Synthesis of Highly Functionalized Indoles and Indolones via

1 hour ago - Highly functionalized indoles and indolones were prepared via selectivity-switchable mono- or diolefinations. The Julia olefination of th...
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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 J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b03158 • Publication Date (Web): 29 Jan 2018 Downloaded from http://pubs.acs.org on January 30, 2018

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The Journal of Organic Chemistry

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 Supporting Information Placeholder

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.

Substituted 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, consequentially, the research on the convenient construction of such heterocycles has always attracted chemists.2 Despite numerous methods have been established in this area,3 the construction of multiple-substituted pyrroles and indoles in 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 the further study, it was found that the selectivity of the olefination of 2,3-dicarbonyl pyrroles could be controlled. The Wittig olefination generates 1,5-dienes which 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 2,3-dicarbonyl 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 is noteworthy to mention that when the R3 substituent is an aryl group the olefination occurs on the ketone on 3-position of pyrrole, whereas when the R3 substituent is a methyl group the olefination occurs on the ketone on 2-position of pyrrole. The reason is unclear. The structure of mono-olefination product 2a was confirmed by the 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 oC 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 U.S. in 2015, is an orally active inhibitor of anaplastic lymphoma kinase for the treatment of ALK-positive 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).

Figure 1. Representative 4-Indolone containing compounds.

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-indolone or 7indolone, 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). Scheme 1. Selective-Switchable Olefinationa

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The Journal of Organic Chemistry O

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

R2 R1

O

R2

R3 Ph or N Me

R3

Julia

R4

R5

Ph

R1

N Me

2

O

1 A R

3

R3 N R2 1

Ph

R4

Wittig R1

N R2

B O

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olefin stage due to the no acceleration of chelating groups. The mechanistic insight is still under investigation. Scheme 2. Synthesis of Indolonesa

Ph 4

Julia

TfOH, 80 C

2 or 3

Ph

O R

Ph

N Me

F

O N Me

Ph Ph

Ph N Me

5a, 80 %

Ph

5b, 96 %

(Br)

Cl O

N Me

O

Ph

Ph

Ph N Me

4g, 84 %

N Me

Ph

5d, 64 % O Ph

Cl

Ph Ph

N Me

N Me

Ph

Ph

N Me

O

3a, R = 4-F-C6H4, 82% 3b, R = C6H5, 64%

Ph

N Me

Ph

Ph N Me

O 6a, 99 %

N Me

O

6b, 95 %

a

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

Ph Ph

N Me 5g, 76 %

Me

Ph Ph

Cl

MeO R

O

Cl

4h, quant

2g, 64% (68% brsm)

(CCDC1585936) 5f, 68 %

F

Ph

Cl

Ph

5e, 62 %

Ph

F

N Me Ph 5c, 60 %

Ph

Cl

Me Ph

O

Ph

Cl

Ph

O 6

O

Ph

4a, R = C6H5, 72% 4b, R = 4-Me-C6H4, 84% 4c, R = 4-F-C6H4, 80% 4d, R = 3,4-Cl2-C6H3, 52%b 4e, R = 4-Cl-C6H4, 68% 4f, R = 4-Br-C6H4, 88%

N Me

2b, R = 4-Me-C6H4, 76% 2c, R = 4-F-C6H4, 99% 2d, R = 3,4-Cl2-C6H3, 46% (72% brsm) 2e, R = 4-Cl-C6H4, 99% 2f, R = 4-Br-C6H4, 68% (94% brsm)

R1 N Me

Ph

Ph

Ph Ph

or

5

Ph

(CCDC1585935)

R2

R1 N Me

R

2a, 64% (94% brsm)

O

R2

Wittig

Ph

4i, quant

a

Condition A for Julia olefination: 1 (0.5 mmol), LiHMDS (4 mmol), 5-(methylsulfonyl)-1-phenyl-1H-tetrazole (2 mmol), THF (5 mL). Condition 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. b Dioxane instead of THF, 100 °C. 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 oC in toluene, followed by the dehydrogenation with DDQ to afford 1. Other catalyst including [RuCl2(p-cymene)]2 and RuCl3-4,4'-(Me)2biPy complex afford moderate yields.4e A proposed mechanism for explaining the mono- and diolefination is demonstrated (Scheme 3). The Wittig olefination passes through a [2+2] cycloaddition whereas the Juliaolefination takes place via a neighboring carbonyl 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 LiHMDS as a base. The [2+2] cycloaddition does not need a participation of neighboring carbonyl which enables the Wittig olefination of both carbonyl groups. The Julia-olefination stops at the mono-

Scheme 3. Proposed Mechanism

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 olefination-

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The Journal of Organic Chemistry electrocyclization of the cyclization product afforded substituted indoles. Julia olefination of the cyclization product could occur selectively on the carbonyl group. The following cyclization prompted by Brønsted acid afforded multiple substituted indolones.

EXPERIMENTAL SECTION General Information. Solvents were pre-dried over activated MS 4Å 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'-dimethyl2,2'-bipyridine (18.4 mg, 0.1 mmol) in 1 mL dry MeOH were stirred 75 oC 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 deionized H2O were added sequentially and stirred at 110 oC for 5 min, cooled to rt and 2,3-dihydroisoxazoles (0.5 mmol), alkenes (0.5 mmol) and another 1 mL dry toluene were added, the reaction was stirred at 110 oC and monitored by TLC. The reaction mixture was cooled to rt and DDQ (2.0 equiv) was added and stirred at 110 oC and monitored by TLC. The reaction mixture was cooled to rt and 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 the 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 into a suspension of NaH (2.0 mmol) in dry THF under argon atmosphere at 0 oC. 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 the 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 ℃ until the 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-2,3diyl)bis(phenylmethanone) (1a). Prepared according to General procedure 1, purified by silica gel column (PE/EA 50:1-10:1), 189.9 mg, 86%, yellow solid, mp 157-159 ℃. 1H NMR (400 MHz, CDCl3) δ 7.43-7.26 (m, 11H), 7.15-7.05 (m, 9H), 3.81 (s, 3H). 13C{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-2,3diyl)bis(phenylmethanone) (1b). Prepared according to General procedure 1, purified by silica gel column (PE/EA 50:1-10:1), 88.8 mg, 39%, yellow solid, mp 145-146 oC. 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, 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-2,3diyl)bis(phenylmethanone) (1c). Prepared according to General procedure 1, purified by silica gel column (PE/EA 50:1-10:1), 160.8 mg, 69%, yellow solid, mp 154-156 ℃. 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-2,3diyl)bis(phenylmethanone) (1d). Prepared according to General procedure 1, purified by silica gel column (PE/EA 50:1-10:1), 168.4 mg, 66%, yellow solid, mp 215-217 oC. 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-2,3diyl)bis(phenylmethanone) (1e). Prepared according to General procedure 1, purified by silica gel column (PE/EA 50:1-10:1), 180.9 mg, 76%, yellow solid. mp 124-126 oC. 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-2,3diyl)bis(phenylmethanone) (1f). Prepared according to General procedure 1, purified by silica gel column (PE/EA 50:1-10:1), 171.7 mg, 66%, yellow solid, mp 143-145 oC. 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-2,3diyl)bis(phenylmethanone) (1g). Prepared according to General procedure 1, purified by silica gel column (PE/EA 50:1-10:1), 127.6 mg, 50%, yellow solid, mp 215-217 oC. 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.

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The Journal of Organic Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

1-(2-benzoyl-4-(4-fluorophenyl)-1-methyl-5-phenyl-1H-pyrrol3-yl)ethan-1-one (1h). Prepared according to General procedure 1, purified by silica gel column (PE/EA 50:1-10:1), 65.6 mg, 33%, yellow solid, mp 193-195 oC. 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). 13C{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 (ESI-TOF) 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-1one (1i). Prepared according to General procedure 1, purified by silica gel column (PE/EA 50:1-10:1), 106.2 mg, 56%, yellow solid, mp 189-192 oC. 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, 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-2,3diyl)bis(phenylmethanone) (1j). Prepared according to General procedure 1, purified by silica gel column (PE/EA 50:1-10:1), 97.9 mg, 43%, yellow solid, mp 192-194 oC. 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-fluoroohenyl)-1-methyl-5-phenyl-1H-pyrrole-2,3diyl)bis(phenylmethanone) (1k). Prepared according to General procedure 1, purified by silica gel column (PE/EA 50:1-10:1), 181.5 mg, 79%, yellow solid, mp 174-176 oC. 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-2,3diyl)bis(phenylmethanone) (1l). Prepared according to General procedure 1, purified by silica gel column (PE/EA 50:1-10:1), 146.2mg, 62%, yellow solid, mp 146-149 oC. 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-3yl)(phenyl)methanone (2a). Prepared according to General procedure 2, purified by silica gel column (PE/EA 50:1-10:1), 141 mg, 64% (the starting material has been recovered in 30%, 66 mg), yellow foam, mp 147-150 oC. 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). 13C{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-3yl)(phenyl)methanone (2b). Prepared according to General procedure 2, purified by silica gel column (PE/EA 50:1-10:1), 277.5 mg, 76%, yellow foam, mp 152-154 oC. 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)-1Hpyrrol-3-yl)(phenyl)methanone (2c). Prepared according to General procedure 2, purified by silica gel column (PE/EA 50:110:1), 226.5 mg, 99%, yellow foam, mp 175-177 oC. 1H 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, 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)1H-pyrrol-3-yl)(phenyl)methanone (2d). Prepared according to General procedure 2, purified by silica gel column (PE/EA 50:110:1), 508.44 mg, 46% (the starting material has been recovered in 36%, 93.8 mg), yellow foam, mp 147-149 oC. 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)-1Hpyrrol-3-yl)(phenyl)methanone (2e). Prepared according to General procedure 2, purified by silica gel column (PE/EA 50:110:1), 234.6 mg, 99%, yellow foam, mp 126-128 oC. 1H 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)-1Hpyrrol-3-yl)(phenyl)methanone (2f). Prepared according to General procedure 2, purified by silica gel column (PE/EA 50:110:1), 170.2 mg, 68%, the starting materials have recovered 26% (69.2 mg), yellow foam, mp 132-134 oC. 1H NMR (400 MHz, CDCl3) δ 7.68 (dd, J = 8.0 , 1.2 Hz, 2H), 7.35-7.28 (m, 9H), 7.257.23 (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)1H-pyrrol-3-yl)(phenyl)methanone (2g). Prepared according to

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The Journal of Organic Chemistry General procedure 2, purified by silica gel column (PE/EA 50:110:1), 163.3 mg, 64% (the starting materials have recovered 4%,10.2 mg), yellow foam, mp 205-207 oC. 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). Prepared according to General procedure 2, purified by silica gel column (PE/EA 50:110:1), 164.1 mg, 82%, yellow foam, mp 167-169 oC. 1H 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-2yl)(phenyl)methanone (3b). Prepared according to General procedure 2, purified by silica gel column (PE/EA 50:1-10:1), 121.8mg, 64%, yellow foam, mp 177-179 oC. 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, 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). Prepared according to General procedure 3, purified by silica gel column (PE/EA 50:1-10:1), 78.6 mg, 72%, white solid, mp 182-184 oC. 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), 6.886.85 (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). Prepared according to General procedure 3, purified by silica gel column (PE/EA 50:1-10:1), 92.4 mg, 84%, white solid, mp 219-222 oC. 1 H 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). Prepared according to General procedure 3, purified by silica gel column (PE/EA 50:1-10:1), 90.6 mg, 80%, white solid, mp 239241 oC. 1H NMR (400 MHz, CDCl3) δ 7.62-7.60 (m, 2H), 7.48 (t, J = 7.6Hz, 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). Prepared according to General procedure 3, purified by silica gel column (PE/EA 50:1-10:1), 77.4 mg, 52%, white solid, mp 197-200 oC. 1 H 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). 13 C{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). Prepared according to General procedure 3, purified by silica gel column (PE/EA 50:1-10:1), 79.7 mg, 68%, white solid, mp 262264 oC. 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). Prepared according to General procedure 3, purified by silica gel column (PE/EA 50:1-10:1), 114.2 mg, 88%, white solid, mp 279281 oC. 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. 1-methyl-2,4,7-triphenyl-3-(o-tolyl)-1H-indol (4g). Prepared according to General procedure 3, purified by silica gel column (PE/EA 50:1-10:1), 94.4 mg, 84%, white solid, mp 179-181 oC. 1 H 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 (ESITOF) m/z: [M+H]+ Calcd for C34H28N 450.2222; Found 450.2213. 3-(3-fluorophenyl)-1-methyl-2,4,7-triphenyl-1H-indol (4h). Prepared according to General procedure 3, purified by silica gel column (PE/EA 50:1-10:1), 121 mg, quant, white solid, mp 199202 oC. 1H NMR (400 MHz, CDCl3) δ 7.62-7.60 (m, 2H), 7.497.45 (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.

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The Journal of Organic Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

3-(4-methoxyphenyl)-1-methyl-2,4,7-triphenyl-1H-indol (4i). Prepared according to General procedure 3, purified by silica gel column (PE/EA 50:1-10:1), 121.4 mg, quant, white solid, mp 135138 oC. 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). Prepared according to General procedure 4, purified by silica gel column (PE/EA 50:1-10:1), 86.9 mg, 80%, brown solid, mp 234-236 oC. 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-4Hbenzo[f]indol-4-one (5b). Prepared according to General procedure 4, purified by silica gel column (PE/EA 50:1-10:1), 109.4 mg, 96%, brown solid, mp 241-244 oC. 1H NMR (400 MHz, CDCl3) δ 8.30 (d, J = 7.6 Hz, 1H), 7.39-7.30 (m, 8H), 7.287.18 (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). Prepared according to General procedure 4, purified by silica gel column (PE/EA 50:1-10:1), 68.6 mg, 60%, brown solid, mp 237-239 oC. 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 (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). Prepared according to General procedure 4, purified by silica gel column (PE/EA 50:1-10:1), 80.3 mg, 64%, brown solid, mp 253-255 oC. 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). Prepared according to General procedure 4, purified by silica gel column (PE/EA 50:1-10:1), 82.5 mg, 62%, brown solid, mp 261-263 oC. 1H NMR (400 MHz, CDCl3) δ 8.29 (dd, J = 7.6, 1.6 Hz, 1H), 7.41-7.32 (m, 6H), 7.307.28 (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). Prepared according to General procedure 4, purified by silica gel column (PE/EA 50:1-10:1), 86.5 mg, 68%, brown solid, mp 267-269 oC. 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). Prepared according to General procedure 4, purified by silica gel column (PE/EA 50:1-10:1), 98.7 mg, 76%, brown solid, mp 229-231 oC. 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). Prepared according to General procedure 4, purified by silica gel column (PE/EA 50:1-10:1), 99 mg, 99%, brown solid, mp 240-242 oC. 1H NMR (400 MHz, CDCl3) δ 8.36 (d, J = 8.0 Hz, 1H), 7.56 (d, J = 3.2 Hz, 2H), 7.437.39 (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 (ESI-TOF) 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). Prepared according to General procedure 4, purified by silica gel column (PE/EA 50:1-10:1), 89.7 mg, 95%, brown solid, mp 263-265 oC. 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.

ASSOCIATED CONTENT Supporting Information NMR spectra for 1a-l, 2a-g, 3a-b, 4a-i, 5a-g, 6a-b, and X-ray crystallography data for 2a and 5f. This material is available free of charge via the Internet at http://pubs.acs.org. SI (PDF)

AUTHOR INFORMATION [email protected] [email protected]

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

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The Journal of Organic Chemistry Notes The authors declare no competing financial interest.

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

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