Synthesis of Highly Functionalized Indoles and Indolones via Selec

Julia olefination of the products followed by a Brønsted acid prompted ... indoles, whereas the Julia olefination of 1 yields only mo- ...... of char...
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Note Cite This: J. Org. Chem. 2018, 83, 2467−2472

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Synthesis of Highly Functionalized Indoles and Indolones via Selectivity-Switchable Olefinations Ting-Hui Ding,† Zu-Feng Xiao,† Jian-Ping Qu,*,‡ and Yan-Biao Kang*,† †

Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Jiangsu National Synergetic Innovation Center for Advanced Materials, Nanjing Tech University, Nanjing 211816, China

‡

S Supporting Information *

ABSTRACT: Highly functionalized indoles and indolones were prepared via selectivity-switchable mono- or diolefinations. The Julia olefination of the products followed by a Brønsted acid-prompted cyclization afforded indolones, whereas the indoles were obtained by a sequential Wittig olefination and electrocyclization. This method opens divergent access to highly functionalized nitrogen-containing bicyclic or tricyclic heterocycles. °C affording the electrocyclization products 4 in 52−100% yields (Scheme 1, right column). Alectinib (marketed as Alecensa), first approved in Japan in 2014 and then in the U.S. in 2015, is an orally active inhibitor of anaplastic lymphoma kinase for the treatment of ALKpositive nonsmall cell lung cancer (Figure 1).5 It contains a substituted 4-indolone core structure. The mono-olefination products 2 or 3 can be easily converted to indolones 5 or 6 with TfOH-promoted cyclization. Thus, 2,3-dicarbonyl pyrroles 2 and 3 were used to synthesize the core structure of Alectinib in the presence of triflic acid (Scheme 2). The cyclization of compounds 2 afforded corresponding 4indolones 5a to 5g, whereas the reaction of compounds 3 yielded 7-indolone 6a and 6b. For either 4- or 7-indolone, moderate to excellent yields were obtained. This reaction opens access to highly functionalized indolones. The structure of 5f is confirmed by the X-ray diffraction of the single crystal (CCDC1585936, see SI for details). Starting materials 1 were prepared by the N−O cleaving rearrangement/cyclization reaction catalyzed by Ir-4,4′(Me)2biPy complex (eq 1).4e Various 2,3-dihydroisoxazoles and enones were subjected to the in situ-generated IrCl3-4,4′(Me)2biPy complex at 110 °C in toluene followed by dehydrogenation with DDQ to afford 1. Other catalysts including [RuCl2(p-cymene)]2 and RuCl3-4,4′-(Me)2biPy complex afford moderate yields.4e

S

ubstituted nitrogen-containing heterocycles are core structures widely existing in natural products, bioactive molecules, and pharmaceuticals.1 They are also important building blocks or intermediates in organic photoelectrical materials; consequently, research on the convenient construction of such heterocycles has always attracted chemists.2 Despite numerous methods having been established in this area,3 the construction of multiple-substituted pyrroles and indoles in a one step reaction is more or less a challenge for traditional methods. The N−O bond cleaving cyclization of 2,3-dihydroisoxazole provides practical access to 2,3-dicarbonyl pyrroles (1).4 In further studies, it was found that the selectivity of the olefination of 2,3-dicarbonyl pyrroles could be controlled. The Wittig olefination generates 1,5-dienes that sequentially cyclize to indoles, whereas the Julia olefination of 1 yields only monoene. The Brønsted acid-prompted cyclization of the Julia olefination products affords multiple substituted 4-indolones. In this work, we report this selective-switchable olefination of 2,3dicarbonyl pyrroles and its application in the synthesis of highly functionalized indoles and indolones. First, 2,3-dicarbonyl pyrroles 1 were subjected to the Julia olefination conditions to afford olefination products 2 and 3 in up to 99% yields (Scheme 1, left column). It worth mentioning that when the R3 substituent is an aryl group the olefination occurs on the ketone on the 3-position of pyrrole, whereas when the R3 substituent is a methyl group the olefination occurs on the ketone on the 2-position of pyrrole. The reason for this is unclear. The structure of mono-olefination product 2a was confirmed by X-ray diffraction of the single crystal (CCDC1585935, see SI for details). Next, pyrroles 1 were subjected to the standard Wittig reaction conditions using PPh3CH3Br as the olefination reagent in the presence of sodium hydride at room temperature. After complete consumption of 1, the reaction mixture was then stirred at 80 © 2018 American Chemical Society

Received: December 14, 2017 Published: January 29, 2018 2467

DOI: 10.1021/acs.joc.7b03158 J. Org. Chem. 2018, 83, 2467−2472

Note

The Journal of Organic Chemistry Scheme 1. Selective-Switchable Olefinationa

Scheme 2. Synthesis of Indolonesa

a

Conditions: 2 or 3 (0.25 mmol), TfOH (0.5 mL), isolated yields.

Scheme 3. Proposed Mechanism

a Conditions A for Julia olefination: 1 (0.5 mmol), LiHMDS (4 mmol), 5-(methylsulfonyl)-1-phenyl-1H-tetrazole (2 mmol), THF (5 mL). Conditions B for Wittig olefination: 1 (0.25 mmol), PPh3CH3Br (1.0 mmol), NaH (2.0 mmol), THF (2.5 mL); brsm refers to the yield based on the recovery of starting materials. bDioxane instead of THF, 100 °C.

group chelation-accelerated nucleophilic addition of carbanion to the carbonyl group. This hypothesis can be proven by the fact that KHMDS is much less reactive compared to that of LiHMDS as a base. The [2 + 2] cycloaddition does not need the participation of a neighboring carbonyl, which enables the Wittig olefination of both carbonyl groups. The Julia olefination stops at the mono-olefin stage due to no acceleration of chelating groups. The mechanistic insight is still under investigation. In conclusion, divergent access to substituted indoles and pyrroles was developed. An iridium-catalyzed N−O cleaving rearrangement/cyclization of isoxazolines and alkenes afforded multiple substituted pyrroles. A tandem Wittig olefinationelectrocyclization of the cyclization product afforded substituted indoles. Julia olefination of the cyclization product could occur selectively on the carbonyl group. The following

Figure 1. Representative 4-indolone-containing compounds.

A proposed mechanism for explaining the mono- and diolefination is demonstrated (Scheme 3). The Wittig olefination passes through a [2 + 2] cycloaddition, whereas the Julia olefination takes place via a neighboring carbonyl 2468

DOI: 10.1021/acs.joc.7b03158 J. Org. Chem. 2018, 83, 2467−2472

Note

The Journal of Organic Chemistry

128.3, 128.1, 125.3, 35.0, 21.4. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H26NO2 456.1964; found 456.1969. (4-(4-Fluorophenyl)-1-methyl-5-phenyl-1H-pyrrole-2,3-diyl)bis(phenylmethanone) (1c). This compound was prepared according to general procedure 1 and purified by silica gel column (PE/EA 50:1− 10:1): 160.8 mg, 69%, yellow solid, mp 154−156 °C. 1H NMR (400 MHz, CDCl3) δ 7.42−7.38 (m, 5H), 7.36−7.33 (m, 1H), 7.31−7.25 (m, 5H), 7.16−7.08 (m, 6H), 6.79−6.75 (m, 2H), 3.80 (s, 3H). 13 C{1H} NMR (100 MHz, CDCl3) δ 193.5, 188.5, 163.2, 160.8, 140.2, 140.1, 138.9, 132.7, 132.7, 132.6, 131.7, 131.4, 130.6, 130.0, 129.7 (two peaks), 129.1 (two peaks), 128.9, 128.3, 128.2, 124.2, 115.0, 114.9, 35.0. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C31H23FNO2 460.1713; found 460.1718. (4-(3,4-Dichlorophenyl)-1-methyl-5-phenyl-1H-pyrrole-2,3-diyl)bis(phenylmethanone) (1d). This compound was prepared according to general procedure 1 and purified by silica gel column (PE/EA 50:1−10:1): 168.4 mg, 66%, yellow solid, mp 215−217 °C. 1H NMR (400 MHz, CDCl3) δ 7.43−7.37 (m, 6H), 7.35−7.29 (m, 4H), 7.27 (m, 1H), 7.24 (m, 1H), 7.17−7.10 (m, 5H), 6.94 (dd, J = 8.4, 2.0 Hz, 1H), 3.79 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 193.5, 188.7, 140.3, 139.2, 134.2, 133.2, 133.0, 133.0, 132.3, 132.2, 131.6, 131.3, 130.8, 130.3, 130.1, 130.0, 129.7, 129.6, 129.4, 129.3, 128.6, 128.5, 122.9, 35.2. HRMS (ESI-TOF) m/z: [M + H] + calcd for C31H22Cl2NO2 510.1028; found 510.1025. (4-(4-Chlorophenyl)-1-methyl-5-phenyl-1H-pyrrole-2,3-diyl)bis(phenylmethanone) (1e). This compound was prepared according to general procedure 1 and purified by silica gel column (PE/EA 50:1− 10:1): 180.9 mg, 76%, yellow solid. mp 124−126 °C. 1H NMR (400 MHz, CDCl3) δ 7.41−7.27 (m, 11H), 7.16−7.06 (m, 8H), 3.80 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 192.3, 188.3, 140.2, 138.9, 138.4, 133.5, 132.7, 131.4, 131.0, 130.6, 130.4, 129.7, 129.6, 129.0, 128.8, 128.4, 128.4, 128.0, 126.9, 125.2, 34.9. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C31H23NO2Cl 476.1417; found 476.1422. (4-(4-Bromophenyl)-1-methyl-5-phenyl-1H-pyrrole-2,3-diyl)bis(phenylmethanone) (1f). This compound was prepared according to general procedure 1 and purified by silica gel column (PE/EA 50:1− 10:1): 171.7 mg, 66%, yellow solid, mp 143−145 °C. 1H NMR (400 MHz, CDCl3) δ 7.40−7.29 (m, 10H), 7.25 (m, 1H), 7.21−7.19 (m, 2H), 7.16−7.09 (m, 4H), 7.0 (m, 2H), 3.8 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 193.6, 188.5, 140.2, 140.1, 138.9, 132.7, 132.7, 131.9, 131.5, 131.2, 130.5, 129.8, 129.7, 129.2, 129.1, 129.1, 128.4, 128.3, 121.2, 35.0. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C31H23BrNO2 520.0912; found 520.0919. (5-(3,4-Dichlorophenyl)-1-methyl-4-phenyl-1H-pyrrole-2,3-diyl)bis(phenylmethanone) (1g). This compound was prepared according to general procedure 1 and purified by silica gel column (PE/EA 50:1−10:1): 127.6 mg, 50%, yellow solid, mp 215−217 °C. 1H NMR (400 MHz, CDCl3) δ 7.61−7.39 (m, 12H), 7.32−7.24 (m, 6H), 3.96 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 193.2, 188.5, 139.9, 139.9, 135.9, 133.4, 133.1, 133.0, 133.0, 132.8, 132.6, 132.2, 131.0, 130.9, 130.8, 130.8, 129.9, 129.6, 129.1, 128.4, 128.2, 128.2, 127.3, 125.8, 35.0. HRMS (ESI-TOF) m/z: [M + H] + calcd for C31H22Cl2NO2 510.1028; found 510.1028. 1-(2-Benzoyl-4-(4-fluorophenyl)-1-methyl-5-phenyl-1H-pyrrol-3yl)ethan-1-one (1h). This compound was prepared according to general procedure 1 and purified by silica gel column (PE/EA 50:1− 10:1): 65.6 mg, 33%, yellow solid, mp 193−195 °C. 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 7.2 Hz, 2H), 7.58 (t, J = 7.2 Hz, 1H), 7.47 (t, J = 8.0 Hz, 2H), 7.34−7.32 (m, 3H), 7.21−7.18 (m, 2H), 7.15− 7.12 (m, 2H), 6.92 (t, J = 8.4 Hz, 2H), 3.57 (s, 3H), 1.82 (s, 3H). 13 C{1H} NMR (100 MHz, CDCl3) δ 197.0, 190.1, 163.5, 161.0, 139.1, 136.7, 133.6, 132.8, 132.7, 132.3, 131.3, 130.5 (three peaks), 129.7, 128.9, 128.8 (two peaks), 122.4, 115.4, 115.2, 34.1, 31.3. HRMS (ESITOF) m/z: [M + H]+ calcd for C26H21FNO2 398.1556; found 398.1561. 1-(2-Benzoyl-1-methyl-4,5-diphenyl-1H-pyrrol-3-yl)ethan-1-one (1i). This compound was prepared according to general procedure 1 and purified by silica gel column (PE/EA 50:1−10:1): 106.2 mg, 56%, yellow solid, mp 189−192 °C. 1H NMR (400 MHz, CDCl3) δ 7.92− 7.90 (m, 2H), 7.58−7.55 (m, 1H), 7.48−7.44 (m, 2H), 7.32−7.31 (m,

cyclization prompted by Brønsted acid afforded multiple substituted indolones.

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EXPERIMENTAL SECTION

General Information. Solvents were predried over activated MS 4 Å and heated to reflux over sodium (for toluene and THF) or calcium hydride (for CH2Cl2) under a nitrogen atmosphere and collected by distillation. 1H NMR (400 MHz) and 13C{1H} NMR (100 MHz) spectra were recorded on a Bruker spectrometer. Chemical shifts are reported in δ units relative to TMS (1H δ = 0; CDCl3, 1H δ = 7.26, 13C δ = 77.36). General Procedure 1 for the Preparation of Pyrroles via IrCatalyzed N−O Cleaving Cyclization of Isoxaolines with Alkenes.4e IrCl3·H2O (7.4 mg, 0.025 mmol) and 6,6′-dimethyl-2,2′bipyridine (18.4 mg, 0.1 mmol) in 1 mL of dry MeOH were stirred at 75 °C for 1 day. MeOH was evaporated, and the residue was diluted with 1 mL of dry toluene. Then, K2CO3 (69 mg, 0.5 mmol), pivalic acid (7.4 mg, 0.075 mmol), and 18 μL of deionized H2O were added sequentially, stirred at 110 °C for 5 min, and cooled to rt; then, 2,3dihydroisoxazoles (0.5 mmol), alkenes (0.5 mmol) and another 1 mL of dry toluene were added, and the reaction was stirred at 110 °C and monitored by TLC. The reaction mixture was cooled to rt and DDQ (2.0 equiv) was added and stirred at 110 °C and monitored by TLC. The reaction mixture was cooled to rt, filtered through a thin silica gel pad, and washed with EA. The filtrate was concentrated, and the residue was purified by flash chromatography. General Procedure 2 for Julia Olefination. A mixture of pyrroles from general procedure 1 (0.5 mmol) and 5-(methylsulfonyl)1-phenyl-1H-tetrazole (2 mmol) in dry THF was stirred at rt for 10 min. LiHMDS (4 mmol) was added dropwise. The reaction was monitor by TLC and quenched by filtration through a pad of silica gel. The filtrate was concentrated under reduced pressure, and the residue was purified by flash chromatography. General Procedure 3 for the Sequential Wittig Olefination/ Electrocyclization. Methyltriphenylphosphonium bromide (1.0 mmol) was added to a suspension of NaH (2.0 mmol) in dry THF under an argon atmosphere at 0 °C. The resulting reaction mixture was stirred and allowed to warm to room temperature. Pyrroles prepared above (0.25 mmol) were added to the reaction, and the reaction mixture continued to stir until the starting materials disappeared. Then, water was added to the mixture. The reaction mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by flash chromatography. General Procedure 4 for the Julia Olefination/Cyclization. The Julia olefination products (0.25 mmol) were added to a solution of TfOH (0.5 mL) and heated at 80 °C until disappearance of the starting materials. Ice water was added dropwise to the reaction mixture. The reaction mixture was extracted with ethyl acetate.The organic layer was washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by flash chromatography. (1-Methyl-4,5-diphenyl-1H-pyrrole-2,3-diyl)bis(phenylmethanone) (1a). This compound was prepared according to general procedure 1 and purified by silica gel column (PE/EA 50:1−10:1): 189.9 mg, 86%, yellow solid, mp 157−159 °C. 1H NMR (400 MHz, CDCl3) δ 7.43−7.26 (m, 11H), 7.15−7.05 (m, 9H), 3.81 (s, 3H). 13 C{1H} NMR (100 MHz, CDCl3) δ 193.6, 188.5, 140.2, 140.1, 138.8, 133.6, 132.5 (two peaks), 131.5, 131.4, 131.0, 130.7, 130.1, 129.6, 129.1, 128.9, 128.8, 128.3, 128.1, 127.9, 126.8, 125.2, 34.9. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C31H24NO2 442.1807; found 442.1811. (1-Methyl-5-phenyl-4-(p-tolyl)-1H-pyrrole-2,3-diyl)bis(phenylmethanone) (1b). This compound was prepared according to general procedure 1 and purified by silica gel column (PE/EA 50:1−10:1): 88.8 mg, 39%, yellow solid, mp 145−146 °C. 1H NMR (400 MHz, CDCl3) δ 7.41−7.28 (m, 10H), 7.15−7.07 (m, 5H), 7.01−6.99 (m, 2H), 6.89−6.87 (m, 2H), 3.80 (s, 3H), 2.18 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 193.8, 188.4, 140.3, 140.2, 138.9, 136.3, 132.5, 131.5, 130.9, 130.8, 130.5, 130.3, 129.7, 129.1, 128.9, 128.8, 128.7, 2469

DOI: 10.1021/acs.joc.7b03158 J. Org. Chem. 2018, 83, 2467−2472

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The Journal of Organic Chemistry

128.7, 128.4, 128.2, 127.9, 126.9, 123.4, 122.9, 120.7, 114.9 (two peaks), 33.5. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H25FNO 458.1920; found 458.1923. (4-(3,4-Dichlorophenyl)-1-methyl-5-phenyl-2-(1-phenylvinyl)-1Hpyrrol-3-yl)(phenyl)methanone (2d). This compound was prepared according to general procedure 2 and purified by silica gel column (PE/EA 50:1−10:1): 508.44 mg, 46% (starting material was recovered in 36%, 93.8 mg), yellow foam, mp 147−149 °C. 1H NMR (400 MHz, CDCl3) δ 7.62 (d, J = 8.0 Hz, 2H), 7.34−7.19 (m, 11H), 7.13−7.09 (m, 3H), 7.01 (d, J = 8.4 Hz, 2H), 6.84 (d, J = 8.0 Hz, 2H), 5.75 (s, 1H), 5.40(s, 1H), 3.17 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 194.2, 139.8, 139.5, 139.1, 136.8, 135.4, 133.2, 132.3, 131.6, 131.5, 131.3, 130.0, 129.8, 129.7, 128.9, 128.5, 128.4, 128.0, 126.8, 123.3, 121.5, 120.9, 33.5. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H24Cl2NO 508.1235; found 508.1243. (4-(4-Chlorophenyl)-1-methyl-5-phenyl-2-(1-phenylvinyl)-1H-pyrrol-3-yl)(phenyl)methanone (2e). This compound was prepared according to general procedure 2 and purified by silica gel column (PE/EA 50:1−10:1): 234.6 mg, 99%, yellow foam, mp 126−128 °C. 1 H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 7.6 Hz, 2H), 7.35−7.24 (m, 11H), 7.16−7.12 (m 2H), 7.00−6.96 (m, 4H), 5.78 (s, 1H), 5.45 (s, 1H), 3.20 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 194.5, 140.0, 139.5, 139.3, 136.5, 133.7, 132.9, 132.4, 131.9, 131.8, 131.6, 129.9,128.9, 128.8, 128.4, 128.3, 128.1, 128.0, 126.9, 123.5, 122.7, 120.9, 33.6. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H25ClNO 474.1625; found 474.1620. (4-(4-Bromophenyl)-1-methyl-5-phenyl-2-(1-phenylvinyl)-1H-pyrrol-3-yl)(phenyl)methanone (2f). This compound was prepared according to general procedure 2 and purified by silica gel column (PE/EA 50:1−10:1): 170.2 mg, 68% (starting material was recovered in 26%, 69.2 mg), yellow foam, mp 132−134 °C. 1H NMR (400 MHz, CDCl3) δ 7.68 (dd, J = 8.0, 1.2 Hz, 2H), 7.35−7.28 (m, 9H), 7.25− 7.23 (m, 2H), 7.16−7.11 (m, 4H), 6.95−6.91 (m, 2H), 5.77 (d, J = 1.2 Hz, 1H),5.44 (d, J = 1.2 Hz, 1H), 3.20 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 194.5, 140.1, 139.6, 139.4, 136.5, 134.2, 132.9, 132.4, 132.3, 131.8, 131.6, 131.1, 129.9, 129.0, 128.9, 128.4, 128.4, 128.1, 127.0, 123.5, 122.7, 120.9, 120.1, 33.6. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H25BrNO 518.1120; found 518.1117. (5-(3,4-Dichlorophenyl)-1-methyl-4-phenyl-2-(1-phenylvinyl)-1Hpyrrol-3-yl)(phenyl)methanone (2g). This compound was prepared according to general procedure 2 and purified by silica gel column (PE/EA 50:1−10:1): 163.3 mg, 64% (starting material was recovered in 4%,10.2 mg), yellow foam, mp 205−207 °C. 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 7.2 Hz, 2H), 7.40−7.25 (m, 8H), 7.14−7.10 (t, J = 7.6 Hz, 2H), 7.05−7.01 (m, 6H), 5.81 (s, 1H), 5.48 (s, 1H), 3.22 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 194.3, 139.9, 139.3, 139.1, 136.9, 134.4, 133.0, 132.7, 132.3, 132.2, 132.1, 131.0, 130.7, 130.6, 129.9, 129.8, 128.9, 128.4, 128.1, 127.9, 126.9, 126.4, 124.7, 123.9, 121.1, 33.6. HRMS (ESI-TOF) m/z: [M + H] + calcd for C32H24Cl2NO 508.1229; found 508.1223. (4-(4-Fluorophenyl)-1-methyl-5-phenyl-3-(prop-1-en-2-yl)-1Hpyrrol-2-yl)(phenyl)methanone (3a). This compound was prepared according to general procedure 2 and purified by silica gel column (PE/EA 50:1−10:1): 164.1 mg, 82%, yellow foam, mp 167−169 °C. 1 H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 7.2 Hz, 2H), 7.50 (t, J = 7.2 Hz, 1H), 7.40−7.33 (m, 5H), 7.26−7.22 (m, 2H), 7.07−7.03 (m, 2H), 6.84 (t, J = 8.4 Hz, 2H),4.69 (s, 1H), 4.66 (s, 1H), 3.70 (s, 3H), 1.47 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 189.8, 162.9, 160.4, 140.9, 138.7, 138.0, 133.7, 132.3, 131.9, 131.8, 131.4 (two peaks), 129.8, 128.6, 128.5, 128.1, 121.5, 119.9, 115.0, 114.8, 34.1, 24.2. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C27H23FNO 396.1764; found 396.1761. (1-Methyl-4,5-diphenyl-3-(prop-1-en-2-yl)-1H-pyrrol-2-yl)(phenyl)methanone (3b). This compound was prepared according to general procedure 2 and purified by silica gel column (PE/EA 50:1− 10:1): 121.8 mg, 64%, yellow foam, mp 177−179 °C. 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 8 Hz, 2H), 7.50 (t, J = 8.0 Hz, 1H), 7.40− 7.32 (m, 6H), 7.24 (m, 1H) 7.16−7.09 (m, 5H), 4.68 (s, 1H), 4.66 (s, 1H), 3.71 (s, 3H), 1.47 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 189.9, 141.0, 138.9, 138.0, 135.5, 133.8, 132.2, 131.6, 131.4, 130.4,

3H), 7.23−7.20 (m, 5H), 7.18−7.15 (m, 2H), 3.56 (s, 3H), 1.82 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 197.1, 190.3, 139.2, 136.4, 134.6, 133.4, 132.3, 131.3, 131.1, 130.7, 129.7, 129.6, 128.8, 128.7, 128.3, 127.3, 123.5, 34.0, 31.1. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C26H22NO2 380.1651; found 380.1656. (1-Methyl-5-phenyl-4-(o-tolyl)-1H-pyrrole-2,3-diyl)bis(phenylmethanone) (1j). This compound was prepared according to general procedure 1 and purified by silica gel column (PE/EA 50:1−10:1): 97.9 mg, 43%, yellow solid, mp 192−194 °C. 1H NMR (400 MHz, CDCl3) δ 7.36−7.34 (m, 2H), 7.30−7.21 (m, 7H), 7.17−7.15 (m, 2H), 7.10−6.98 (m, 7H), 6.90−6.89 (m, 1H), 3.81 (s, 3H), 1.92 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 193.0, 188.4, 140.4, 140.3, 139.0, 137.7, 133.2, 132.7, 132.5, 132.2, 131.8, 130.8, 130.7, 130.4, 129.7, 129.6, 128.9, 128.7, 128.7, 128.3, 128.0, 127.7, 125.1, 124.9, 35.3, 20.7. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H26NO2 456.1964; found 456.1967. (4-(3-Fluorophenyl)-1-methyl-5-phenyl-1H-pyrrole-2,3-diyl)bis(phenylmethanone) (1k). This compound was prepared according to general procedure 1 and purified by silica gel column (PE/EA 50:1− 10:1): 181.5 mg, 79%, yellow solid, mp 174−176 °C. 1H NMR (400 MHz, CDCl3) δ 7.42−7.29 (m, 11H), 7.16−7.10 (m, 4H), 7.05−6.99 (m, 1H), 6.88−6.82 (m, 2H), 6.78−6.73 (m, 1H), 3.80 (s, 3H). 13 C{1H} NMR (100 MHz, CDCl3) δ 193.4, 188.5, 163.6, 161.2, 140.0 (two peaks), 138.8, 135.9 (two peaks), 132.7 (two peaks), 131.7, 131.4, 130.4, 129.8, 129.6, 129.4, 129.3, 129.2, 129.1, 128.9, 128.3, 128.2, 126.9 (two peaks), 123.9 (two peaks), 118.0 (two peaks), 113.9 (two peaks), 34.9. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C31H23FNO2 460.1713; found 460.1713. (4-(4-Methoxyphenyl)-1-methyl-5-phenyl-1H-pyrrole-2,3-diyl)bis(phenylmethanone) (1l). This compound was prepared according to general procedure 1 and purified by silica gel column (PE/EA 50:1− 10:1): 146.2 mg, 62%, yellow solid, mp 146−149 °C. 1H NMR (400 MHz, CDCl3) δ 7.41−7.35 (m, 6H), 7.33−7.30 (m, 3H), 7.27−7.25 (m,2H), 7.15−7.04 (m,6H), 6.64−6.61 (m,2H), 3.81 (s, 3H), 3.68 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 193.8, 188.4, 158.5, 140.3, 140.2, 138.9, 132.5, 132.2, 131.5, 131.5, 130.8, 130.3, 129.7, 129.1, 128.8, 128.3, 128.1, 125.9, 124.9, 113.4, 55.3, 35.0. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H26NO3 472.1907; found 472.1909. (1-Methyl-4,5-diphenyl-2-(1-phenylvinyl)-1H-pyrrol-3-yl)(phenyl)methanone (2a). This compound was prepared according to general procedure 2 and purified by silica gel column (PE/EA 50:1−10:1): 141 mg, 64% (starting material was recovered in 30%, 66 mg), yellow foam, mp 147−150 °C. 1H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 7.2 Hz, 2H), 7.35−7.24 (m, 11H), 7.12 (t, J = 7.6 Hz, 2H), 7.06 (m, 2H), 7.00−6.94 (m, 3H), 5.80 (s, 1H), 5.48 (s, 1H), 3.21 (s, 3H). 13 C{1H} NMR (100 MHz, CDCl3) δ 194.6, 140.2, 139.6, 139.4, 136.3, 135.1, 132.5, 132.1, 132.1, 131.7, 130.7, 129.9, 128.9, 128.6, 128.3, 128.1, 127.9, 127.8, 126.9, 125.9, 123.8, 123.7, 120.7, 33.5. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H26NO 440.2014; found 440.2018. (1-Methyl-5-phenyl-2-(1-phenylvinyl)-4-(p-tolyl)-1H-pyrrol-3-yl)(phenyl)methanone (2b). This compound was prepared according to general procedure 2 and purified by silica gel column (PE/EA 50:1− 10:1): 277.5 mg, 76%, yellow foam, mp 152−154 °C. 1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 7.6 Hz, 2H), 7.32−7.27 (m, 10H), 7.14− 7.10 (m, 3H), 6.95 (d, J = 8.0 Hz, 2H), 6.80 (d, J = 7.6 Hz, 2H), 5.75 (s, 1H), 5.44 (s, 1H), 3.18 (s, 3H), 2.15 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 194.9, 140.4, 139.8, 139.6, 136.2, 135.5, 132.6, 132.4, 132.2, 132.1, 131.8, 130.6, 130.0, 129.0, 128.8, 128.4, 128.1, 128.0, 127.1, 124.0, 123.9, 120.8, 33.7, 21.5. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C33H28NO 454.2171; found 454.2170. (4-(4-Fluorophenyl)-1-methyl-5-phenyl-2-(1-phenylvinyl)-1H-pyrrol-3-yl)(phenyl)methanone (2c). This compound was prepared according to general procedure 2 and purified by silica gel column (PE/EA 50:1−10:1): 226.5 mg, 99%, yellow foam, mp 175−177 °C. 1 H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 7.2 Hz, 2H), 7.34−7.25 (m, 11H), 7.13 (t, J = 7.6 Hz, 2H), 7.04−7.00 (m, 2H), 6.71−6.67 (m, 2H), 5.78 (s, 1H), 5.45 (s, 1H), 3.21 (s, 1H). 13C{1H} NMR (100 MHz, CDCl3) δ 194.5, 162.7, 160.2, 140.5, 140.1, 139.6, 139.4, 136.4, 132.7, 132.2 (three peaks), 131.9, 131.1 (two peaks), 129.9, 128.9, 2470

DOI: 10.1021/acs.joc.7b03158 J. Org. Chem. 2018, 83, 2467−2472

Note

The Journal of Organic Chemistry

1-Methyl-2,4,7-triphenyl-3-(o-tolyl)-1H-indol (4g). This compound was prepared according to general procedure 3 and purified by silica gel column (PE/EA 50:1−10:1): 94.4 mg, 84%, white solid, mp 179−181 °C. 1H NMR (400 MHz, CDCl3) δ 7.66−7.65 (m, 2H), 7.49 (t, J = 7.6 Hz, 2H), 7.44−7.40 (m, 1H), 7.21−7.20 (m, 4H), 7.14−7.11 (m, 3H), 7.05−7.04 (m, 2H), 6.99−6.96 (m, 1H), 6.90 (t, J = 7.6 Hz, 2H), 6.85−6.84 (m, 1H), 6.78−6.77 (m, 1H), 6.72 (t, J = 7.2 Hz, 2H), 3.22 (s, 3H), 1.77 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 141.4, 141.2, 140.1, 137.7, 136.5, 136.0, 135.7, 132.5, 132.3, 131.1, 130.3, 129.6, 129.1, 128.2, 127.9, 127.4, 126.8, 126.4, 126.2, 126.0, 125.2, 125.0, 122.2, 116.1, 36.3, 20.7. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C34H28N 450.2222; found 450.2213. 3-(3-Fluorophenyl)-1-methyl-2,4,7-triphenyl-1H-indol (4h). This compound was prepared according to general procedure 3 and purified by silica gel column (PE/EA 50:1−10:1): 121 mg, quant, white solid, mp 199−202 °C. 1H NMR (400 MHz, CDCl3) δ 7.62−7.60 (m, 2H), 7.49−7.45 (m, 2H), 7.43−7.41 (m, 1H), 7.27−7.25 (m, 2H), 7.23− 7.21 (m, 1H), 7.17−7.15 (m, 3H), 7.10−6.99 (m, 6H), 6.77−6.69 (m, 1H), 6.59−6.54 (m, 1H), 6.49−6.47 (m, 1H), 6.41−6.38 (m, 1H), 3.17 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 163.4, 161.0, 141.4, 141.1, 140.7, 138.5 (two peaks), 135.9, 135.2, 131.9, 131.6, 130.3, 129.5, 128.4, 128.3 (three peaks), 127.5, 127.3, 127.0 (three peaks), 126.4 (two peaks), 125.5, 125.4, 122.4, 118.1, 117.9,115.9 (two peaks), 112.2, 111.9, 35.9. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C33H25FN 454.1971; found 454.1975. 3-(4-Methoxyphenyl)-1-methyl-2,4,7-triphenyl-1H-indol (4i). This compound was prepared according to general procedure 3 and purified by silica gel column (PE/EA 50:1−10:1): 121.4 mg, quant, white solid, mp 135−138 °C. 1H NMR (400 MHz, CDCl3) δ 7.62−7.60 (m, 2H), 7.47 (t, J = 7.2 Hz, 2H), 7.42−7.38 (m, 1H), 7.25−7.13 (m, 7H), 7.07−7.01 (m, 3H), 6.98−6.94 (m, 2H), 6.60 (d, J = 7.6 Hz, 2H), 6.35 (d, J = 8.4 Hz, 2H), 3.67 (s, 3H), 3.17 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 157.4, 141.3, 141.2, 140.8, 136.0, 135.5, 132.4, 132.0, 131.7, 130.3, 129.8, 128.4, 128.3, 128.2, 127.9, 127.4, 127.1, 126.2, 126.0, 125.8, 125.1, 122.2, 116.7, 112.8, 55.5, 35.9. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C34H28NO 466.2171; found 466.2167. 1,9-Dimethyl-2,3,9-triphenyl-1,9-dihydro-4H-benzo[f ]indol-4one (5a). This compound was prepared according to general procedure 4 and purified by silica gel column (PE/EA 50:1−10:1): 86.9 mg, 80%, brown solid, mp 234−236 °C. 1H NMR (400 MHz, CDCl3) δ 8.29 (dd, J = 8.0, 1.6 Hz, 1H), 7.41−7.31 (m, 8H), 7.29− 7.25 (m, 4H), 7.23−7.17 (m, 3H), 7.14−7.12 (m, 2H), 7.0 (dd, J = 8, 1.2 Hz, 1H), 3.02 (s, 3H), 2.17 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 180.3, 148.8, 146.8, 144.0, 134.8, 134.4, 131.9, 131.4, 131.4, 131.2, 131.1, 129.1, 128.2, 127.9, 127.5, 127.2, 127.1, 126.7, 126.5, 126.1, 121.7, 116.5, 45.1, 33.2, 27.8. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H26NO 440.2014; found 440.2020. 1,9-Dimethyl-2,9-diphenyl-3-(p-tolyl)-1,9-dihydro-4H-benzo[f ]indol-4-one (5b). This compound was prepared according to general procedure 4 and purified by silica gel column (PE/EA 50:1−10:1): 109.4 mg, 96%, brown solid, mp 241−244 °C. 1H NMR (400 MHz, CDCl3) δ 8.30 (d, J = 7.6 Hz, 1H), 7.39−7.30 (m, 8H), 7.28−7.18 (m, 4H), 7.16−7.13 (m, 1H), 7.09−7.02 (m, 4H), 3.01 (s, 3H), 2.31 (s, 3H), 2.16 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 180.6, 149.1, 147.0, 144 3, 137.9, 135.8, 135.2, 134.9, 132.1, 131.7 (three peaks), 131.5 (two peaks), 131.4, 131.2, 129.3 (two peaks), 128.5, 128.3, 128.1, 127.8, 127.5, 127.3, 126.9, 126.7, 126.3, 121.9 (two peaks), 116.8 (two peaks), 45.4, 33.5, 28.1, 21.6. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C33H28NO 454.2171; found 454.2172. 3-(4-Fluorophenyl)-1,9-dimethyl-2,9-diphenyl-1,9-dihydro-4Hbenzo[f ]indol-4-one (5c). This compound was prepared according to general procedure 4 and purified by silica gel column (PE/EA 50:1− 10:1): 68.6 mg, 60%, brown solid, mp 237−239 °C. 1H NMR (400 MHz, CDCl3) δ 8.29 (d, J = 8.0 Hz, 1H), 7.39−7.36 (m, 12H), 7.13− 7.09 (m, 3H), 6.92 (t, J = 8.8 Hz, 2H), 3.02 (s, 3H), 2.16 (s, 3H). 13 C{1H} NMR (100 MHz, CDCl3) δ 180.7, 163.1, 160.7, 149.2, 147.2, 144.2, 135.2, 132.9 (two peaks), 132.3, 131.7, 131.6, 131.4 (two peaks), 130.6 (two peaks), 129.4, 128.6 (three peaks), 128.3, 127.8, 127.4, 126.9, 126.8, 120.9, 116.7, 114.5, 114.3, 45.4, 33.5, 28.1. HRMS

129.8, 128.6, 128.6, 128.4, 128.1, 128.0, 126.3, 122.6, 119.7, 34.1, 24.3. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C27H24NO 378.1858; found 378.1854. 1-Methyl-2,3,4,7-tetraphenyl-1H-indol (4a). This compound was prepared according to general procedure 3 and purified by silica gel column (PE/EA 50:1−10:1): 78.6 mg, 72%, white solid, mp 182−184 °C. 1H NMR (400 MHz, CDCl3) δ 7.63−7.61 (m, 2H), 7.48 (t, J = 7.6 Hz, 2H), 7.41 (t, J = 7.6 Hz, 1H), 7.24−7.21 (m, 4H), 7.19−7.16 (m, 3H), 7.08−7.06 (m, 2H), 7.03−6.99 (m, 1H), 6.95−6.91 (m, 2H), 6.88−6.85 (m, 1H), 6.77 (t, J = 7.6 Hz, 2H), 6.71−6.69 (m, 2H), 3.18 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 141.4, 141.3, 140.7, 136.0, 136.0, 135.4, 132.3, 131.7, 131.2, 130.3, 129.7, 128.3, 128.2, 128.0, 127.4, 127.2, 127.1, 126.3, 126.1, 125.6, 125.2, 125.1, 122.4, 117.1, 35.9. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C33H26N 436.2065; found 436.2064. 1-Methyl-2,4,7-triphenyl-3-(p-tolyl)-1H-indol (4b). This compound was prepared according to general procedure 3 and purified by silica gel column (PE/EA 50:1−10:1): 92.4 mg, 84%, white solid, mp 219−222 °C. 1H NMR (400 MHz, CDCl3) δ 7.63−7.61 (m, 2H), 7.47 (t, J = 7.2 Hz, 2H), 7.43−7.39 (m, 1H), 7.26 (m, 2H), 7.21−7.19 (m, 3H), 7.15−7.13 (m, 1H), 7.06−7.00 (m, 3H), 6.93 (t, J = 7.6 Hz, 2H), 6.58 (s, 4H), 3.17 (s, 3H), 2.16 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 141.4, 141.1, 140.9, 136.0, 135.5, 134.5, 132.9, 132.4, 131.7, 131.0, 130.3, 129.7, 128.3, 128.2, 127.9, 127.8, 127.4, 127.1, 126.2, 125.9, 125.8, 125.1, 122.3, 117.1, 35.9, 21.3. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C34H28N 450.2222; found 450.2215. 3-(4-Fluorophenyl)-1-methyl-2,4,7-triphenyl-1H-indol (4c). This compound was prepared according to general procedure 3 and purified by silica gel column (PE/EA 50:1−10:1): 90.6 mg, 80%, white solid, mp 239−241 °C. 1H NMR (400 MHz, CDCl3) δ 7.62−7.60 (m, 2H), 7.48 (t, J = 7.6 Hz, 2H), 7.43−7.40 (m, 1H), 7.28−7.26 (m, 2H), 7.22−7.14 (m, 5H), 7.07−7.05 (m, 3H), 7.00−6.96 (m, 2H), 6.64 (t, J = 7.6 Hz, 2H), 6.50−6.46 (m, 2H), 3.17 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 141.4, 141.1, 140.6, 135.9, 135.3, 132.5, 132.4, 131.6, 131.2, 130.3, 129.7, 128.4, 128.2, 128.1, 127.5, 127.3, 126.3, 126.3, 125.7, 125.3, 122.3, 115.9, 114.1, 113.9, 35.9. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C33H25FN 454.1971; found 454.1964. 3-(3,4-Dichlorophenyl)-1-methyl-2,4,7-1H-indol (4d). This compound was prepared according to general procedure 3 and purified by silica gel column (PE/EA 50:1−10:1): 77.4 mg, 52%, white solid, mp 197−200 °C. 1H NMR (400 MHz, CDCl3) δ 7.61−7.60 (m, 2H), 7.49 (t, J = 6.8 Hz, 2H), 7.44−7.41 (m, 1H), 7.30 (m, 3H), 7.24−7.05 (m, 9H), 6.89−6.87 (m, 1H), 6.77 (m, 1H), 6.57−6.55 (m, 1H), 3.18 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 141.5, 141.0, 140.5, 136.5, 135.8, 135.1, 133.3, 131.6, 131.5, 131.0, 130.3, 130.2, 129.5, 129.2, 128.9, 128.6, 128.5, 128.2, 127.6, 127.5, 126.7, 126.5, 125.5, 125.5, 122.3, 114.6, 35.8. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C33H24Cl2N 504.1286; found 504.1277. 3-(4-Chlorophenyl)-1-methyl-2,4,7-triphenyl-1H-indol (4e). This compound was prepared according to general procedure 3 and purified by silica gel column (PE/EA 50:1−10:1): 79.7 mg, 68%, white solid, mp 262−264 °C. 1H NMR (400 MHz, CDCl3) δ 7.61−7.60 (m, 2H), 7.48 (t, J = 7.6 Hz, 2H), 7.43−7.40 (m, 1H), 7.27−7.26 (m, 2H), 7.23−7.15 (m, 5H), 7.11−7.05 (m, 3H), 7.00−6.96 (m, 2H), 6.74 (d, J = 8.4 Hz, 2H), 6.61 (d, J = 8.0 Hz, 2H), 3.17 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 141.4, 141.1, 140.7, 135.9, 135.2, 134.7, 132.3, 132.0, 131.6, 131.1, 130.3, 129.8, 128.4, 128.2, 127.5, 127.3, 127.2, 126.4, 126.3, 125.6, 125.3, 122.3, 115.8, 35.9. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C33H25ClN [M + H]+ 470.1676; found 470.1677. 3-(4-Bromophenyl)-1-methyl-2,4,7-triphenyl-1H-indol (4f). This compound was prepared according to general procedure 3 and purified by silica gel column (PE/EA 50:1−10:1): 114.2 mg, 88%, white solid, mp 279−281 °C. 1H NMR (400 MHz, CDCl3) δ 7.61−7.60 (m, 2H), 7.48 (t, J = 7.6 Hz, 2H), 7.43−7.40 (m, 1H), 7.27−7.26 (m, 2H), 7.22−6.97 (m, 10H), 6.90 (d, J = 8.0 Hz, 2H), 6.55 (d, J = 7.6 Hz, 2H), 3.17 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 141.3, 141.1, 140.6, 135.9, 135.2, 135.1, 132.6, 131.9, 131.6, 130.3, 130.2, 129.7, 128.5, 128.2, 127.5, 127.4, 126.4, 126.3, 125.6, 125.4, 122.3, 119.2, 115.8, 35.9. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C33H25BrN 514.1170; found 514.1165. 2471

DOI: 10.1021/acs.joc.7b03158 J. Org. Chem. 2018, 83, 2467−2472

The Journal of Organic Chemistry

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(ESI-TOF) m/z: [M + H]+ calcd for C32H25FNO 458.1920; found 458.1924. 3-(3,4-Dichlorophenyl)-1,9-dimethyl-2,9-diphenyl-1,9-dihydro4H-benzo[f ]indol-4-one (5d). This compound was prepared according to general procedure 4 and purified by silica gel column (PE/EA 50:1−10:1): 80.3 mg, 64%, brown solid, mp 253−255 °C. 1H NMR (400 MHz, CDCl3) δ 8.29 (dd, J = 7.6, 1.2 Hz, 1H), 7.40−7.27 (m, 12H), 7.18 (dd, J = 8.4, 2.0 Hz, 1H), 7.13−7.08 (m, 3H), 3.00 (s, 3H), 2.15 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 180.7, 149.2, 147.4, 144.0, 135.7, 135.0, 133.2, 132.4, 131.6, 131.4, 130.9, 130.8, 130.3, 129.4, 128.9, 128.7, 128.6, 128.6, 127.8, 127.5, 126.9, 126.9, 119.6, 116.6, 45.4, 33.6, 28.1. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H24Cl2NO 508.1235; found 508.1244. 3-(4-Chlorophenyl)-1,9-dimethyl-2,9-diphenyl-1,9-dihydro-4Hbenzo[f ]indol-4-one (5e). This compound was prepared according to general procedure 4 and purified by silica gel column (PE/EA 50:1− 10:1): 82.5 mg, 62%, brown solid, mp 261−263 °C. 1H NMR (400 MHz, CDCl3) δ 8.29 (dd, J = 7.6, 1.6 Hz, 1H), 7.41−7.32 (m, 6H), 7.30−7.28 (m, 4H), 7.25−7.24 (m, 2H), 7.20−7.18 (m, 2H), 7.13− 7.08 (m, 3H), 3.01 (s, 3H), 2.16 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 180.8, 149.4, 147.5, 144.0, 135.3, 133.2, 132.7, 132.3, 132.2, 131.7, 131.5, 131.2, 129.4, 128.7, 128.6, 128.4, 127.8, 127.5, 126.9, 126.9, 121.0, 116.6, 45.2, 33.6, 28.0. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H25ClNO 474.1625; found 474.1631. 3-(4-Bromophenyl)-1,9-dimethyl-2,9-diphenyl-1,9-dihydro-4Hbenzo[f ]indol-4-one (5f). This compound was prepared according to general procedure 4 and purified by silica gel column (PE/EA 50:1− 10:1): 86.5 mg, 68%, brown solid, mp 267−269 °C. 1H NMR (400 MHz, CDCl3) δ 8.29 (d, J = 8.0 Hz, 1H), 7.40−7.28 (m, 12H), 7.21− 7.19 (m, 2H), 7.12−7.08 (m, 3H), 3.01 (s, 3H), 2.16 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 180.8, 149.2, 147.4, 144.2, 135.4, 133.9, 133.2, 132.4, 131.7, 131.6, 131.3, 130.8, 129.5, 128.8, 128.7, 128.5, 127.9, 127.5, 127.0, 126.9, 120.8, 120.7, 116.6, 45.5, 33.6, 28.2. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H25BrNO 518.1120; found 518.1122. 2-(3,4-Dichorophenyl)-1,9-dimethyl-3,9-diphenyl-1,9-dihydro4H-benzo[f ]indol-4-one (5g). This compound was prepared according to general procedure 4 and purified by silica gel column (PE/EA 50:1−10:1): 98.7 mg, 76%, brown solid, mp 229−231 °C. 1H NMR (400 MHz, CDCl3) δ 8.28 (d, J = 8.0 Hz, 1H), 7.39−7.25 (m, 14H), 7.08 (d, J = 7.6 Hz, 1H), 6.95 (dd, J = 8.0, 2.0 Hz, 1H), 3.04 (s, 3H), 2.16 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 180.5, 149.1, 147.5, 144.0, 134.1, 133.2, 132.7, 132.5, 132.4, 132.4, 131.6, 131.5, 131.2, 131.1, 130.6, 129.5, 128.6, 127.8, 127.8, 127.5, 127.0, 126.9, 126.9, 123.1, 116.9, 45.4, 33.6, 28.2. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H24Cl2NO 508.1235; found 508.1237. 3-(4-Fluorophenyl)-1,4,4-trimethyl-2-phenyl-1,4-dihydro-9Hbenzo[f ]indol-9-one (6a). This compound was prepared according to general procedure 4 and purified by silica gel column (PE/EA 50:1− 10:1): 99 mg, 99%, brown solid, mp 240−242 °C. 1H NMR (400 MHz, CDCl3) δ 8.36 (d, J = 8.0 Hz, 1H), 7.56 (d, J = 3.2 Hz, 2H), 7.43−7.39 (m, 1H), 7.28−7.26 (m, 3H), 7.22−7.16 (m, 4H), 6.94 (t, J = 8.0 Hz, 2H), 4.02 (s, 3H), 1.54 (s, 6H). 13C{1H} NMR (100 MHz, CDCl3) δ 176.1, 163.4, 161.0, 151.8, 142.7, 140.8, 134.3 (two peaks), 132.5, 132.4 (two peaks), 132.1, 130.9, 130.7, 128.6, 128.4, 126.7, 126.6, 126.5, 124.6, 121.8, 115.0, 114.8, 38.2, 35.0, 31.3. HRMS (ESITOF) m/z: [M + H]+ calcd for C27H23FNO 396.1764; found 396.1771. 1,4,4-Trimethyl-2,3-diphenyl-1,4-dihydro-9H-benzo[f ]indol-9one (6b). This compound was prepared according to general procedure 4 and purified by silica gel column (PE/EA 50:1−10:1): 89.7 mg, 95%, brown solid, mp 263−265 °C. 1H NMR (400 MHz, CDCl3) δ 8.37 (d, J = 7.6 Hz, 1H), 7.56−7.55 (m, 2H), 7.43−7.39 (m, 1H), 7.24−7.18 (m, 10H), 4.03 (s, 3H), 1.55 (s, 6H). 13C{1H} NMR (100 MHz, CDCl3) δ 175.8, 151.7, 142.3, 140.5, 136.2, 132.6, 132.3, 131.8, 130.7, 130.6, 128.2, 128.1, 127.6, 127.0, 126.5, 126.3, 126.2, 124.3, 122.8, 38.0, 34.8, 31.0. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C27H24NO 378.1858; found 378.1861.

Note

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b03158. NMR spectra for 1a−l, 2a−g, 3a, 3b, 4a−i, 5a−g, 6a, 6b, and X-ray crystallography data for 2a and 5f (PDF) X-ray crystallography data for 2a (CIF) X-ray crystallography data for 5f (CIF)

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Jian-Ping Qu: 0000-0002-5002-5594 Yan-Biao Kang: 0000-0002-7537-4627 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank the National Natural Science Foundation of China (NSFC 21672196, 21602001, 21404096, U1463202) for financial support.

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REFERENCES

(1) (a) O’Hagan, D. Nat. Prod. Rep. 2000, 17, 435. (b) Fattorusso, E.; Taglialatela-Scafati, O. Modern Alkaloids: Structure, Isolation, Synthesis, Biology; Wiley-VCH: Weinheim, Germany, 2007. (2) (a) Royer, J.; Bonin, M.; Micouin, L. Chem. Rev. 2004, 104, 2311. (b) Pandey, G.; Banerjee, P.; Gadre, S. R. Chem. Rev. 2006, 106, 4484. (3) (a) Ma, S.; Jiao, N. Angew. Chem., Int. Ed. 2002, 41, 4737. (b) Shi, M.; Liu, L.-P.; Tang, J. Org. Lett. 2006, 8, 4043. (c) Bertrand, M. B.; Neukom, J. D.; Wolfe, J. P. J. Org. Chem. 2008, 73, 8851. (d) Chen, X.H.; Wei, Q.; Luo, S.-W.; Xiao, H.; Gong, L.-Z. J. Am. Chem. Soc. 2009, 131, 13819. (e) Yang, W.-L.; Tang, F.-F.; He, F.-S.; Li, C.-Y.; Yu, X.; Deng, W.-P. Org. Lett. 2015, 17, 4822. (f) Zhang, L.; Xu, X.; Shao, Q.R.; Pan, L.; Liu, Q. Org. Biomol. Chem. 2013, 11, 7393. (4) (a) Yao, C.-Z.; Xiao, Z.-F.; Liu, J.; Ning, X.-S.; Kang, Y.-B. Org. Lett. 2014, 16, 2498. (b) Yao, C.-Z.; Xiao, Z.-F.; Ning, X.-S.; Liu, J.; Zhang, X.-W.; Kang, Y.-B. Org. Lett. 2014, 16, 5824. (c) Xiao, Z.-F.; Yao, C.-Z.; Kang, Y.-B. Org. Lett. 2014, 16, 6512. (d) Xiao, Z.-F.; Ding, T.-H.; Mao, S.-W.; Ning, X.-S.; Kang, Y.-B. Adv. Synth. Catal. 2016, 358, 1859. (e) Xiao, Z.-F.; Ding, T.-H.; Mao, S.-W.; Shah, Z.; Ning, X.S.; Kang, Y.-B. Org. Lett. 2016, 18, 5672. (5) McKeage, K. Drugs 2015, 75, 75.

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DOI: 10.1021/acs.joc.7b03158 J. Org. Chem. 2018, 83, 2467−2472