Pereira, S. I. Gorelsky, A. Pike, A. P. LeBris, B. DeBoef, J. Am. Chem. Soc. 2010, 132, 14676 – 14681; h) T. Itahara, T. Sakakibara, Synthesis 1978, 607 – 608; i) T. Itahara, Synthesis 1979, 151 – 152; j) T. A. Dwight, N. R. Rue, D. Charyk, R. Josselyn, B. DeBoef, Org. Lett. 2007, 9, 3137 – 3139. a) T. Miao, P. Li, G.-W. Wang, L. Wang, Chem. Asian J. 2013, 8, 3185 – 3190; b) M. Wu, J. Luo, F. Xiao, S. Zhang, G.-J. Deng, H.-A. Luo, Adv. Synth. Catal. 2012, 354, 335 – 340. M. Dçbele, S. Vanderheiden, N. Jung, S. Brse, Angew. Chem. Int. Ed. 2010, 49, 5986 – 5988; Angew. Chem. 2010, 122, 6122 – 6125. a) D. B. Kimball, M. M. Haley, Angew. Chem. Int. Ed. 2002, 41, 3338 – 3351; Angew. Chem. 2002, 114, 3484 – 3498; b) C. Zhu, M, Yamane, Org. Lett. 2012, 14, 4560 – 4563; c) A. Hafner, S. Brse, Adv. Synth. Catal. 2013, 355, 996 – 1000; d) C.-Y. Liu, P. Knochel, Org. Lett. 2005, 7, 2543 – 2546; e) C.-Y. Liu, P. Knochel, J. Org. Chem. 2007, 72, 7106 – 7115; f) J. Zhou, W. Yang, B. Wang, H. Ren, Angew. Chem. Int. Ed. 2012, 51, 12293 – 12297; Angew. Chem. 2012, 124, 12459 – 12463. a) S. Bhattacharya, S. Majee, R. Mukherjee, S. Sengupta, Synth. Commun. 1995, 25, 651 – 657; b) S. Sengupta, S. K. Sadhukkan, Tetrahedron Lett. 1998, 39, 715 – 718; c) S. Sengupta, S. K. Sadhukkan, Org. Synth. 2002, 79, 52 – 56. S. Brse, M. Schroen, Angew. Chem. Int. Ed. 1999, 38, 1071 – 1073; Angew. Chem. 1999, 111, 1139 – 1142. a) T. Saeki, E.-C. Son, K. Tamao, Org. Lett. 2004, 6, 617 – 619; b) T. Saeki, T. Matsunaga, E.-C. Son, K. Tamao, Adv. Synth. Catal. 2004, 346, 1689 – 1692. M. F. Ibad, D. S. Zinad, M. Hussain, A. Ali, A. Villinger, P. Langer, Tetrahedron 2013, 69, 7492 – 7504. Received: March 22, 2014 Published online: && &&, 0000
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FULL PAPER CH Functionalization Can Liu, Tao Miao, Lei Zhang, Pinhua Li, Yicheng Zhang, &&&&—&&&& Lei Wang*
Seeing to C2: An efficient Pd-catalyzed C2 arylation of N-substituted indoles with 1-aryltriazenes for the synthesis of 2-arylindoles has been developed. In the presence of BF3·OEt2 and palladium(II) acetate,
N-substituted indoles reacted with 1aryltriazenes in N,N-dimethylacetamide to afford the corresponding aryl– indole-type products in good to excellent yields.
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Palladium-Catalyzed Direct C2 Arylation of N-Substituted Indoles with 1Aryltriazenes
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Palladium-Catalyzed Direct C2 Arylation of N-Substituted Indoles with 1Aryltriazenes Can Liu,[a] Tao Miao,[a] Lei Zhang,[a] Pinhua Li,[a] Yicheng Zhang,[a] and Lei Wang*[a, b] Abstract: A novel and efficient palladium-catalyzed C2 arylation of N-substituted indoles with 1-aryltriazenes for the synthesis of 2-arylindoles was developed. In the presence of BF3·OEt2 and palladium(II) acetate (PdACHTUNGRE(OAc)2), N-substituted indoles reacted with 1-aryltriazenes in N,N-dimethylacetamide (DMAC) to afford the corresponding aryl–indole-type products in good to excellent yields.
Introduction
a series of different functionalities after treatment with the appropriate reagents.[11] In addition, they also have been employed as electrophilic partners in transition-metal-catalyzed carbon–carbon cross-coupling reactions. For example, Sengupta et al. disclosed that aromatic triazenes were good coupling partners in Heck-type reactions.[12] Subsequently, Brse et al. extended their methodology to solid-phase organic synthesis.[13] Tamao et al. developed a palladium-catalyzed cross-coupling reaction of 1-aryltriazenes with arylboronic acids and aryltrifluorosilanes under mild reaction conditions.[14] However, the application of 1-aryltriazenes in the reaction of direct CH arylation of heteroaromatics is still unexplored. Herein, we wish to report a new and practical method for the synthesis of 2-arylindoles through palladiumcatalyzed C2 arylation of N-substituted indoles with 1-aryltriazenes in the presence of boron trifluoride, thereby providing the desired aryl–indole-type products in good to excellent yields (Scheme 1).
The arylation of indoles has been and continues to be a focus of research efforts for synthetic organic chemists because the arylated indoles are important building blocks in natural products, pharmaceuticals, and synthetic functional materials.[1] Over the past several years, the transitionmetal-catalyzed direct CH arylation of indoles with activated arenes has been successfully achieved, which provides an efficient approach for the straightforward synthesis of aryl– indole units without the need for prior functionalization of indoles (i.e., halogenation or stoichiometric metalation).[2] A variety of arylating agents, including organic halides,[3] organoboranes,[4] hypervalent iodines,[5] arylsiloxanes,[6] aromatic carboxylic acids,[7] and arenes[8] have been explored in the direct arylation reaction of indoles. More recently, we and others reported that arylsulfinic acids (salts) were good coupling partners in the direct C-arylation of indoles in the presence of palladium catalyst.[9] Despite remarkable advances in this type of transformation, the establishment of new and efficient synthetic methods for the preparation of aryl– indoles with high selectivity at the 2-position (not at the 3position) from readily available and simple aryl sources is highly desirable from both scientific and practical standpoints. Aromatic triazenes, which are very useful and versatile intermediates in organic synthesis, can be readily prepared from the corresponding arylamines by means of a simple one-step procedure.[10] They also can be converted into
Scheme 1. Pd-catalyzed C2 arylation of indoles with 1-aryltriazenes.
Results and Discussion In our initial study, N-methylindole (1 a) and 1-(p-tolyl)triazene (2 a) were chosen as model substrates to survey the reaction parameters. It was found that the catalysts, additives, and solvents play a critical role in the model reaction. Boron trifluoride (BF3) is an efficient reagent to enhance the reactivity of aryltriazenes in palladium-catalyzed crosscoupling reactions.[14a] We also attempted this arylated reaction using boron trifluoride as an additive to promote the reaction. As shown in Table 1, when palladium(II) acetate (PdACHTUNGRE(OAc)2) was used as a catalyst with BF3·OEt2 as an addi-
[a] C. Liu, T. Miao, L. Zhang, Prof. P. Li, Y. Zhang, Prof. L. Wang Department of Chemistry, Huaibei Normal University Huaibei, Anhui 235000 (P.R. China) Fax: (+ 86) 561-3090518 E-mail: [email protected] [b] Prof. L. Wang State Key Laboratory of Organometallic Chemistry Shanghai Institute of Organic Chemistry Shanghai 200032 (P.R. China) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/asia.201402274.
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Keywords: arylation · crosscoupling · heterocycles · homogeneous catalysis · palladium
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ACHTUNGRE(PPh3)2Cl2]) gave inferior results (Table 1, entries 17–20). When the catalyst loading was reduced from 2.5 to 1.0 mol %, the reaction afforded the desired product in 48 % yield (Table 1, entry 21). However, N-methylindole (1 a) did not react with 1-(p-tolyl)triazene (2 a) in the absence of either the palladium catalyst or the Lewis acid additive. It was indicated that PdACHTUNGRE(OAc)2 and BF3·OEt2 were essential for the direct C2 arylation of N-substituted indoles with 1aryltriazenes (Table 1, entries 22 and 23). Although aryldiazonium salts, as a precursor of 1-aryltriazenes, have been widely used as aryl reagents in organic synthesis, only 30 % yield of 3 a was obtained when p-tolyldiazonium tetrafluoroborate was employed in the reaction with 1 a under standard reaction conditions (Table 1, entry 24). With the optimized reaction conditions (2.5 mol % of PdACHTUNGRE(OAc)2, BF3·OEt2 (1 equiv), DMAC, 80 8C, 12 h) in hand, this Pd-catalyzed direct C2 arylation of indole was then extended to a wide array of 1-aryltriazenes and various indoles to explore the scope and limitation of the reaction. As can be seen from Scheme 2, the reactions of N-methylindole (1 a) with a wide range of 1-aryltriazenes proceeded well and generated the desired products in good to excellent yields. 1-Aryltriazenes with electron-rich groups, including methyl, ethyl, isopropyl, methoxy, and ethoxy on the benzene rings reacted with 1 a efficiently and afforded the desired products 3 a–j in 81–95 % yields. In contrast, the electron-deficient 1-aryltriazenes presented relatively lower reactivity, and the corresponding arylated products 3 k and 3 l were obtained in 74 and 65 % yields, respectively. It is notable that the steric-hindrance effect was not clear when ortho-substituted 1-aryltriazene was used as one of the substrates in the reaction (3 d, 82 % yield).[4b, 5a] Meanwhile, triazenes that bear cyclic side chains, such as five-membered pyrrolidine and six-membered piperidine, were also good substrates for this arylation reaction and generated the product 3 a in 87 and 82 % yields. The substrate scope with respect to indoles was also investigated. A series of functional groups, such as methyl, methoxy, fluoro, chloro, bromo, and ester were tolerated under the optimal reaction conditions, and the desired products 3 m–u were obtained in 57–85 % yields. It should be noted that N-ethylindole, N-propylindole, N-butylindole, and Nbenzylindole also reacted with 1-aryltriazenes efficiently, and the corresponding products 3 v–y were obtained in 77– 87 % yields. Furthermore, some steric bulk indoles, such as 1,3-dimethylindole, 1-ethyl-3-methylindole, and 1-butyl-3methylindole were arylated with 2 a smoothly to generate 3 z, 3 aa, and 3 ab in 95, 89, and 87 % yields, respectively. Although the mechanism of this reaction has not been clear up to now, on the basis of previous literature[3a, l, 9, 14a] and the above observations, we propose a possible pathway as shown in Scheme 3. In the presence of BF3·OEt2, the formed triazene–BF3 complex A is followed by the generation of arenediazonium salt B.[11b] Then, oxidative addition of the ArN bond in an arenediazonium salt (B) with in situ generated Pd0 affords an arylpalladium cation C, which reacts with 1 a in the C2-position, thereby providing inter-
Table 1. Palladium-catalyzed direct C2 arylation of N-methylindole with 1-(p-tolyl)triazene under various conditions.[a]
Entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Pd catalyst
Additive
Solvent
PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2 [PdACHTUNGRE(PPh3)4] ACHTUNGRE[Pd2ACHTUNGRE(dba)3] PdCl2 [PdACHTUNGRE(CH3CN)2Cl2] [PdACHTUNGRE(PPh3)2Cl2] PdACHTUNGRE(OAc)2 – PdACHTUNGRE(OAc)2 PdACHTUNGRE(OAc)2
BF3·OEt2 BF3·OEt2 BF3·OEt2 BF3·OEt2 BF3·OEt2 BF3·OEt2 BF3·OEt2 BF3·OEt2 BF3·OEt2 BF3·OEt2 BF3·OEt2 BF3·OEt2 FeCl3 CuCl2 AlCl3 BF3·OEt2 BF3·OEt2 BF3·OEt2 BF3·OEt2 BF3·OEt2 BF3·OEt2 BF3·OEt2 – BF3·OEt2
DMF DMAC NMP DMSO CH3OH CH3CO2H CH3CN toluene dioxane THF CH2Cl2 DCE DMAC DMAC DMAC DMAC DMAC DMAC DMAC DMAC DMAC DMAC DMAC DMAC
Yield [%][b] 60 92 80 64 NR[c] NR 11 trace NR NR NR NR NR NR NR 73 60 50 47 27 48[d] NR NR 30[e]
[a] Reaction conditions: 1 a (0.50 mmol), 2 a (0.60 mmol), Pd catalyst (2.5 mol %), additive (0.50 mmol), solvent (2.0 mL), 80 8C, 12 h. [b] Isolated yield. [c] NR = no reaction. [d] 1.0 mol % PdACHTUNGRE(OAc)2 was used. [e] pTolyldiazonium tetrafluoroborate was used as substrate instead of 2 a.
tive and DMF as a solvent, the reaction of 1 a with 2 a generated the corresponding arylated product, 3 a, in 60 % yield (Table 1, entry 1). Much to our pleasure, 92 % isolated yield of 3 a was obtained when N,N-dimethylacetamide (DMAC) was used as solvent instead of DMF (Table 1, entry 2). Further screening of solvents revealed that DMAC was the best solvent, and other polar solvents, such as N-methyl-2-pyrrolidone (NMP) and DMSO were also effective and provided 3 a in good yields, but ethanol and acetic acid were harmful to this arylation (Table 1, entries 3–6). Several low-polar solvents including acetonitrile, toluene, dioxane, dichloroethane (DCE), dichloromethane, and tetrahydrofuran (THF) were also examined; all of them were improper solvents and the model reaction was almost prohibited (Table 1, entries 7–12). The effect of a Lewis acid was investigated on the model reaction by using FeCl3, CuCl2, and AlCl3 in place of BF3·OEt2, and the results showed that no desired product 3 a was obtained (Table 1, entries 13–15). Among the palladium species tested, [PdACHTUNGRE(PPh3)4] exhibited good activity, and 3 a was isolated in 73 % yield (Table 1, entry 16), whereas other palladium catalysts (i.e., [Pd2ACHTUNGRE(dba)3] (dba = dibenzylideneacetone), PdCl2, [PdACHTUNGRE(CH3CN)2Cl2], [Pd&
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Scheme 3. The proposed reaction mechanism.
Conclusion In summary, we have developed a palladium-catalyzed efficient method for the direct C2 arylation of indoles with 1-aryltriazenes in the presence of BF3·OEt2. To the best of our knowledge, this is the first CH arylation of indoles using 1aryltriazenes as the aryl source by means of a Pd-catalyzed cross-coupling process. This new arylation provides an alternative means of access to a broad spectrum of C2 arylated indoles in good to excellent yields. The investigation of a detailed reaction mechanism and 1-aryltriazenes as coupling species in other reactions is underway.
Experimental Section General All 1H and 13C NMR spectra were recorded with 400 MHz Bruker FTNMR spectrometers (400 or 100 MHz, respectively). All chemical shifts are given as d values [ppm] with reference to tetramethylsilane (TMS) as an internal standard. The chemicals and solvents were purchased from commercial suppliers either from Aldrich, USA or the Shanghai Chemical Company, China. Products were purified by flash chromatography on 100–200 mesh silica gels (SiO2). Typical procedure for synthetic aryltriazenes[11b] A solution of primary arylamine (4.0 mmol) in HCl (aqueous, 37 %, 2.0 mL) was cooled in an ice bath while a solution of NaNO2 (310 mg, 4.5 mmol) in cold water (8.0 mL) was added dropwise. The resulting solution of the diazonium salt was stirred at 0 8C for 30 min and then added to a solution of diethylamine (1.46 g, 20.0 mmol) and K2CO3 (6.91 g, 50.0 mmol) in acetonitrile/water (1:2, 20.0 mL) in one portion. The reaction mixture was allowed to warm to room temperature and stirred for 30 min. The aqueous phase was extracted with ethyl acetate (3 10 mL). The organic phase was washed twice with brine, dried with MgSO4, and concentrated under reduced pressure. The crude product was purified by flash column chromatography over silica gel to give the corresponding aryltriazene.
Scheme 2. Palladium-catalyzed direct C2 arylation of N-substituted indoles with 1-aryltriazenes.[a] Reaction conditions: a) 1 (0.50 mmol), 2 (0.60 mmol), PdACHTUNGRE(OAc)2 (2.5 mol %), BF3·OEt2 (0.50 mmol), DMAC (2.0 mL), 80 8C, 12 h. b) Yields of isolated products. c) 1-(Phenyldiazenyl)pyrrolidine was used instead of 2 a. d) 1-(Phenyldiazenyl)piperidine was used instead of 2 a.
Typical procedure for the C2 arylation of N-substituted indoles A 10 mL sealable reaction tube with a Teflon-coated cap equipped with a magnetic stir bar was charged with N-substituted indole (1, 0.50 mmol), PdACHTUNGRE(OAc)2 (0.0125 mmol), and DMAC (2.0 mL), then 1-aryltriazene (2, 0.60 mmol) and BF3·OEt2 (0.50 mmol) were added by syringe. The reaction mixture was stirred at 80 8C for 12 h. After the reaction was completed, it was cooled to room temperature, quenched with water, and extracted with ethyl acetate. The organic phase was dried over MgSO4, filtered, and concentrated under reduced pressure to yield the crude product,
mediate D. Finally, a reductive elimination from intermediate D produces the final coupling product 3 and Pd0 species, thus finishing the catalytic cycle. However, we cannot rule out the electrophilic substitution of the indole ring at the C3-position followed by a C3!C2 migration.[3a, 4d]
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which was further purified by flash chromatography on silica gel with ethyl acetate/petroleum ether (50:1!20:1) to provide the corresponding product (3).
(t, J = 7.3 Hz, 1 H), 7.04 (d, J = 8.2 Hz, 2 H), 6.55 (s, 1 H), 3.91 (s, 3 H), 3.76 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 159.5, 141.4, 138.1, 130.6, 128.0, 125.3, 121.4, 120.2, 119.7, 113.9, 109.5, 101.0, 55.3, 31.0 ppm.
1-Methyl-(p-tolyl)-1H-indole (3 a)[4b]
2-(4-Ethoxyphenyl)-1-methyl-1H-indole (3 j) Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.66 (d, J = 7.8 Hz, 1 H), 7.46 (d, J = 8.5 Hz, 2 H), 7.38 (d, J = 8.2 Hz, 1 H), 7.29–7.25 (m, 1 H), 7.17 (t, J = 7.4 Hz, 1 H), 7.02 (d, J = 8.5 Hz, 2 H), 6.54 (s, 1 H), 4.13 (q, J = 6.9 Hz, 2 H), 3.76 (s, 3 H), 1.49 ppm (t, J = 6.9 Hz, 3 H); 13C NMR (100 MHz, CDCl3): d = 158.8, 141.5, 138.1, 130.6, 128.0, 125.1, 121.3, 120.2, 119.7, 114.5, 109.5, 100.9, 63.5, 31.0, 14.8 ppm; HRMS (ESI): m/z calcd for C17H18NO: 252.1388 [M+H] + ; found: 252.1388.
1
Colorless solid; H NMR (400 MHz, CDCl3): d = 7.80 (d, J = 7.6 Hz, 1 H), 7.56 (d, J = 7.8 Hz, 2 H), 7.50 (d, J = 8.1 Hz, 1 H), 7.43–7.39 (m, 3 H), 7.32 (t, J = 7.2 Hz, 1 H), 6.71 (s, 1 H), 3.85 (s, 3 H), 2.58 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 141.6, 138.2, 137.6, 129.9, 129.2, 129.1, 127.9, 121.4, 120.3, 119.7, 109.5, 101.3, 34.0, 21.2 ppm. 1-Methyl-2-phenyl-1H-indole (3 b)[4b] Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.70–7.68 (m, 1 H), 7.56–7.50 (m, 4 H), 7.45–7.40 (m, 2 H), 7.31–7.29 (m, 1 H), 7.20–7.18 (m, 1 H), 6.62–6.60 (m, 1 H), 3.79 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 141.6, 138.3, 132.8, 129.4, 128.5, 127.9, 127.8, 121.6, 120.5, 119.8, 109.6, 101.6, 31.1 ppm.
2-(4-Fluorophenyl)-1-methyl-1H-indole (3 k)[4b] Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.68 (d, J = 6.8 Hz, 1 H), 7.53–7.49 (m, 2 H), 7.40 (d, J = 8.0 Hz, 1 H), 7.30–7.29 (m, 1 H), 7.22–7.18 (m, 3 H), 6.58 (s, 1 H), 3.76 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 162.6 (d, J = 246.28 Hz), 140.4, 138.2, 131.0 (d, J = 8.1 Hz), 128.9 (d, J = 3.4 Hz), 127.8, 121.7, 120.4, 119.9, 115.5 (d, J = 21.4 Hz), 109.6, 101.7, 31.0 ppm.
1-Methyl-2-(m-tolyl)-1H-indole (3 c)[4b] Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.67 (d, J = 7.8 Hz, 1 H), 7.41–7.33 (m, 4 H), 7.30–7.24 (m, 2 H), 7.17 (t, J = 7.4 Hz, 1 H), 6.58 (s, 1 H), 3.78 (s, 3 H), 2.47 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 141.7, 138.3, 138.1, 132.7, 130.1, 128.6, 128.3, 128.0, 126.4, 121.5, 120.4, 119.8, 109.5, 101.5, 31.1, 21.5 ppm.
2-(4-Chlorophenyl)-1-methyl-1H-indole (3 l)[4b] Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.68 (d, J = 7.8 Hz, 1 H), 7.49–7.45 (m, 4 H), 7.40 (d, J = 8.2 Hz, 1 H), 7.30 (t, J = 7.6 Hz, 1 H), 7.20 (t, J = 7.2 Hz, 1 H), 6.59 (s, 1 H), 3.76 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 140.2, 138.4, 133.9, 131.3, 130.5, 128.7, 127.8, 121.9, 120.5, 120.0, 109.6, 102.0, 31.1 ppm.
1-Methyl-2-(o-tolyl)-1H-indole (3 d)[4b] Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.69 (d, J = 7.8 Hz, 1 H), 7.41–7.37 (m, 3 H), 7.35–7.29 (m, 3 H), 7.19 (t, J = 7.4 Hz, 1 H), 6.48 (s, 1 H), 3.55 (s, 3 H), 2.45 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 140.5, 138.0, 137.3, 132.5, 131.1, 130.0, 128.6, 128.0, 125.5, 121.2, 120.3, 119.6, 109.4, 101.5, 30.3, 20.0 ppm.
1,5-Dimethyl-2-(p-tolyl)-1H-indole (3 m) Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.50–7.47 (m, 3 H), 7.36–7.31 (m, 3 H), 7.15 (d, J = 8.2 Hz, 1 H), 3.54 (s, 1 H), 3.78 (s, 3 H), 2.56 (s, 3 H), 2.50 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 141.6, 137.6, 136.7, 130.0, 129.2, 129.1, 128.9, 128.2, 123.0, 120.0, 109.2, 100.7, 31.1, 21.4, 21.2 ppm; HRMS (ESI): m/z calcd for C17H18N: 236.1439 [M+H] + ; found: 236.1435.
2-(4-Ethylphenyl)-1-methyl-1H-indole (3 e)[15] Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.76 (d, J = 7.4 Hz, 1 H), 7.55 (d, J = 6.4 Hz, 2 H), 7.46 (d, J = 8.0 Hz, 1 H), 7.42–7.35 (m, 3 H), 7.29– 7.25 (m, 1 H), 6.67 (s, 1 H), 3.84 (s, 3 H), 2.84 (q, J = 7.4 Hz, 2 H), 1.43– 1.40 ppm (m, 3 H); 13C NMR (100 MHz, CDCl3): d = 144.0, 141.6, 138.2, 130.1, 129.3, 128.0, 127.9, 121.5, 120.3, 119.7, 109.5, 101.3, 31.1, 28.6, 15.5 ppm.
1,7-Dimethyl-2-(p-tolyl)-1H-indole (3 n)[9b] Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.50 (d, J = 7.7 Hz, 1 H), 7.40 (d, J = 7.8 Hz, 2 H), 7.30 (d, J = 7.8 Hz, 2 H), 7.02 (t, J = 7.4 Hz, 1 H), 6.95 (d, J = 6.8 Hz, 1 H), 6.51 (s, 1 H), 3.95 (s, 3 H), 2.84 (s, 3 H), 2.45 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 142.8, 137.7, 137.5, 130.1, 129.5, 129.1, 128.9, 124.5, 121.4, 120.0, 118.5, 102.1, 34.4, 21.3, 20.2 ppm.
2-(4-Isopropylphenyl)-1-methyl-1H-indole (3 f) Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.69 (d, J = 7.8 Hz, 1 H), 7.50 (d, J = 8.0 Hz, 2 H), 7.42–7.37 (m, 3 H), 7.30 (t, J = 7.6 Hz, 1 H), 7.20 (t, J = 7.4 Hz, 1 H), 6.60 (s, 1 H), 3.80 (s, 3 H), 3.09–2.98 (m, 1 H), 1.37 ppm (d, J = 6.9 Hz, 6 H); 13C NMR (100 MHz, CDCl3): d = 148.6, 141.7, 138.3, 130.3, 129.3, 128.0, 126.5, 121.5, 120.3, 119.7, 109.5, 101.3, 33.9, 31.1, 23.9 ppm; HRMS (ESI): m/z calcd for C18H20N: 250.1596 [M+H] + ; found: 250.1593.
5-Methoxy-1-methyl-2-(p-tolyl)-1H-indole (3 o)[9b] Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.44 (d, J = 7.8 Hz, 2 H), 7.32–7.27 (m, 3 H), 7.15 (s, 1 H), 6.95 (d, J = 8.8 Hz, 1 H), 6.51 (s, 1 H), 3.91 (s, 3 H), 3.75 (s, 3 H), 2.47 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 154.3, 142.2, 137.6, 133.7, 130.0,129.2, 129.1, 128.2, 111.6, 110.2, 102.1, 100.9, 55.9, 31.1, 21.2 ppm.
2-(3,4-Dimethylphenyl)-1-methyl-1H-indole (3 g)
5-Methoxy-1-methyl-2-phenyl-1H-indole (3 p)[4b]
Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.72 (d, J = 7.8 Hz, 1 H), 7.43 (d, J = 8.2 Hz, 1 H), 7.39 (s, 1 H), 7.34–7.30 (m, 3 H), 7.23 (t, J = 7.4 Hz, 1 H), 6.62 (s, 1 H), 3.81 (s, 3 H), 2.42 ppm (s, 6 H); 13C NMR (100 MHz, CDCl3): d = 141.7, 138.2, 136.7, 136.4, 130.6, 130.3, 129.7, 128.0, 126.7, 121.4, 120.3, 119.7, 109.5, 101.2, 31.0, 19.8, 19.5 ppm; HRMS (ESI): m/z calcd for C17H18N [M+H] + : 236.1439; found: 236.1436.
Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.57–7.50 (m, 4 H), 7.46–7.43 (m, 1 H), 7.31 (d, J = 8.8 Hz, 1 H), 7.17 (d, J = 1.9 Hz, 1 H), 6.99– 6.96 (m, 1 H), 6.55 (s, 1 H), 3.92 (s, 3 H), 3.76 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 154.34, 142.08, 133.78, 132.86, 129.23, 128.43, 128.22, 127.74, 111.86, 110.29, 102.17, 101.26, 55.88, 31.22 ppm. 5-Fluoro-1-methyl-2-(p-tolyl)-1H-indole (3 q)
2-(3,5-Dimethylphenyl)-1-methyl-1H-indole (3 h)[4b]
Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.42 (d, J = 7.9 Hz, 2 H), 7.32–7.27 (m, 4 H), 7.03–6.98 (m, 1 H), 6.51 (s, 1 H), 3.74 (s, 3 H), 2.46 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 158.1 (d, J = 232.66 Hz), 143.2, 138.0, 134.9, 129.6, 129.2 (d, J = 3.87 Hz), 128.1 (d, J = 10.09 Hz), 100.1 (d, J = 9.71 Hz), 109.8, 109.5, 105.1 (d, J = 23.29 Hz), 101.2 (d, J = 4.61 Hz), 31.3, 21.3 ppm; HRMS (ESI): m/z calcd for C16H15FN: 236.1439 [M+H] + ; found: 236.1435.
Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.73 (d, J = 7.8 Hz, 1 H), 7.44 (d, J = 8.2 Hz, 1 H), 7.34 (t, J = 7.3 Hz, 1 H), 7.27–7.23 (m, 3 H), 7.14 (s, 1 H), 6.64 (s, 1 H), 3.82 (s, 3 H), 2.49 ppm (s, 6 H); 13C NMR (100 MHz, CDCl3): d = 141.8, 138.3, 138.0, 132.7, 129.5, 128.0, 127.2, 121.4, 120.4, 119.7, 109.5, 101.4, 31.1, 21.3 ppm. 2-(4-Methoxyphenyl)-1-methyl-1H-indole (3 i)[4b] Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.67 (d, J = 7.7 Hz, 1 H), 7.48 (d, J = 8.2 Hz, 2 H), 7.39 (d, J = 8.1 Hz, 1 H), 7.30–7.26 (m, 1 H), 7.18
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6-Fluoro-1-methyl-2-(p-tolyl)-1H-indole (3 r)[9b]
1,3-Dimethyl-2-(p-tolyl)-1H-indole (3 z)[9b]
Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.60–7.54 (m, 1 H), 7.44 (d, J = 7.6 Hz, 2 H), 7.33 (d, J = 7.6 Hz, 2 H), 7.08 (d, J = 9.9 Hz, 1 H), 6.96 (t, J = 9.1 Hz, 1 H), 6.56 (s, 1 H), 3.73 (s, 3 H), 2.49 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 159.6 (d, J = 235.85 Hz), 142.1 (d, J = 3.77 Hz), 138.3 (d, J = 15.49 Hz), 137.8, 129.6, 129.2, 129.1, 124.3, 121.0 (d, J = 9.94 Hz), 108.4 (d, J = 24.23 Hz), 101.2, 96.0 (d, J = 26.02 Hz), 31.2, 21.2 ppm.
Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.71 (d, J = 7.8 Hz, 1 H), 7.43–7.39 (m, 5 H), 7.35 (t, J = 7.5 Hz, 1 H), 7.28–7.24 (m, 1 H), 3.69 (s, 3 H), 2.54 (s, 3 H), 2.39 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 137.7, 137.5, 137.1, 130.5, 129.1, 129.0, 128.4, 121.5, 119.0, 118.7, 109.1, 108.2, 30.8, 21.3, 9.5 ppm. 1-Ethyl-3-methyl-2-(p-tolyl)-1H-indole (3 aa) Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.67 (d, J = 7.8 Hz, 1 H), 7.43 (d, J = 8.1 Hz, 1 H), 7.36 (s, 4 H), 7.31 (t, J = 7.8 Hz, 1 H), 7.22 (t, J = 7.4 Hz, 1 H), 4.14 (q, J = 7.1 Hz, 2 H), 2.51 (s, 3 H), 2.32 (s, 3 H), 1.28 ppm (t, J = 7.1 Hz, 3 H); 13C NMR (100 MHz, CDCl3): d = 137.6, 137.2, 135.9, 130.4, 129.4, 129.1, 128.7, 121.4, 118.9, 118.8, 109.4, 108.5, 38.6, 21.3, 15.3, 9.2 ppm; HRMS (ESI): m/z calcd for C18H20N: 250.1596 [M+H] + ; found: 250.1598.
5-Chloro-1-methyl-2-(p-tolyl)-1H-indole (3 s) Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.60 (s, 1 H), 7.41 (d, J = 7.8 Hz, 2 H), 7.32–7.29 (m, 3 H), 7.20 (d, J = 8.6 Hz, 1 H), 6.49 (s, 1 H), 3.74 (s, 3 H), 2.45 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 142.9, 138.1, 136.6, 129.4, 129.3, 129.2, 128.9, 125.4, 121.6, 119.6, 110.5, 100.8, 31.2, 21.3 ppm; HRMS (ESI): m/z calcd for C16H15ClN: 256.0893 [M+H] + ; found: 256.0891.
1-Butyl-3-methyl-2-(p-tolyl)-1H-indole (3 ab)
5-Bromo-1-methyl-2-(p-tolyl)-1H-indole (3 t)[9b]
Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.65 (d, J = 7.8 Hz, 1 H), 7.41 (d, J = 8.1 Hz, 1 H), 7.34 (s, 4 H), 7.30–7.27 (m, 1 H), 7.20 (t, J = 7.4 Hz, 1 H), 4.08 (t, J = 7.4 Hz, 2 H), 2.50 (s, 3 H), 2.30 (s, 3 H), 1.68–1.61 (m, 2 H), 1.25–1.15 (m, 2 H), 0.83 ppm (t, J = 7.3 Hz, 3 H); 13C NMR (100 MHz, CDCl3): d = 137.5, 137.5, 136.2, 130.4, 129.4, 129.0, 128.5, 121.3, 118.8, 118.7, 109.6, 108.4, 43.6, 32.1, 21.3, 20.0, 13.7, 9.3 ppm; HRMS (ESI): m/z calcd for C20H24N: 278.1909 [M+H] + ; found: 278.1910.
1
Colorless solid; H NMR (400 MHz, CDCl3): d = 7.77–7.76 (m, 1 H), 7.41 (d, J = 7.9 Hz, 2 H), 7.34–7.30 (m, 3 H), 7.23 (d, J = 8.7 Hz, 1 H), 6.49 (s, 1 H), 3.73 (s, 3 H), 2.46 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 142.8, 138.0, 136.9, 129.6, 129.3, 129.3, 129.2, 124.2, 122.7, 112.9, 110.9, 100.7, 31.2, 21.3 ppm. Methyl 2-(4-methoxyphenyl)-1-methyl-1H-indole-4-carboxylate (3 u) Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.55 (d, J = 7.2 Hz, 1 H), 7.49 (d, J = 8.2 Hz, 1 H), 7.30–7.25 (m, 3 H), 7.11 (s, 1 H), 6.94 (d, J = 8.2 Hz, 2 H), 3.83 (s, 6 H), 3.26 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 169.4, 157.9, 137.7, 129.45, 129.40, 129.3, 124.7, 123.6, 121.8, 121.0, 117.0, 113.5, 112.8, 55.3, 51.3, 32.9 ppm; HRMS (ESI): m/z calcd for C18H18NO3 : 296.1287 [M+H] + ; found: 296.1284.
Acknowledgements This work was financially supported by the National Science Foundation of China (grant nos. 21372095, 21172092).
1-Ethyl-2-(p-tolyl)-1H-indole (3 v)[9b] Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.68 (d, J = 7.8 Hz, 1 H), 7.45–7.43 (m, 3 H), 7.32 (d, J = 7.8 Hz, 2 H), 7.29–7.25 (m, 1 H), 7.18 (t, J = 7.4 Hz, 1 H), 6.55 (s, 1 H), 4.23 (q, J = 7.2 Hz, 2 H), 2.47 (s, 3 H), 1.36 ppm (t, J = 7.2 Hz, 3 H); 13C NMR (100 MHz, CDCl3): d = 141.1, 137.8, 137.0, 130.2, 129.2, 129.1, 128.3, 121.3, 120.5, 119.7, 109.8, 101.7, 38.7, 21.3, 15.4 ppm.
[1] a) R. H. Thomson, The Chemistry of Natural Products, Blackie, Son, Glasgow, 1985; b) K. G. B. Torssell, Natural Product Chemistry, Wiley, Chichester, 1983; c) K. Yamamura, S. Ono, H. Ogoshi, H. Masuda, Y. Kuroda, Synlett 1989, 18 – 19; d) I. J. Ninomiya, Nat. Prod. 1992, 55, 541 – 546; e) R. J. Sundberg, Indoles, Academic Press, San Diego, CA, 1996; f) J. Roncali, Chem. Rev. 1992, 92, 711 – 738; g) N. K. Garg, R. Sarpong, B. M. Stolz, J. Am. Chem. Soc. 2002, 124, 13179 – 13184; h) S. Cacchi, G. Fabrizi, Chem. Rev. 2005, 105, 2873 – 2920; i) M. Somei, F. Yamada, Nat. Prod. Rep. 2005, 22, 73 – 103. [2] a) S. S. Labadie, E. Teng, J. Org. Chem. 1994, 59, 4250 – 4254; b) E. Vedejs, D. A. Barda, Org. Lett. 2000, 2, 1033 – 1035; c) B. Chauder, A. Larkin, V. Snieckus, Org. Lett. 2002, 4, 815 – 817; d) X. Cai, V. Snieckus, Org. Lett. 2004, 6, 2293 – 2295; e) I. Bennacef, C. N. Haile, A. Schmidt, A. O. Koren, J. P. Seibyl, J. K. Staley, F. Bois, R. M. Baldwin, G. Tamagnan, Bioorg. Med. Chem. 2006, 14, 7582 – 7591; f) R. Dandu, M. Tao, K. A. Josef, E. R. Bacon, R. L. Hudkins, J. Heterocycl. Chem. 2007, 44, 437 – 440; g) Y. B. Liu, G. W. Gribble, Tetrahedron Lett. 2000, 41, 8717 – 8721; h) C. A. Merlic, Y. You, D. M. McInnes, A. L. Zechman, M. M. Miller, Q. Deng, Tetrahedron 2001, 57, 5199 – 5212; i) C. G. Hartung, A. Fecher, B. Chapell, V. Snieckus, Org. Lett. 2003, 5, 1899 – 1902; j) J. Joucla, L. Djakovitch, Adv. Synth. Catal. 2009, 351, 673 – 714. [3] a) B. S. Lane, M. A. Brown, D. Sames, J. Am. Chem. Soc. 2005, 127, 8050 – 8057; b) E. T. Nadres, A. Lazareva, O. Daugulis, J. Org. Chem. 2011, 76, 471 – 483; c) C. Bressy, D. Alberico, M. Lautens, J. Am. Chem. Soc. 2005, 127, 13148 – 13149; d) B. S. Lane, D. Sames, Org. Lett. 2004, 6, 2897 – 2990; e) X. Wang, B. S. Lane, D. Sames, J. Am. Chem. Soc. 2005, 127, 4996 – 4997; f) F. Bellina, S. Cauteruccio, R. Rossi, Eur. J. Org. Chem. 2006, 1379 – 1382; g) B. B. Tour, B. S. Lane, D. Sames, Org. Lett. 2006, 8, 1979 – 1982; h) X. Wang, D. V. Gribkov, D. Sames, J. Org. Chem. 2007, 72, 1476 – 1479; i) Z. Zhang, Z. Hu, Z. Yu, P. Lei, H. Chi, Y. Wang, R. He, Tetrahedron Lett. 2007, 48, 2415 – 2419; j) F. Bellina, C. Calandri, S. Cauteruccio, R.
1-Propyl-2-(p-tolyl)-1H-indole (3 w) Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.70 (d, J = 7.8 Hz, 1 H), 7.46–7.44 (m, 3 H), 7.35–7.29 (m, 3 H), 7.20 (t, J = 7.3 Hz, 1 H), 6.57 (s, 1 H), 4.17 (t, J = 7.8 Hz, 2 H), 2.50 (s, 3 H), 1.85–1.75 (m, 2 H), 0.85 ppm (t, J = 7.3 Hz, 3 H); 13C NMR (100 MHz, CDCl3): d = 141.6, 137.69, 137.3, 130.4, 129.3, 129.1,128.2, 121.3, 120.4, 119.6, 110.0, 101.7, 45.5, 23.3, 21.3, 11.3 ppm; HRMS (ESI): m/z calcd for C18H20N: 250.1596 [M+H] + ; found: 250.1592. 1-Butyl-2-(p-tolyl)-1H-indole (3 x) Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.73 (d, J = 7.7 Hz, 1 H), 7.49–7.46 (m, 3 H), 7.37–7.30 (m, 3 H), 7.23 (t, J = 7.3 Hz, 1 H), 6.59 (s, 1 H), 4.23 (t, J = 7.4 Hz, 2 H), 2.52 (s, 3 H), 1.82–1.74 (m, 2 H), 1.33–1.24 (m, 2 H), 0.91 ppm (t, J = 7.4 Hz, 3 H); 13C NMR (100 MHz, CDCl3): d = 141.4, 137.7, 137.3, 130.3, 129.3, 129.1, 128.2, 121.2, 120.4, 119.6, 109.9, 101.7, 43.7, 32.1, 21.3, 20.0, 13.6 ppm; HRMS (ESI): m/z calcd for C19H22N: 264.1752 [M+H] + ; found: 264.1749. 1-Benzyl-2-(p-tolyl)-1H-indole (3 y) Colorless solid; 1H NMR (400 MHz, CDCl3): d = 7.52 (d, J = 4.8 Hz, 1 H), 7.43 (d, J = 7.6 Hz, 2 H), 7.38–7.32 (m, 3 H), 7.29–7.24 (m, 5 H), 7.13 (d, J = 7.1 Hz, 2 H), 6.73 (s, 1 H), 5.44 (s, 2 H), 2.47 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 141.9, 138.3, 137.9, 137.9, 129.7, 129.3, 129.1, 128.7, 128.3, 127.1, 125.9, 121.7, 120.4, 120.1, 110.5, 101.9, 47.6, 21.2 ppm; HRMS (ESI): m/z calcd for C22H20N: 298.1596 [M+H] + ; found: 298.1598.
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[4]
[5]
[6] [7]
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Rossi, Tetrahedron 2007, 63, 1970 – 1980; k) F. Bellina, F. Benelli, R. Rossi, J. Org. Chem. 2008, 73, 5529 – 5535; l) N. Lebrasseur, I. Larrosa, J. Am. Chem. Soc. 2008, 130, 2926 – 2927; m) N. S. Nandurkar, M. J. Bhanushali, M. D. Bhor, B. M. Bhanage, Tetrahedron Lett. 2008, 49, 1045 – 1048; n) G. Cusati, L. Djakovitch, Tetrahedron Lett. 2008, 49, 2499 – 2502; o) J. Roger, H. Doucet, Adv. Synth. Catal. 2009, 351, 1977 – 1990; p) B. Ligault, I. Petrov, S. I. Gorelsky, K. Fagnou, J. Org. Chem. 2010, 75, 1047 – 1060; q) F. Shibahara, E. Yamaguchi, T. Murai, Chem. Commun. 2010, 46, 2471 – 2473; r) L. Wang, W. B. Yi, C. Cai, Chem. Commun. 2011, 47, 806 – 808; s) S. Islam, I. Larrosa, Chem. Eur. J. 2013, 19, 15093 – 15096; t) H. Dong, C. Limberakis, S. Liras, D. Price, K. James, Chem. Commun. 2012, 48, 11644 – 11646; u) G.-P. Lu, C. Cai, Synlett 2012, 2992 – 2996; v) L. Joucla, N. Batail, L. Djakovitch, Adv. Synth. Catal. 2010, 352, 2929 – 2936; w) Y. Akita, A. Inoue, K. Yamamoto, A. Ohta, T. Kurihara, M. Shimizu, Heterocycles 1985, 23, 2327 – 2333; x) A. F. P. Biajoli, E. T. Penha, C. R. D. Correia, RSC Adv. 2012, 2, 11930 – 11935. a) S. Kirchberg, R. Frçhlich, A. S. Studer, Angew. Chem. Int. Ed. 2009, 48, 4235 – 4238; Angew. Chem. 2009, 121, 4299 – 4302; b) S.-D. Yang, C.-L. Sun, Z. Fang, B.-J. Li, Y. Li, Z.-J. Shi, Angew. Chem. Int. Ed. 2008, 47, 1473 – 1476; Angew. Chem. 2008, 120, 1495 – 1498; c) Y. Huang, T. Ma, P. Huang, D. Wu, Z. Lin, R. Cao, ChemCatChem 2013, 5, 1877 – 1883; d) J. Zhao, Y. Zhang, K. Cheng, J. Org. Chem. 2008, 73, 7428 – 7431. a) N. R. Deprez, D. Kalyani, A. Krause, M. S. Sanford, J. Am. Chem. Soc. 2006, 128, 4972 – 4973; b) R. J. Phipps, N. P. Grimster, M. J. Gaunt, J. Am. Chem. Soc. 2008, 130, 8172 – 8174. Z.-J. Liang, B.-B. Yao, Y.-H. Zhang, Org. Lett. 2010, 12, 3185 – 3187. a) J. Cornella, P. F. Lu, I. Larrosa, Org. Lett. 2009, 11, 5506 – 5509; b) J. Zhou, P. Hu, M. Zhang, S. Huang, M. Wang, W.-P. Su, Chem. Eur. J. 2010, 16, 5876 – 5881. a) D. R. Stuart, K. Fagnou, Science 2007, 316, 1172 – 1175; b) D. R. Stuart, E. Villemure, K. Fagnou, J. Am. Chem. Soc. 2007, 129, 12072 – 12073; c) S. Potavathri, A. S. Dumas, T. A. Dwight, G. R. Naumiec, J. M. Hammann, B. DeBoef, Tetrahedron Lett. 2008, 49,
Chem. Asian J. 2014, 00, 0 – 0
[9]
[10] [11]
[12]
[13] [14]
[15]
6
Lei Wang et al.
4050 – 4053; d) Z. Liang, J. Zhao, Y. Zhang, J. Org. Chem. 2010, 75, 170 – 177; e) A. Garca-Rubia, B. Urones, R. Gmez Arrays, J. C. Carretero, Chem. Eur. J. 2010, 16, 9676 – 9685; f) D. G. Pintori, M. F. Greaney, J. Am. Chem. Soc. 2011, 133, 1209 – 1211; g) S. Potavathri, K. C. Pereira, S. I. Gorelsky, A. Pike, A. P. LeBris, B. DeBoef, J. Am. Chem. Soc. 2010, 132, 14676 – 14681; h) T. Itahara, T. Sakakibara, Synthesis 1978, 607 – 608; i) T. Itahara, Synthesis 1979, 151 – 152; j) T. A. Dwight, N. R. Rue, D. Charyk, R. Josselyn, B. DeBoef, Org. Lett. 2007, 9, 3137 – 3139. a) T. Miao, P. Li, G.-W. Wang, L. Wang, Chem. Asian J. 2013, 8, 3185 – 3190; b) M. Wu, J. Luo, F. Xiao, S. Zhang, G.-J. Deng, H.-A. Luo, Adv. Synth. Catal. 2012, 354, 335 – 340. M. Dçbele, S. Vanderheiden, N. Jung, S. Brse, Angew. Chem. Int. Ed. 2010, 49, 5986 – 5988; Angew. Chem. 2010, 122, 6122 – 6125. a) D. B. Kimball, M. M. Haley, Angew. Chem. Int. Ed. 2002, 41, 3338 – 3351; Angew. Chem. 2002, 114, 3484 – 3498; b) C. Zhu, M, Yamane, Org. Lett. 2012, 14, 4560 – 4563; c) A. Hafner, S. Brse, Adv. Synth. Catal. 2013, 355, 996 – 1000; d) C.-Y. Liu, P. Knochel, Org. Lett. 2005, 7, 2543 – 2546; e) C.-Y. Liu, P. Knochel, J. Org. Chem. 2007, 72, 7106 – 7115; f) J. Zhou, W. Yang, B. Wang, H. Ren, Angew. Chem. Int. Ed. 2012, 51, 12293 – 12297; Angew. Chem. 2012, 124, 12459 – 12463. a) S. Bhattacharya, S. Majee, R. Mukherjee, S. Sengupta, Synth. Commun. 1995, 25, 651 – 657; b) S. Sengupta, S. K. Sadhukkan, Tetrahedron Lett. 1998, 39, 715 – 718; c) S. Sengupta, S. K. Sadhukkan, Org. Synth. 2002, 79, 52 – 56. S. Brse, M. Schroen, Angew. Chem. Int. Ed. 1999, 38, 1071 – 1073; Angew. Chem. 1999, 111, 1139 – 1142. a) T. Saeki, E.-C. Son, K. Tamao, Org. Lett. 2004, 6, 617 – 619; b) T. Saeki, T. Matsunaga, E.-C. Son, K. Tamao, Adv. Synth. Catal. 2004, 346, 1689 – 1692. M. F. Ibad, D. S. Zinad, M. Hussain, A. Ali, A. Villinger, P. Langer, Tetrahedron 2013, 69, 7492 – 7504. Received: March 22, 2014 Published online: && &&, 0000
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FULL PAPER CH Functionalization Can Liu, Tao Miao, Lei Zhang, Pinhua Li, Yicheng Zhang, &&&&—&&&& Lei Wang*
Seeing to C2: An efficient Pd-catalyzed C2 arylation of N-substituted indoles with 1-aryltriazenes for the synthesis of 2-arylindoles has been developed. In the presence of BF3·OEt2 and palladium(II) acetate,
N-substituted indoles reacted with 1aryltriazenes in N,N-dimethylacetamide to afford the corresponding aryl– indole-type products in good to excellent yields.
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Palladium-Catalyzed Direct C2 Arylation of N-Substituted Indoles with 1Aryltriazenes
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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