Amination of 2

Nov 30, 2017 - Palladium-Catalyzed Sequential Vinylic C–H Arylation/Amination of 2-Vinylanilines with Aryl boronic Acids: Access to 2-Arylindoles. R...
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Article Cite This: J. Org. Chem. 2018, 83, 323−329

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Palladium-Catalyzed Sequential Vinylic C−H Arylation/Amination of 2‑Vinylanilines with Aryl boronic Acids: Access to 2‑Arylindoles Ruixia Yu, Dejun Li, and Fanlong Zeng* Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry & Materials Science, Northwest University, 1 Xuefu Road, Xi’an, Shaanxi 710127, P. R. China S Supporting Information *

ABSTRACT: A palladium-catalyzed selective and successive vinylic C−H arylation/amination of 2-vinylanilines with arylboronic acids to generate indoles has been developed. This procedure represents a straightforward and practical approach to valuable multifunctionalized indoles.

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INTRODUCTION Indoles represent one of the most important classes of heterocyclic motifs, which are ubiquitously observed in naturally occurring bioactive alkaloids and pharmaceuticals.1 Consequently, many efforts have been made by exploring efficient approaches to indole skeletons. Nowadays, numerous elegant protocols are available to fulfill this purpose.2 Among them, oxidative heteroannulation of 2-vinylanilines is an appealing alternative from both atom- and step-economic points of view. The pioneer work of Hegedus et al.3 have been followed by numerous modified procedures to achieve the C− N bond formation. Palladium-catalyzed oxidative amination reactions have proven to be efficient and powerful, and many of them have been successfully applied in synthetic organic chemistry.4 Recently, a new class of alternative approaches based on nitrogen-centered radicals or cation addition to the vinyl to build the C−N bond have been developed by the research groups of Zheng,5 Chemler,6 Youn,7 and Deng,8 independently. Very recently, the intramolecular amination of 2-vinylanilines mediated by the electrophilic cation of main group elements, such as iodine and selenium, is described by Mũniz,9 Deng,10 Breder,11 and Zhao.12 Despite the remarkable advances in the catalytic oxidative heteroannulation, the construction of C2-selectively functionalized indoles via sequential 1,1-difunctionalization of the terminal vinyl on 2vinylanlines has not been reported. Given the advantages of C−H bond activation,13 our group is interested in exploring new efficient procedures to convert 2vinylanilines to potentially useful nitrogen-containing heterocycles through palladium-catalyzed oxidative heteroannulation reactions.14 Importantly, during the investigation, we found that the vinylic C(sp2)−H bond activation is via nucleophilic attack of the conjugated alkene on the electrophilic palladium(II) followed by a base-assisted deprotonation process (Scheme 1),14 which offers the possibility to sequentially difunctionalize the terminal vinyl group of 2-vinylanilines. Arylboronic acids have been successfully employed in oxidative Heck reactions15 and C(sp2)−H bond arylation;16 we envisage that arylboronic acids are suitable arylation reagents for the stepwise © 2017 American Chemical Society

Scheme 1. Pd-Catalyzed Vinylic C−H Bond Activation of 2Vinylanilnes

difuctionalization of the terminal vinyl group on 2-vinylanilines under oxidative conditions. We herein disclose a novel sequential vinylic C−H arylation/amination of 2-vinylanilines with arylboronic acids to generate 2-arylindoles.

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RESULTS AND DISCUSSION Initially, the reaction of Ts-protected aniline 1a with 4methoxyphenyl boronic acid (2a) was chosen as the model reaction to explore the feasibility and efficiency of the domino protocol (Table 1). The nature of the solvent had a significant impact on the reaction efficiency and selectivity. Dioxane and THF offered excellent conversions, but poor selectivities, furnishing mixtures of three products, 3aa, 3aa′, and 3aa″ (Table 1, entries 1 and 2). Toluene and dichloroethane selectively delivered product 3aa′, yet in poor yields (Table 1, entries 3 and 4). DMF and CH3CN eliminated the formation of the direct amination product 3aa″, and DMF gave a better yield of the vinylic C−H arylation product 3aa′ (Table 1, entries 5 and 6). The configuration of the C−C double bond in 3aa′ is Z, determined by X-ray crystallographic analysis. (See the Supporting Information.) Next, we chose DMF as the solvent to examine oxidants. The utilization of organic oxidants, such as PhI(OAc)2 and DDQ, was prone to result in the direct amination product 3aa″, without engaging boronic acid 2a, which is consistent with the results reported by Youn’s group7b (Table 1, entries 7 and 9). Employing silver salts as oxidants, e.g., Ag2CO3, AgOAc, and Ag2O, selectively produced the anticipated product 3aa, and the best performer Ag2CO3 Received: October 27, 2017 Published: November 30, 2017 323

DOI: 10.1021/acs.joc.7b02728 J. Org. Chem. 2018, 83, 323−329

Article

The Journal of Organic Chemistry Table 1. Optimization of Reaction Conditionsa

Table 2. Scope of 2-Vinylanilinesa,b

entry

compound 1

oxidant

solvent

3/3′/3″ yield (%)b

1 2 3 4c 5 6 7 8 9 10 11 12 13d 14e 15 16 17

1a 1a 1a 1a 1a 1a 1a 1a 1a 1a 1a 1a 1a 1a 1b 1c 1d

Cu(OAc)2·H2O Cu(OAc)2·H2O Cu(OAc)2·H2O Cu(OAc)2·H2O Cu(OAc)2·H2O Cu(OAc)2·H2O PhI(OAc)2 BQ DDQ Ag2CO3 AgOAc Ag2O Ag2CO3 Ag2CO3 Ag2CO3 Ag2CO3 Ag2CO3

dioxane THF PhMe DCE CH3CN DMF DMF DMF DMF DMF DMF DMF DMF DMF DMF DMF DMF

18/50/20 20/55/18 −/18/trace −/20/trace 10/69/trace 10/50/trace −/−/10 trace/35/20 trace/−/56 80/−/trace 40/−/trace 46/−/trace 67/−/3 51/−/trace 75/−/10 10/21/− 22/−/−

a All reactions were carried out with 0.3 mmol of 1, 0.6 mmol of 2a, 10 mol % Pd(OAc)2, 5.0 equiv of [Cu2+], [Ag+], PhI(OAc)2, BQ, or DDQ, and 5 mL of a solvent in a sealed flask at 120 °C for 12 h. b Isolated yield. cDCE = dichloroethane. dPdCl2. ePd(OTf)2.

a

All reactions were carried out with 0.3 mmol of 1, 0.6 mmol of 2a, 10 mol % Pd(OAc)2, 2.5 equiv of Ag2CO3, and 5 mL of DMF in a sealed flask at 120 °C for 12 h. bIsolated yield. cThe yield of the direct amination product 3″.

furnished indole 3aa in 80% yield (Table 1, entries 10−12). Utilizing PdCl2 or Pd(OTf)2 as the catalyst precursor, rather than Pd(OAc)2, depressed the yields (Table 1, entries 13 and 14). It is noteworthy that the protecting group Ts also played a key role in this transformation. Using Ms (1b) or Ac (1c) as the protecting group instead of Ts gave inferior results. Interestingly, the free amine 1d was also successfully converted to indole 3da, albeit in a poor yield. With the optimized reaction conditions established, the scope and limitations were investigated by the reaction of 4methoxyphenyl boronic acid with various 2-vinylanilinic substrates, and the results are summarized in Table 2. Both electron-donating and electron-withdrawing groups, such as methyl (3e), methoxy (3f), and chloro (3g), para to the nitrogen were well-tolerated. The strong electron-withdrawing substituent NO2 para to the nitrogen hampered the reaction efficiency, and the para-nitro product 3ha was obtained in 51% yield. Steric hindrance from the methyl group ortho to the nitrogen (1i) markedly affected the outcome of this process, and the yield of 3ia decreased to 30%. When R2 were 4-MeOphenyl, 3-MeO-phenyl, 4-Me-phenyl, and 4-Cl-phenyl, the corresponding products 3ja−3ma were isolated in good to excellent yields, revealing that the substituents on the phenyl group have no major impact on this transformation. The substrates were smoothly converted to the desired products when R1 was a substituent rather than an H atom, and R2 was a functionalized phenyl group (3n, 3o, and 3p). Utilizing a methyl or i-propyl instead of an aromatic group depressed the

reaction efficiency (3qa, 3ra, and 3sa). It is worth mentioning that, when R2 was an H atom, the reaction efficiency dropped significantly, giving the desired product in 14% yield. Gratifyingly, this procedure is also applicable to the 2vinylnaphthalen-1-amine derivatives. The substrates 1t and 1u furnished the corresponding products in moderate yields (58% and 52%). The generality of aryl boronic acids was next examined by the reaction of Ts-protected aniline 1a with a range of aryl boronic acids (Table 3). The results show that the electronic properties of the substituents have a significant effect on the efficiency of this reaction. Three different phenyl boronic acids with strong electron-donating methoxy groups gave good yields, regardless of the effect of steric hindrance from the MeO groups (Table 3, entries 1−3). Phenyl boronic acids with weak electron-donating methyl groups offered moderate yields (Table 3, entries 4−6). The unfunctionalized phenyl boronic acid produced the desired product 3ag in a poor yield (37%) at 120 °C, while elevating the reaction temperature to 150 °C increased the yield of 3ag to 79%. At the elevated temperature, the phenyl boronic acids with electron-deficient groups, e.g., 4Ph (2h), 4-Cl (2i), 4-CN (2j), 4-CF3 (2l), and 4-MeCO (2m), furnished the anticipated products in good yields. The limitations encountered with 4-methoxycarbonylphenylboronic acid resulted in the indole product 3ak in a poor yield. 1Naphthyl boronic acid was also a suitable coupling partner, 324

DOI: 10.1021/acs.joc.7b02728 J. Org. Chem. 2018, 83, 323−329

Article

The Journal of Organic Chemistry Table 3. Scope of Aryl Boronic Acidsa

Scheme 2. Control Experiments

entry

compound 2

R3

compound 3

yield (%)b

1 2 3 4 5 6 7 8 9 10 11 12 13 14

2a 2b 2c 2d 2e 2f 2g 2h 2i 2j 2k 2l 2m 2n

4-MeO 2-MeO 2,6-di-MeO 4-Me 2-Me 3,5-di-Me H 4-Ph 4-Cl 4-CN 4-CO2Me 4-CF3 4-MeCO benzo[b]

3aa 3ab 3ac 3ad 3ae 3af 3ag 3ah 3ai 3aj 3ak 3al 3am 3an

80 71 83 63 63 61 79c 65c 66 61 35 57c 62c 68c

a

All reactions were carried out with 0.3 mmol of 1a, 0.6 mmol of 2, 10 mol % Pd(OAc)2, 2.5 equiv of Ag2CO3, and 5 mL of DMF in a sealed flask at 120 °C for 12 h. bIsolated yield. cT = 150 °C.

giving the anticipated product 3an in 68% yield. It is noteworthy that this procedure is not applicable to heteroaryl boronic acids, such as 2-furanboronic acid, 2-pyridineboronic acid, and 4-pyridineboronic acid. To gain a mechanistic insight for the reaction, the following control experiments were conducted (Scheme 2). Decreasing the reaction temperature to 90 °C led to the formation of 3aa′ in 40% yield with a trace amount of 3aa (Scheme 2, eq 1). Subjecting 3aa′ to the optimized conditions gave the product 3aa in 94% yield (Scheme 2, eq 2), which manifests the intermediacy of the vinylic C−H arylation product 3aa′ in this transformation. Employing Ag2CO3 or a catalytic amount of Pd(OAc)2 with oxidant Cu(OAc)2 achieved the intramolecular amination to generate indole 3aa, albeit with worse performance than that under optimized conditions (Scheme 2, eq 3 and 5), which indicates that silver and palladium with an oxidant can promote the amination step, independently. The Ag2CO3promoted intramolecular amination was slightly affected by TEMPO (2,2,6,6-tetramethylpiperidine-N-oxyl), but deterred by BHT (3,5-di-tert-butyl-4-hydroxytoluene), which is consistent with the observation of Youn’s group7a and shows that the reaction possibly involves a free-radical process (Scheme 2, eq 4). Performing the reaction of 1a and 2a under the optimized conditions but without the presence of Pd(OAc)2 resulted in indole 3aa″ (77%), revealing that the catalyst precursor Pd(OAc)2 is a requisite for vinylic C−H arylation (Scheme 2, eq 7). On the basis of the above observations, a possible mechanism for this transformation is outlined in Scheme 3, with 1a and 2g as the model substrates. Initially, the nitrogen atom of aniline 1a adds to the Pd(II) species 4 with elimination of acetic acid, followed by the formation of palladacycle complex 5 via vinylic C−H bond activation.14 The Pd(II) species 5 transmetalates with boronic acid 2g to give the palladium species 6. Reductive elimination of 6 affords the intermediate product 3ag′ and releases the palladium(0) species, which is reoxidized to the active Pd(II) species by Ag2CO3. There are two pathways to

form the desired product 3ag. In path a, an intramolecular nucleophilic attack of the conjugated alkene on the electrophilic palladium(II), followed by a base-assisted deprotonation, results in the key palladacycle complex 8. Reductive elimination of 8 engenders product 3ag, along with the palladium(0) species, which then is reoxidized by Ag2CO3 to the palladium(II) species 4. In pathway b, the intermediate product 3ag′ is oxidized by Ag2CO3 to the nitrogen radical cation 9, the electronphilicity of which triggers intramolecular annulation to afford the benzylic radical 10, with the loss of a proton. Hereafter, Ag2CO3 oxidizes radical 10 to the benzylic 325

DOI: 10.1021/acs.joc.7b02728 J. Org. Chem. 2018, 83, 323−329

Article

The Journal of Organic Chemistry Scheme 3. Proposed Catalytic Cycle

128.9, 127.8, 127.3, 124.8, 121.2, 115.2, 114.2, 55.4, 21.7. HRMS (ESITOF) m/z: [M + Na]+ calcd for C22H21NO3SNa, 402.1140; found, 402.1142. 2-(1-(3-Methoxyphenyl)vinyl)-N-tosylbenzenamine (1k). White solid (0.7 g, 37% yield), mp 96−97 °C. 1H NMR (400 MHz, CDCl3): δ 7.74 (d, J = 8.0 Hz, 1H), 7.47 (d, J = 8.0 Hz, 2H), 7.36 (t, J = 8.0 Hz, 1H), 7.21 (t, J = 8.0 Hz, 1H), 7.15 (d, J = 8.0 Hz, 4H), 6.89 (d, J = 8.0 Hz, 1H), 6.69 (d, J = 8.0 Hz, 1H), 6.57 (d, J = 8.0 Hz, 2H), 5.71 (s, 1H), 4.93 (s, 1H), 3.75 (s, 3H), 2.40 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 159.9, 144.9, 143.8, 140.2, 135.9, 134.2, 133.2, 130.6, 129.9, 129.5, 129.0, 127.3, 124.9, 121.3, 118.9, 117.5, 113.9, 112.2, 55.2, 21.6. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C22H22NO3S, 380.1320; found 380.1313. 2-(1-p-Tolylvinyl)-N-tosylbenzenamine (1l). White solid (1.11 g, 61% yield), mp 73−74 °C. 1H NMR (400 MHz, CDCl3): δ 7.79 (d, J = 8.0 Hz, 1H), 7.50 (d, J = 8.0 Hz, 2H), 7.37 (t, J = 8.0 Hz, 1H), 7.16 (d, J = 8.0 Hz, 4H), 7.08 (d, J = 8.0 Hz, 2H), 6.98 (d, J = 8.0 Hz, 2H), 6.62 (s, 1H), 5.69 (s, 1H), 4.87 (s, 1H), 2.42 (s, 3H), 2.40 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 144.8, 143.7, 138.5, 136.0, 135.8, 134.2, 133.4, 130.5, 129.5, 129.4, 128.8, 127.2, 126.2, 124.8, 121.2, 116.2, 21.5, 21.2. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C22H22NO2S, 364.1371; found, 364.1366. 2-(1-(4-Chlorophenyl)vinyl)-N-tosylbenzenamine (1m). White solid (0.57 g, 30% yield), mp 65−66 °C. 1H NMR (400 MHz, CDCl3): δ 7.76 (d, J = 8.0 Hz, 1H), 7.41 (d, J = 8.0 Hz, 2H), 7.33 (t, J = 8.0 Hz, 1H), 7.10 (t, J = 8.0 Hz, 5H), 7.03 (d, J = 8.0 Hz, 1H), 6.90 (d, J = 8.0 Hz, 2H), 6.54 (s, 1H), 5.74 (s, 1H), 4.98 (s, 1H), 2.38 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 144.0, 143.9, 137.2, 136.1, 134.5, 134.3, 132.5, 130.5, 129.6, 129.2, 128.9, 127.6, 127.1, 124.9, 121.1, 117.7, 21.6. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C21H18ClNO2SNa, 406.0644; found, 406.0621. General Procedure for the Palladium-Catalyzed Reaction of 2-Vinylanilines with Aryl Boronic Acids. A mixture of Pd(OAc)2 (0.03 mmol), Ag2CO3 (0.75 mmol), 1 (0.3 mmol), 2 (0.6 mmol), and DMF (5 mL) was added sequentially to a heavy glass flask. The reaction mixture was stirred and heated at 120 °C for 12 h. After the reaction cooled to rt, the solvent was removed under reduced pressure. The residue was purified by chromatography on silica gel to afford the desired product 3. 2-((Z)-2-(4-Methoxyphenyl)-1-phenylvinyl)-N-tosylbenzenamine (3aa′). White solid (94 mg, 69% yield), mp 167−168 °C. 1H NMR (400 MHz, CDCl3): δ 7.69 (d, J = 8.0 Hz, 1H), 7.36 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.0 Hz, 1H), 7.25−7.18 (m, 3H), 7.07 (t, J = 8.0 Hz, 5H), 6.98 (d, J = 8.0 Hz, 2H), 6.79 (d, J = 8.0 Hz, 2H), 6.70 (br s,

carbocation 11, followed by the constitution of the desired product 3ag by deprotonation. In conclusion, a novel access to highly valuable indoles has been developed based on palladium-catalyzed sequential vinylic C−H arylation/amination of 2-vinylanilines with aryl boronic acids. This procedure, tolerating a wide range of typical organic functional groups, represents a straightforward and practical approach to multifunctionalized indoles. To our knowledge, it is the first example of a selective and successive 1,1difunctionalization of the terminal vinyl on 2-vinylanlines to construct indoles, and we thereupon believe it provides a basis for exploring new transformations of 2-vinylanilines or their analogues to valuable nitrogen-containing heterocycles.

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EXPERIMENTAL SECTION

General information. Unless otherwise noted, all of the materials were purchased from commercial suppliers and used as received. Solvents were freshly distilled by standard procedures prior to use. All 1 H and 13C{1H} NMR spectra were recorded on a Bruker 400 MHz spectrometer. The NMR chemical shift values refer to CDCl3 (δ (1H), 7.26 ppm; δ (13C), 77.16 ppm). Mass spectra were obtained on a micrOTOF-Q II mass spectrometer. Crystals were collected on a Bruker SMART APEX II CCD (Mo Kα radiation, λ = 0.710 73 Å). The corresponding 2-vinylanilines used to prepare 1a−1i,17 1o,17 1p,17 1t,17 1u,17 1j−1m,18 1r,18 and 1s18 were synthesized by known literature methods. General Procedure for the Preparation of New 2-Vinyl-Ntosylanilines. The corresponding 2-vinylaniline (5.00 mmol) was dissolved in dry pyridine (25 mL), and the solution was treated with 4toluenesulfonyl chloride (5.50 mmol) at 0 °C. The mixture was stirred at room temperature for 2 h, then poured into water, and extracted with CH2Cl2. The combined organic phases were dried over Mg2SO4, filtered, and concentrated in a vacuum. The reaction mixture was purified directly by flash chromatography, using a mixture of petroleum ether and ethyl acetate (v/v = 15:1) as the eluent. 2-(1-(4-Methoxyphenyl)vinyl)-N-tosylbenzenamine (1j). White solid (1.25 g, 66% yield), mp 85−86 °C. 1H NMR (400 MHz, CDCl3): δ 7.70 (d, J = 8.0 Hz, 1H), 7.44 (d, J = 8.0 Hz, 2H), 7.31 (t, J = 8.0 Hz, 1H), 7.10 (t, J = 8.0 Hz, 3H), 7.06 (d, J = 8.0 Hz, 1H), 6.94 (d, J = 8.0 Hz, 2H), 6.73 (d, J = 8.0 Hz, 2H), 6.57 (s, 1H), 5.57 (s, 1H), 4.76 (s, 1H), 3.81 (s, 3H), 2.37 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 160.0, 144.4, 143.8, 136.1, 134.3, 133.5, 131.2, 130.5, 129.5, 326

DOI: 10.1021/acs.joc.7b02728 J. Org. Chem. 2018, 83, 323−329

Article

The Journal of Organic Chemistry 1H), 6.61 (d, J = 8.0 Hz, 2H), 3.75 (s, 3H), 2.30 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 159.3, 143.6, 141.1, 136.2, 134.6, 134.2, 131.3, 130.6, 130.4, 130.1, 129.6, 129.1, 128.7, 128.5, 127.8, 127.3, 126.5, 124.8, 119.2, 113.9, 55.3, 21.6. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C28H25NO3SNa, 478.1453; found, 478.1465 2-(4-Methoxyphenyl)-3-phenyl-1-mesyl-1H-indole (3ba). White solid (91 mg, 75% yield), mp 156−157 °C. 1H NMR (400 MHz, CDCl3): δ 8.20 (d, J = 8.0 Hz, 1H), 7.60 (d, J = 8.0 Hz, 1H), 7.41 (t, J = 8.0 Hz, 1H), 7.37 (d, J = 8.0 Hz, 1H), 7.29 (d, J = 8.0 Hz, 4H), 7.23 (t, J = 8.0 Hz, 3H), 6.84 (d, J = 8.0 Hz, 2H), 3.80 (s, 3H), 2.85 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 160.0, 137.0, 133.2, 132.8, 130.4, 130.0, 128.5, 127.2, 125.4, 124.5, 124,3, 122.8, 120.3, 115.8, 113.3, 55.3, 40.6. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C22H19NO3S Na, 400.0983; found, 400.0966. N-(2-((Z)-2-(4-Methoxyphenyl)-1-phenylvinyl)phenyl)acetamide (3ca′). White solid (22 mg, 21% yield), mp 189−190 °C. 1H NMR (400 MHz, CDCl3): δ 8.30 (d, J = 8.0 Hz, 1H), 7.15−7.38 (m, 1H), 7.36−7.28 (m, 5H), 7.22 (br s, 1H), 7.15 (d, J = 4.0 Hz, 3H), 6.98 (d, J = 8.0 Hz, 2H), 6.70 (d, J = 8.0 Hz, 2H), 3.74 (s, 3H), 1.79 (s, 3H). 13 C NMR (101 MHz, CDCl3): δ 168.3, 159.3, 142.0, 135.6, 135.2, 130.8, 130.4, 129.9, 129.8, 128.9, 128.8, 127.9, 126.7, 124.7, 121.4, 114.0, 55.3, 24.6. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C23H21NO2Na, 366.1470; found, 366.1459. 2-(4-Methoxyphenyl)-3-phenyl-5-methyl-1-tosyl-1H-indole (3ea). White solid (93 mg, 66% yield), mp 172−173 °C. 1H NMR (400 MHz, CDCl3): δ 8.25 (d, J = 8.0 Hz, 1H), 7.29 (d, J = 8.0 Hz, 2H), 7.25−7.16 (m, 5H), 7.14 (d, J = 8.0 Hz, 2H), 7.09−7.05 (m, 3H), 7.03 (s, 1H), 6.78 (d, J = 8.0 Hz, 2H), 3.80 (s, 3H), 2.37 (s, 3H), 2.28 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 159.7, 144.5, 137.1, 135.6, 135.4, 140.0, 133.4, 133.1, 130.9, 130.0, 129.3, 128.3, 127.0, 126.9, 126.5, 124.4, 123.2, 119.8, 116.2, 112.9, 55.3, 21.7, 21.4. HRMS (ESITOF) m/z: [M + H]+ calcd for C29H26NO3S, 468.1633; found, 468.1616. 2-(4-Methoxyphenyl)-3-phenyl-5-methoxy-1-tosyl-1H-indole (3fa). White solid (136 mg, 94% yield), mp 187−188 °C. 1H NMR (400 MHz, CDCl3): δ 8.24 (d, J = 12.0 Hz, 1H), 7.25 (d, J = 8.0 Hz, 2H), 7.20−7.16 (m, 3H), 7.11 (d, J = 8.0 Hz, 2H), 7.05−6.99 (m, 4H), 6.95 (d, J = 8.0 Hz, 1H), 6.84 (s, 1H), 6.76 (d, J = 8.0 Hz, 2H), 3.77 (s, 3H), 3.73 (s, 3H), 2.25 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 159.8, 157.2, 144.5, 137.9, 135.1, 133.4, 133.0, 131.9, 129.8, 129.3, 128.4, 127.0, 127.0, 124.7, 123.1, 117.5, 113.7, 112.9, 102.4, 55.7, 55.3, 21.7. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C29H25NO4SNa, 506.1402; found, 506.1383. 2-(4-Methoxyphenyl)-3-phenyl-5-chloro-1-tosyl-1H-indole (3ga). White solid (95 mg, 65% yield), mp 186−187 °C. 1H NMR (400 MHz, CDCl3): δ 8.24 (d, J = 8.0 Hz, 1H), 7.34 (s, 1H), 7.26 (d, J = 8.0 Hz, 1H), 7.20 (d, J = 8.0 Hz, 2H), 7.16−7.10 (m, 3H), 7.06 (d, J = 8.0 Hz, 2H), 6.99 (t, J = 8.0 Hz, 4H), 6.72 (d, J = 8.0 Hz, 2H), 3.74 (s, 3H), 2.23 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 160.0, 144.9, 138.3, 135.6, 135.1, 133.5, 132.3, 131.9, 130.1, 129.8, 129.5, 128.5, 127.2, 127.0, 125.2, 123.8, 122.5, 119.5, 117.5, 113.0, 55.3, 21.7. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C28H22ClNO3SNa, 510.0907; found, 510.0907. 2-(4-Methoxyphenyl)-3-phenyl-5-nitro-1-tosyl-1H-indole (3ha). White solid (76 mg, 51% yield), mp 205−206 °C. 1H NMR (400 MHz, CDCl3): δ 8.54 (d, J = 8.0 Hz, 1H), 8.38 (s, 1H), 8.28 (d, J = 8.0 Hz, 1H), 7.31 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 3H), 7.15−7.10 (m, 6H), 6.81 (d, J = 8.0 Hz, 2H), 3.84 (s, 3H), 2.34 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 160.3, 145.6, 144.9, 140.2, 139.7, 135.3, 133.6, 131.5, 130.3, 129.8, 129.7, 128.7, 127.7, 127.2, 124.3, 121.8, 120.1, 116.4, 116.3, 113.1, 55.4, 21.8. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C28H22N2O5SNa, 521.1147; found, 521.1165. 2-(4-Methoxyphenyl)-3-phenyl-7-methyl-1-tosyl-1H-indole (3ia). White solid (41 mg, 30% yield), mp 179−180 °C. 1H NMR (400 MHz, CDCl3): δ 7.24−7.19 (m, 4H), 7.15 (t, J = 8.0 Hz, 1H), 7.09 (d, J = 8.0 Hz, 2H), 6.95 (d, J = 8.0 Hz, 3H), 6.90 (d, J = 8.0 Hz, 2H), 6.82 (d, J = 8.0 Hz, 2H), 6.74 (d, J = 8.0 Hz, 2H), 3.78 (s, 3H), 2.85 (s, 3H), 2.30 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 159.6, 144.3, 140.3, 140.2, 135.9, 133.2, 132.8, 132.4, 131.3, 129.3, 128.8, 128.6, 128.4, 127.9, 127.4, 127.2, 125.9, 123.9, 117.5, 113.0, 55.3, 21.7, 21.6.

HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C29H25NO3SNa, 490.1453; found, 490.1440. 2-(4-Methoxyphenyl)-3-(3-methoxyphenyl)-1-tosyl-1H-indole (3ka). White solid (99 mg, 68% yield), mp 160−161 °C. 1H NMR (400 MHz, CDCl3): δ 8.42 (d, J = 8.0 Hz, 1H), 7.53 (d, J = 8.0 Hz, 1H), 7.42 (d, J = 8.0 Hz, 1H), 7.34 (d, J = 8.0 Hz, 2H), 7.29 (t, J = 8.0 Hz, 1H), 7.19−7.14 (m, 3H), 7.08 (d, J = 8.0 Hz, 2H), 6.83 (d, J = 8.0 Hz, 2H), 6.74 (t, J = 8.0 Hz, 2H), 6.64 (s, 1H), 3.84 (s, 3H), 3.63 (s, 3H), 2.32 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 159.9, 159.4, 144.6, 137.3, 136.9, 135.5, 134.3, 133.5, 130.4, 129.4, 129.3, 127.0, 125.1, 124.3, 123.3, 122.4, 120.0, 116.4, 115.3, 112.9, 112.8, 55.3, 55.1, 21.7. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C29H25NO4SNa, 506.1402; found, 506.1391. 2-(4-Methoxyphenyl)-3-p-tolyl-1-tosyl-1H-indole (3la). White solid (90 mg, 64% yield), mp 167−168 °C. 1H NMR (400 MHz, CDCl3): δ 8.37 (d, J = 8.0 Hz, 1H), 7.44 (d, J = 8.0 Hz, 1H), 7.35 (t, J = 8.0 Hz, 1H), 7.29 (d, J = 8.0 Hz, 2H), 7.23 (t, J = 8.0 Hz, 1H), 7.14 (d, J = 8.0 Hz, 2H), 7.05−6.99 (m, 4H), 6.96 (d, J = 8.0 Hz, 2H), 6.78 (d, J = 8.0 Hz, 2H), 3.79 (s, 3H), 2.25 (s, 6H). 13C NMR (101 MHz, CDCl3): δ 159.7, 144.6, 137.3, 136.7, 136.6, 135.5, 133.5, 130.7, 129.8, 129.8, 129.3, 129.1, 127.0, 125.0, 124.4, 124.2, 123.2, 112.0, 116.4, 112.9, 55.2, 21.6, 21.3. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C29H25NO3SNa, 490.1453; found, 490.1447. 2-(4-Methoxyphenyl)-3-(2-chlorophenyl)-5-chloro-1-tosyl-1H-indole (3na). White solid (129 mg, 82% yield), mp 206−207 °C. 1H NMR (400 MHz, CDCl3): δ 8.26 (d, J = 8.0 Hz, 1H), 7.35 (d, J = 8.0 Hz, 1H), 7.30 (d, J = 8.0 Hz, 1H), 7.22 (d, J = 8.0 Hz, 2H), 7.18 (d, J = 8.0 Hz, 1H), 7.08 (d, J = 8.0 Hz, 1H), 7.06−7.02 (m, 3H), 6.87 (d, J = 8.0 Hz, 1H), 6.74 (d, J = 8.0 Hz, 2H), 3.76 (s, 3H), 2.29 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 160.0, 144.9, 140.0, 135.8, 134.9, 134.7, 132.7, 132.4, 132.3, 131.6, 130.3, 129.6, 129.4, 126.9, 125.2, 122.7, 122.5, 119.7, 118.0, 112.9, 55.2, 21.7. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C28H21Cl2NO3SNa, 544.0517; found, 544.0509. 2-(4-Methoxyphenyl)-3-p-tolyl-5-methyl-1-tosyl-1H-indole (3oa). White solid (108 mg, 75% yield), mp 185−186 °C. 1H NMR (400 MHz, CDCl3): δ 8.23 (d, J = 8.0 Hz, 1H), 7.28 (d, J = 8.0 Hz, 2H), 7.20 (s, 1H), 7.18−7.11 (m, 3H), 7.03−6.91 (m, 6H), 6.77 (d, J = 8.0 Hz, 2H), 3.77 (s, 3H), 2.34 (s, 3H), 2.24 (s, 6H). 13C NMR (101 MHz, CDCl3): δ 159.7, 144.4, 136.8, 136.5, 135.5, 135.3, 133.9, 133.4, 131.0, 130.0, 129.8, 129.3, 129.0, 127.0, 126.4, 124.4, 123.3, 119.8, 116.1, 112.8, 55.2, 21.6, 21.4, 21.3. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C30H27NO3SNa, 504.1609; found, 504.1627. 2-(4-Methoxyphenyl)-3-(4-chlorophenyl)-5-methyl-1-tosyl-1H-indole (3pa). White solid (92 mg, 61% yield), mp 191−192 °C. 1H NMR 400 MHz, CDCl3): δ 8.27 (d, J = 8.0 Hz, 1H), 7.31 (d, J = 8.0 Hz, 2H), 7.24−7.19 (m, 4H), 7.12 (d, J = 8.0 Hz, 2H), 7.07 (d, J = 8.0 Hz, 2H), 7.01 (d, J = 8.0 Hz, 2H), 6.82 (d, J = 8.0 Hz, 2H), 3.85 (s, 3H), 2.41 (s, 3H), 2.32 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 159.0, 144.6, 137.3, 135.5, 134.1, 133.4, 132.8, 131.7, 131.2, 130.4, 129.4, 128.6, 127.0, 126.6, 123.1, 122.9, 119.5, 116.2, 113.0, 55.3, 21.7, 21.5. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C29H24ClNO3SNa, 524.1063; found, 524.1091. 2-(4-Methoxyphenyl)-3-isopropyl-1-tosyl-1H-indole (3qa). White solid (65 mg, 52% yield), mp 156−157 °C. 1H NMR (400 MHz, CDCl3): δ 8.32 (d, J = 8.0 Hz, 1H), 7.64 (d, J = 8.0 Hz, 1H), 7.33 (d, J = 8.0 Hz, 1H), 7.28 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 1H), 7.13 (d, J = 8.0 Hz, 2H), 7.05 (d, J = 8.0 Hz, 2H), 6.91 (d, J = 8.0 Hz, 2H), 3.86 (s, 3H), 2.29 (s, 3H), 1.20 (s, 3H), 1.19 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 159.9, 144.4, 137.6, 135.9, 135.3, 132.9, 129.4, 129.3, 128.7, 126.9, 124.4, 123.9, 123.9, 123.4, 120.7, 116.2, 113.0, 55.4, 26.1, 22.2, 21.6. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C25H25NO3SNa, 442.1453; found, 442.1453. 2-(4-Methoxyphenyl)-3,5-dimethyl-1-tosyl-1H-indole (3ra). White solid (51 mg, 42% yield), mp 171−172 °C. 1H NMR (400 MHz, CDCl3): δ 8.17 (d, J = 8.0 Hz, 1H), 7.28−7.23 (m, 4H), 7.17 (d, J = 8.0 Hz, 2H), 7.03 (d, J = 8.0 Hz, 2H), 6.96 (d, J = 8.0 Hz, 2H), 3.88 (s, 3H), 2.44 (s, 3H), 2.28 (s, 3H), 1.99 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 159.7, 144.3, 136.8, 135.4, 135.3, 133.6, 132.8, 132.2, 129.3, 126.9, 126.2, 123.9, 119.4, 119.0, 116.1, 113.0, 55.4, 21.7, 21.5, 9.6. 327

DOI: 10.1021/acs.joc.7b02728 J. Org. Chem. 2018, 83, 323−329

Article

The Journal of Organic Chemistry HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C24H23NO3SNa, 428.1296; found, 428.1287. 2-(4-Methoxyphenyl)-3-methyl-6-chloro-1-tosyl-1H-indole (3sa). White solid (69 mg, 54% yield), mp 156−157 °C. 1H NMR (400 MHz, CDCl3): δ 8.35 (s, 1H), 7.31 (d, J = 8.0 Hz, 1H), 7.27 (d, J = 8.0 Hz, 3H), 7.21 (d, J = 12.0 Hz, 2H), 7.08 (d, J = 8.0 Hz, 2H), 6.96 (d, J = 8.0 Hz, 2H), 3.89 (s, 3H), 2.32 (s, 3H), 1.99 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 159.9, 144.8, 137.5, 137.3, 135.2, 132.9, 130.7, 130.3, 129.5, 127.0, 124.5, 123.2, 119.7, 118.9, 116.4, 113.1, 55.4, 21.7, 9.5. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C23H20ClNO3SNa, 448.0750; found, 448.0743. 2-(4-Methoxyphenyl)-3-phenyl-1-tosyl-1H-benzo[g]indole (3ta). White solid (88 mg, 58% yield), mp 180−181 °C. 1H NMR (400 MHz, CDCl3): δ 8.88 (d, J = 8.0 Hz, 1H), 7.82 (d, J = 8.0 Hz, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.58 (t, J = 8.0 Hz, 1H), 7.43 (t, J = 8.0 Hz, 1H), 7.22−7.15 (m, 4H), 7.12 (d, J = 8.0 Hz, 2H), 6.87−6.89 (m, 4H), 6.73 (d, J = 8.0 Hz, 4H), 3.75 (s, 3H), 2.22 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 159.7, 144.5, 140.7, 136.1, 133.1, 132.7, 132.7, 132.2, 129.5, 128.7, 128.4, 128.3, 128.3, 127.6, 127.3, 127.3, 126.7, 126.6, 126.0, 125.3, 124.0, 118.2, 113.0, 55.3, 21.7. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C32H25NO3SNa, 526.1453; found, 526.1442. 2-(4-Methoxyphenyl)-3-(4-chlorophenyl)-1-tosyl-1H-benzo[g]indole (3ua). White solid (84 mg, 52% yield), mp 165−166 °C. 1H NMR (400 MHz, CDCl3): δ 8.99 (d, J = 8.0 Hz, 1H), 7.96 (d, J = 8.0 Hz, 1H), 7.79 (d, J = 8.0 Hz, 1H), 7.72 (t, J = 8.0 Hz, 1H), 7.58 (t, J = 8.0 Hz, 1H), 7.34−7.28 (m, 3H), 7.22 (d, J = 8.0 Hz, 2H), 6.98 (d, J = 8.0 Hz, 2H), 6.90 (d, J = 8.0 Hz, 3H), 6.87−6.83 (m, 3H), 3.91 (s, 3H), 2.36 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 159.9, 144.6, 141.0, 136.1, 133.3, 132.8, 132.7, 132.4, 132.1, 131.7, 130.8, 130.0, 129.0, 128.4, 128.3, 127.7, 127.3, 126.9, 126.6, 126.1, 125.4, 123.6, 117.8, 113.2, 55.4, 21.7. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C32H24ClNO3SNa, 560.1063; found, 560.1041. 2-(2-Methoxyphenyl)-3-phenyl-1-tosyl-1H-indole (3ab). White solid (97 mg, 71% yield), mp 182−183 °C. 1H NMR (400 MHz, CDCl3): δ 8.27 (d, J = 8.0 Hz, 1H), 7.48 (d, J = 8.0 Hz, 1H), 7.38 (d, J = 8.0 Hz, 2H), 7.31−7.26 (m, 2H), 7.23−7.07 (m, 6H), 7.03 (d, J = 8.0 Hz, 2H), 6.89 (d, J = 8.0 Hz, 1H), 6.79 (d, J = 8.0 Hz, 1H), 6.75 (d, J = 8.0 Hz, 1H), 3.56 (s, 3H), 2.25 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 159.3, 144.4, 136.9, 136.2, 133.5, 133.3, 133.2, 130.7, 130.1, 129.5, 129.4, 128.2, 127.1, 126.9, 124.8, 124.0, 123.6, 120.5, 120.0, 119.7, 115.5, 110.5, 55.3, 21.6. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C28H23NO3SNa, 476.1296; found, 476.1278. 2-(2,6-Dimethoxyphenyl)-3-phenyl-1-tosyl-1H-indole (3ac). White solid (120 mg, 83% yield), mp 256−257 °C. 1H NMR (400 MHz, CDCl3): δ 8.28 (d, J = 8.0 Hz, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.53 (d, J = 8.0 Hz, 2H), 7.35 (d, J = 8.0 Hz, 1H), 7.31 (d, J = 8.0 Hz, 1H), 7.27 (d, J = 4.0 Hz, 1H), 7.22−7.18 (m, 5H), 7.11 (d, J = 8.0 Hz, 2H), 6.46 (d, J = 8.0 Hz, 2H), 3.49 (s, 6H), 2.32 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 159.9, 144.0, 137.0, 136.9, 133.8, 131.1, 130.1, 129.7, 129.2, 129.1, 128.0, 127.4, 126.8, 124.3, 123.8, 123.2, 119.8, 115.0, 109.5, 103.5, 55.5, 21.6. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C29H25NO4SNa, 506.1402; found, 506.1412. 2-o-Tolyl-3-phenyl-1-tosyl-1H-indole (3ae). White solid (83 mg, 63% yield), mp 147−149 °C. 1H NMR (400 MHz, CDCl3): δ 8.46 (J = 8.0 Hz, 1H), 7.60 (d, J = 8.0 Hz, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.41 (d, J = 8.0 Hz, 2H), 7.34 (d, J = 8.0 Hz, 1H), 7.30 (d, J = 8.0 Hz, 1H), 7.24−7.15 (m, 4H), 7.15−7.09 (m, 5H), 7.03 (d, J = 8.0 Hz, 1H), 2.35 (s, 3H), 1.96 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 144.8, 139.8, 137.0, 136.2, 135.7, 132.9, 132.6, 130.6, 129.9, 129.6, 129.5, 129.5, 129.2, 128.3, 127.3, 127.0, 125.1, 124.7, 123.9, 123.9, 120.1, 115.7, 21.7, 20.3. HRMS (ESI-TOF) m/z: [M + Na] + calcd for C28H23NO2SNa, 460.1347; found, 460.1347. 2-(3,5-Dimethylphenyl)-3-phenyl-1-tosyl-1H-indole (3af). White solid (83 mg, 61% yield), mp 158−159 °C. 1H NMR (400 MHz, CDCl3): δ 8.40 (d, J = 8.0 Hz, 1H), 7.49 (d, J = 8.0 Hz, 1H), 7.41 (d, J = 8.0 Hz, 1H), 7.35 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 8.0 Hz, 1H), 7.25−7.20 (m, 3H), 7.11 (d, J = 8.0 Hz, 2H), 7.08 (d, J = 8.0 Hz, 2H), 6.95 (s, 1H), 6.79 (s, 2H), 2.32 (s, 2H), 2.23 (s, 6H). 13C NMR (101 MHz, CDCl3): δ 144.6, 137.4, 137.3, 136.6, 135.8, 133.0, 130.7, 130.5, 130.3, 130.0, 130.0, 129.3, 128.2, 127.2, 127.0, 125.1, 124.3, 124.1,

120.1, 116.3, 21.7, 21.4. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C29H25NO2SNa, 474.1504; found, 474.1514. 2-([1,1′-Biphenyl]-4-yl)-3-phenyl-1-tosyl-1H-indole (3ah). White solid (97 mg, 65% yield), mp 131−132 °C. 1H NMR (400 MHz, CDCl3): δ 8.34 (d, J = 8.0 Hz, 1H), 7.57 (d, J = 8.0 Hz, 2H), 7.44 (d, J = 8.0 Hz, 2H), 7.42−7.31 (m, 4H), 7.28 (d, J = 8.0 Hz, 3H), 7.24 (d, J = 8.0 Hz, 2H), 7.20 (d, J = 8.0 Hz, 1H), 7.16−7.12 (m, 3H), 7.04 (d, J = 8.0 Hz, 2H), 6.99 (d, J = 8.0 Hz, 2H), 2.23 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 144.7, 140.9, 140.4, 137.5, 136.7, 135.2, 132.7, 132.5, 130.7, 129.9, 129.4, 128.9, 128.4, 127.6, 127.1, 127.0, 125.9, 125.3, 125.1, 124.4, 120.1, 116.4, 101.4, 21.6. HRMS (ESI-TOF) m/z: [M]+ calcd for C33H25NO2S, 499.1606; found, 499.1611. 4-(3-Phenyl-1-tosyl-1H-indol-2-yl)benzonitrile (3aj). White solid (89 mg, 61% yield), mp 228−229 °C. 1H NMR (400 MHz, CDCl3): δ 8.36 (d, J = 8.0 Hz, 1H), 7.55 (d, J = 8.0 Hz, 2H), 7.42 (d, J = 8.0 Hz, 2H), 7.37 (d, J = 8.0 Hz, 2H), 7.31−7.26 (m, 3H), 7.24−7.22 (m, 3H), 7.08 (d, J = 8.0 Hz, 2H), 7.02−6.99 (m, 2H), 2.30 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 145.2, 137.7, 136.1, 134.7, 132.6, 131.9, 131.2, 130.1, 129.8, 129.6, 128.7, 127.7, 126.9, 126.9, 126.1, 124.8, 120.5, 118.8, 116.6, 112.1, 21.7. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C28H20N2O2SNa, 471.1143; found, 471.1146. Methyl 4-(3-Phenyl-1-tosyl-1H-indol-2-yl)benzoate (3ak). White solid (51 mg, 35% yield), mp 173−174 °C. 1H NMR (400 MHz, CDCl3): δ 8.32 (d, J = 8.0 Hz, 1H), 7.88 (d, J = 8.0 Hz, 2H), 7.39 (d, J = 8.0 Hz, 1H), 7.35 (d, J = 8.0 Hz, 1H), 7.27 (d, J = 8.0 Hz, 2H), 7.24−7.20 (m, 3H), 7.13 (d, J = 8.0 Hz, 3H), 7.01 (d, J = 8.0 Hz, 2H), 6.97 (d, J = 8.0 Hz, 2H), 3.85 (s, 3H), 2.24 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 167.0, 145.0, 137.6, 135.9, 135.7, 135.0, 132.2, 132.1, 130.6, 129.9, 129.9, 129.5, 128.6, 128.5, 127.4, 126.9, 126.0, 125.7, 124.6, 120.3, 116.5, 52.3, 21.7. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C29H23NO4SNa, 504.1245; found, 504.1251. 1-(4-(3-Phenyl-1-tosyl-1H-indol-2-yl)phenyl)ethanone (3am). White solid (87 mg, 62% yield), mp 212−213 °C. 1H NMR (400 MHz, CDCl3): δ 8.35 (d, J = 8.0 Hz, 1H), 7.84 (d, J = 8.0 Hz, 2H), 7.39 (t, J = 8.0 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 7.28 (d, J = 8.0 Hz, 3H), 7.25 (d, J = 8.0 Hz, 1H), 7.21−7.17 (m, 3H), 7.04 (d, J = 8.0 Hz, 2H), 7.00 (d, J = 8.0 Hz, 2H), 2.58 (s, 3H), 2.27 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 197.9, 145.0, 137.6, 136.6, 136.1, 135.7, 134.9, 133.4, 132.2, 130.7, 129.9, 129.5, 129.5, 128.5, 127.4, 127.4, 126.9, 125.8, 124.6, 120.4, 116.5, 26.8, 21.7. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C29H23NO3SNa, 488.1296; found, 488.1289. 2-(Naphthalene-1-yl)-3-phenyl-1-tosyl-1H-indole (3an). White solid (97 mg, 68% yield), mp 206−207 °C. 1H NMR (400 MHz, CDCl3): δ 8.56 (d, J = 8.0 Hz, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.69 (d, J = 8.0 Hz, 1H), 7.54 (t, J = 8.0 Hz, 2H), 7.49−7.44 (m, 2H), 7.41 (d, J = 8.0 Hz, 1H), 7.37 (d, J = 8.0 Hz, 1H), 7.34−7.28 (m, 3H), 7.14 (s, 5H), 7.00 (d, J = 8.0 Hz, 2H), 2.32 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 144.7, 137.2, 135.7, 134.4, 134.1, 130.0, 132.7, 130.9, 129.9, 129.7, 129.4, 129.3, 128.6, 128.2, 128.1, 127.1, 127.0, 126.3, 126.2, 125.7, 125.3, 125.2, 124.5, 124.0, 120.2, 115.8, 21.6. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C31H23NO2SNa, 496.1347; found, 496.1334.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b02728. Characterization data of new compounds, X-ray crystal structures of 3aa′, and 1H and 13C NMR and HRMS spectra (PDF) X-ray crystallographic analysis for compound 3aa′ (CIF) Accession Codes

The CCDC number for 3aa′ is 1579545.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. 328

DOI: 10.1021/acs.joc.7b02728 J. Org. Chem. 2018, 83, 323−329

Article

The Journal of Organic Chemistry ORCID

2003, 5, 2231−2234. (f) Yoon, C. H.; Yoo, K. S.; Yi, S. W.; Mishra, R. K.; Jung, K. W. Org. Lett. 2004, 6, 4037−4039. (16) For a selected review on C−H arylation with organometallics, see: Giri, R.; Thapa, S.; Kafle, A. Adv. Synth. Catal. 2014, 356, 1395− 1411. (17) Arienti, A.; Bigi, F.; Maggi, R.; Marzi, E.; Moggi, P.; Rastelli, M.; Sartori, G.; Tarantola, F. Tetrahedron 1997, 53, 3795−3804. (18) Yanai, H.; Mimura, H.; Kawada, K.; Taguchi, T. Tetrahedron 2007, 63, 2153−2160.

Fanlong Zeng: 0000-0002-4293-5133 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We gratefully acknowledge Dr. Jamie Ferguson (Department of Chemistry, Emory & Henry College) for the constructive discussion and the National Science Foundation of China (no. 21302152), the Key Science and Technology Innovation Team of shaanxi Province (2017KCT-37), and Northwest University for financial support.

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DOI: 10.1021/acs.joc.7b02728 J. Org. Chem. 2018, 83, 323−329