Intramolecular Cyclization: Access to

Nov 30, 2017 - Rh(III)-Catalyzed C–H Activation/Intramolecular Cyclization: Access to N-Acyl-2,3-dihydro-1H-carbazol-4(9H)-ones from Cyclic 2-Diazo-...
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Article Cite This: ACS Omega 2017, 2, 8507−8516

Rh(III)-Catalyzed C−H Activation/Intramolecular Cyclization: Access to N‑Acyl-2,3-dihydro‑1H‑carbazol-4(9H)‑ones from Cyclic 2‑Diazo1,3-diketones and N‑Arylamides Youpeng Zuo, Xinwei He, Yi Ning, Yuhao Wu, and Yongjia Shang* Key Laboratory of Functional Molecular Solids, Ministry of Education, Anhui Laboratory of Molecule-Based Materials (State Key Laboratory Cultivation Base), College of Chemistry and Materials Science, Anhui Normal University, Wuhu 241000, P.R. China S Supporting Information *

ABSTRACT: A Rh(III)-catalyzed C−H activation/cyclization cascade reaction is described. The reaction involves cyclic 2diazo-1,3-diketones and N-arylamides, and it proceeds via an intermolecular C−C bond formation and subsequent intramolecular C−N bond formation. A variety of N-acyl-2,3dihydro-1H-carbazol-4(9H)-ones were obtained under mild conditions in good to excellent yields (65−90%). Key features of this strategy include high-efficiency, operational simplicity, scalability, and broad functional-group tolerance. In addition, H2O and N2 are the only byproducts. Carbazole derivatives with free NH groups can be easily obtained through N-deprotection reactions.

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INTRODUCTION Dihydrocarbazole scaffolds are the most important building blocks in total synthesis of many natural products and biologically active compounds1,2 and fluorescent probes.3 In addition, they are widely used in organic luminescent materials because of their conjugated coplanar structures.4 Because of their excellent physical and chemical properties, a variety of efficient and accurate methods for the synthesis of dihydrocarbazole and their derivates have been reported.5 Traditionally, dihydrocarbazole scaffolds are constructed via the well-known Fischer-indole synthesis,6 reductive cylization,7 intramolecular arylation,8 oxidative cylization9 mainly using indoles,10 anilines,11 or nitrobenzenes12 as starting materials. The development of more efficient and general methods for the synthesis of dihydrocarbazole compounds remains an attractive challenge. Diazo compounds are important and versatile building blocks in organic synthesis and have been widely studied.13 The transition-metal-catalyzed transformations of diazo compounds to carbenoids and their diversified reactivities have been welldeveloped.14 In addition, Cp*Rh(III)-catalyzed C−H activation/cyclization has also emerged as a versatile and stepeconomic approach for building diverse carbocycles and heterocycles via the formation of carbon−carbon and carbon−heteroatom bonds.15 Recently, cyclic 2-diazo-1,3diketones, having higher stability and dipole moments, are important building blocks in synthetic organic chemistry. Several new reactions of cyclic 2-diazo-1,3-diketones, including Wolff rearrangement,16 1,3-dipolar cycloadditions,17 and other reactions,18 have been developed. Previously, we described Rhcatalyzed reactions of cyclic 2-diazo-1,3-diketones with aryl isothiocyanates, benzoic acids, and isocyanides for the synthesis of 2-arylimino-6,7-dihydrobenzo[d][1,3]oxathiol-4(5H)-ones, isocoumarins, and 2-hydroxy-6-oxocyclohex-1-enecarboxamides.19 In a continuation of our exploration of transformations © 2017 American Chemical Society

of diazo compounds and the synthesis of heterocycles, we herein report a convenient method for the synthesis of carbazole derivatives via a Rh(III)-catalyzed C−H bond functionalization/intramolecular cyclization with cyclic 2diazo-1,3-diketones and arylamides (Scheme 1). Scheme 1. Rh(III)-Catalyst C−H Functionalization for the Synthesis of Dihydrocarbazole Derivatives

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RESULTS AND DISCUSSION The reaction was initially tested with 2-diazo-5,5-dimethylcyclohexane-1,3-dione (1e) and acetanilide (2a) as model substrates to optimize the reaction conditions (Table 1). The desired product, 3ea, was generated in 81% yield when the reaction was carried out with [Cp*RhCl2]2 (1.0 mol %) and AgNTf2 (10 mol %) in 1,2-dichloroethane (DCE) for 12 h (Table 1, entry 4). The structure of 3ea was unequivocally determined by X-ray diffraction measurements (see the Supporting Information). The yield of 3ea decreased sharply to 49% when the loading of AgNTf2 was decreased to 5 mol % (Table 1, entry 11). The results were not improved by increasing the AgNTf2 loading to 20 mol % (Table 1, entry 12). A screening of Rh-catalysts revealed that Rh(PPh3)3Cl and Rh2(OAc)4 were ineffective in the reaction, and only trace Received: October 25, 2017 Accepted: November 17, 2017 Published: November 30, 2017 8507

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ACS Omega Table 1. Optimization of Reaction Conditionsa

entry

catalyst

additive

solvent

temp (°C)

yield (%)b

1 2 3 4 5 6 7 8 9 10 11c 12d 13e 14f 15 16 17 18

Rh(PPh3)3Cl Rh2(OAc)4 [Cp*Co(CO)I2] [Cp*RhCl2]2

AgNTf2 AgNTf2 AgNTf2 AgNTf2 AgNTf2 AgNTf2 AgNTf2 AgNTf2 AgNTf2 AgNTf2 AgNTf2 AgNTf2 AgNTf2 AgNTf2 AgNTf2 AgNTf2 AgNTf2 AgNTf2

DCE DCE DCE DCE DCE MeOH EtOH toluene DCM TFEA DCE DCE DCE DCE DCE DCE DCE DCE

reflux reflux reflux reflux reflux reflux reflux 100 reflux reflux reflux reflux reflux reflux rt 40 60 80

trace trace trace 81 trace 31 35 56 51 28 49 75 46 78 trace 18 32 65

[Cp*RhCl2]2 [Cp*RhCl2]2 [Cp*RhCl2]2 [Cp*RhCl2]2 [Cp*RhCl2]2 [Cp*RhCl2]2 [Cp*RhCl2]2 [Cp*RhCl2]2 [Cp*RhCl2]2 [Cp*RhCl2]2 [Cp*RhCl2]2 [Cp*RhCl2]2 [Cp*RhCl2]2

and 1e), when N-arylacetamides 2 bearing withdrawingelectronic groups (e.g., −Cl, −Br, and −CF3) were used, the reaction was almost completely suppressed illustrating that the electronic effect of the aromatic ring bearing withdrawingelectronic group may reduce the activity of the C−H bond of the aromatic ring. Furthermore, we carried out a gram-scale reaction of 2-diazo5,5-dimethylcyclohexane-1,3-dione (1e, 10 mmol) and acetanilide (2a, 10 mmol) under the standard conditions, and the desired product, 3ea, was isolated in 78% (1.99 g) yield (Scheme 2). This demonstrated the applicability of this method as a useful tool in practical synthetic contexts. Subsequently, the scope of N-acylanilines was investigated, and the results are summarized in Table 3. Various Nacylanilines bearing alkyl (2m), benzyl (2n) and cyclohexyl (2o) groups could react with 2-diazo-5,5-dimethylcyclohexane1,3-dione (1e) to give the desired products 3em, 3en, and 3eo in 86, 78, and 81% yields, respectively (Table 3, entries 4−6). In addition, we have also explored the generality of our reaction using other cyclic 2-diazo-1,3-diketones as substrates. The reactions of 1a with 2m and 1c with 2m and 2n under the above reaction conditions afforded good yields (86, 76, and 73%, respectively) of the corresponding products (3am, 3cm, and 3cn, respectively) (Table 3, entries 1−3). These examples prove the generality of this method. Because of the prevalence of carbazoles with a free NH group in the cores of a large number of natural products and privileged heterocyclic compounds possessing significant biological activities, we tested N-deprotection reactions on a few representative compounds (3ea and 3en) as shown in Scheme 3. The transformations of 3ea and 3en can easily be accomplished using NaOH in EtOH at room temperature for 10 min, and the corresponding free NH product, 4ea, was obtained in excellent yield (95%). Furthermore, the mechanism of this reaction system was examined by the deuterium experiments. The reaction of 1e with the same amounts of both 2a and 2a-d5 was explored under the standard conditions for 2 h. A significant kinetic isotope effect (KIE) value of 2.5 was measured based on 1H NMR analysis (Scheme 4 eq 1). Then, separate reactions of 1e with either 2a or 2a-d5 were performed in parallel, and a similar KIE value of 2.0 was obtained (Scheme 4 eq 2). These results suggested that C−H cleavage may be involved in the ratedetermining step.20 Based on the experimental results and literature reports,19a,21 a plausible mechanism was proposed and is shown in Scheme 5. First, treatment of [Cp*RhCl2]2 with AgNTf2 generated the active catalytic species A, which was followed by C−H bond activation of arylamide 2 with the Rh(III) to generate rhodacycle B. Coordination and subsequent migratory insertion afforded intermediate D, which then regenerated catalytic species A and released intermediate E. Tautomerization of intermediate E generates enol intermediate F in situ, which then cyclizes via the elimination of water to generate final product 3.

a

Reaction conditions: 2-diazo-5,5-dimethylcyclohexane-1,3-dione 1e (0.5 mmol), acetanilide 2a (0.5 mmol), solvent (3 mL), and catalyst (1.0 mol %) for 12 h. bIsolated yields. c5 mol % of additive was used. d 20 mol % of additive was used. e0.5 mol % of catalyst was used. f2 mol % of catalyst was used.

amounts of the product were detected in each case (Table 1, entries 1, 4). Other transition-metal catalysts were also investigated, and all led to inferior results (Table 1, entry 3, and Table S1 in the Supporting Information). [Cp*RhCl2]2 was found to be the best catalyst (Table 1, entries 13 and 14). Then, the effect of solvents was tested. The yield of the reaction is relatively low in MeOH, EtOH, toluene, DCM (dichloromethane), TFEA (2,2,2-trifluoroethanol) compared to that of DCE (Table 1, entries 6−10). Lower temperatures led to lower yields (Table 1, entries 15−18). Thus, the conditions used in entry 3 were selected as the optimized conditions for the reaction. With the optimized conditions in hand, we set out to explore the generality of this reaction (Table 2). Various cyclic 2-diazo1,3-diketones and N-arylacetamides were tested, and the results are summarized in Table 2. A series of carbazole derivatives were obtained in good to excellent yields (65−90%). For Narylacetamides 2, both electron-donating and electron-withdrawing groups on the N-aryl ring of the acetamides were welltolerated, and the corresponding carbazoles were generated in appreciable yields. Notably, functional groups such as chloro, bromo, fluoro, methyl, methoxyl, tert-butyl, trifluoromethyl, and acetyl on the N-aryl ring of the acetamides were well-tolerated, and the steric hindrance and electronic effects did not noticeably influence the transformation. The scope of the substituents on the cyclic 2-diazo-1,3-diketones was then examined. Generally, the reaction using substrates bearing alkyl (e.g., CH3) and aryl (e.g., phenyl or 4-ClC6H4) groups for R1 proceeded smoothly, and the desired carbazole derivatives were synthesized in good to excellent yields (65−90%). As for cyclic 2-diazo-1,3-diketones bearing H and alkyl groups (1c, 1d,

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CONCLUSION In summary, we have developed an efficient route to dihydrocarbazole derivatives from easily available cyclic diazo1,3-diketones and N-arylamides. The process involves C−H activation/intramolecular cyclization and proceeded smoothly with broad functional group tolerance and high atom efficiency. 8508

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ACS Omega Table 2. Rh(III)-Catalyzed Reactions of Various Cyclic 2-Diazo-1,3-diketones and N-Arylacetamidesa,b

a

Reaction conditions: cyclic 2-dizao-1,3-diketone 1 (0.5 mmol), N-arylacetamides 2 (0.5 mmol), [Cp*RhCl2]2 (1 mol %), and AgNTf2 (10 mol %) in DCE (3 mL) were stirred at reflux for 12 h. bIsolated yield.

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Scheme 2. Gram-Scale Synthesis of This Method

EXPERIMENTAL SECTION

General Remarks. Unless otherwise specified, all reagents and starting materials were purchased from commercial sources and used as received, and the solvents were purified and dried using standard procedures. The chromatography solvents were of technical grade and distilled prior to use. Flash chromatography was performed using 200−300 mesh silica gel with the indicated solvent system according to standard techniques. The 1H and 13C NMR spectra were recorded using 300 MHz spectrometers unless otherwise specified. The

Dihydrocarbazole with free NH groups could be easily obtained under mild conditions. 8509

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ACS Omega

MHz, CDCl3): δ 8.36 (d, J = 8.7 Hz, 1H), 7.85 (d, J = 8.7 Hz, 1H), 7.38−7.30 (m, 7H), 3.67−3.50 (m, 2H), 3.37−3.28 (m, 1H), 2.95−2.84 (m, 2H), 2.77 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 194.4, 170.3, 150.7, 142.7, 135.7, 127.2, 126.9, 126.0, 125.2, 124.7, 122.0, 117.5, 114.3, 44.6, 42.0, 34.3, 27.5; IR (KBr) ν: 3412, 1714, 1692, 1603, 1548, 1484, 1457, 1400, 1361, 1299, 1274, 1169, 1142, 1069, 1017, 959, 907, 766, 749, 695 cm−1; HRMS (APCI): calcd for [C20H17NO2 + H]+, 304.1332; found, 304.1334. 9-Acetyl-7-methyl-2-phenyl-2,3-dihydro-1H-carbazol4(9H)-one (3ab). Petroleum ether/ethyl acetate 8:1; yield 84% (133 mg, 0.42 mmol); white solid; mp 168−170 °C; 1H NMR (300 MHz, CDCl3): δ 8.22 (d, J = 7.8 Hz, 1H), 7.69 (s, 1H), 7.40−7.29 (m, 5H), 7.21 (d, J = 7.8 Hz, 1H), 3.65−3.52 (m, 2H), 3.35−3.29 (m, 1H), 2.96−2.83 (m, 2H), 2.77 (s, 3H), 2.50 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 194.4, 170.4, 150.1, 142.7, 136.2, 135.3, 128.8, 127.2, 126.9, 126.1, 123.6, 121.6, 114.7, 44.6, 42.1, 34.3, 27.5, 22.2; IR (KBr) ν: 3458, 1721, 1648, 1637, 1600, 1557, 1470, 1395, 1356, 1341, 1261, 1208, 1131, 1062, 1028, 793, 761, 702 cm−1; HRMS (APCI): calcd for [C21H19NO2 + H]+, 318.1489; found, 318.1488. 9-Acetyl-6-methyl-2-phenyl-2,3-dihydro-1H-carbazol4(9H)-one (3ac). Petroleum ether/ethyl acetate 8:1; yield 84% (133 mg, 0.42 mmol); white solid; mp 193−195 °C; 1H NMR (300 MHz, CDCl3): δ 8.16 (s, 1H), 7.70 (d, J = 8.7 Hz, 1H), 7.40−7.29 (m, 5H), 7.17 (d, J = 8.4 Hz, 1H), 3.67−3.50 (m, 2H), 3.36−3.26 (m, 1H), 2.94−2.82 (m, 2H), 2.75 (s, 3H), 2.47 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 194.6, 170.2, 150.9, 142.8, 134.6, 133.9, 128.8, 127.2, 126.9, 126.4, 126.2, 122.0, 117.3, 114.0, 44.6, 41.9, 34.3, 27.4, 21.2; IR (KBr) ν: 3426, 1721, 1653, 1637, 1550, 1482, 1468, 1395, 1359, 1261, 1211, 1192, 1124, 1062, 889, 796, 759 cm−1; HRMS (APCI): calcd for [C21H19NO2 + H]+, 318.1489; found, 318.1486. 9-Acetyl-6-(tert-butyl)-2-phenyl-2,3-dihydro-1H-carbazol4(9H)-one (3ad). Petroleum ether/ethyl acetate 8:1; yield 87% (156 mg, 0.43 mmol); white solid; mp 192−194 °C; 1H NMR (300 MHz, CDCl3): δ 8.40 (s, 1H), 7.75 (d, J = 8.7 Hz, 1H), 7.44−7.29 (m, 6H), 3.67−3.50 (m, 2H), 3.37−3.28 (m, 1H), 2.95−2.83 (m, 2H), 2.75 (s, 3H), 1.41 (s, 9H); 13C NMR (75 MHz, CDCl3): δ 194.6, 170.2, 151.0, 148.1, 142.8, 133.7, 128.8, 127.2, 126.9, 126.1, 122.9, 118.4, 117.6, 113.8, 44.7, 41.9, 34.8, 34.3, 31.6, 27.4; IR (KBr) ν: 3462, 1719, 1669, 1605, 1555, 1480, 1459, 1395, 1366, 1299, 1272, 1181, 1078, 1010, 825, 764, 691 cm−1; HRMS (APCI): calcd for [C24H25NO2 + H]+, 360.1958; found, 360.1960. 9-Acetyl-8-bromo-2-phenyl-2,3-dihydro-1H-carbazol4(9H)-one (3ae). Petroleum ether/ethyl acetate 8:1; yield 80% (152 mg, 0.40 mmol); white solid; mp 128−130 °C; 1H NMR (300 MHz, CDCl3): δ 8.30 (d, J = 7.8 Hz, 1H), 7.51 (d, J = 7.8 Hz, 1H), 7.45−7.22 (m, 6H), 3.64−3.58 (m, 1H), 3.36−3.12 (m, 2H), 2.90−2.86 (m, 2H), 2.70 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 193.7, 172.8, 150.9, 142.7, 134.8, 129.5, 129.4, 129.3, 128.5, 128.3, 127.7, 127.2, 126.1, 115.6, 106.3, 45.3, 41.9,

Table 3. Rh(III)-Catalyzed Reactions of Various Cyclic 2Diazo-1,3-diketones and N-Acylanilinesa,b

a

Reaction conditions: cyclic 2-dizao-1,3-diketone 1 (0.5 mmol), arylamide 2 (0.5 mmol), [Cp*RhCl2]2 (1 mol %), and AgNTf2 (10 mol %) in DCE (3 mL) were stirred at reflux for 12 h. bIsolated yield.

chemical shifts (δ) in parts per million are reported relative to the residual signals of chloroform (7.26 ppm for 1H and 77.16 ppm for 13C), and all 13C NMR spectra that were recorded with broadband proton decoupling are denoted 13C{1H} NMR. The multiplicities are described as s (singlet), d (doublet), t (triplet), q (quartet), or m (multiplet), and the coupling constants (J) are reported in hertz. The HRMS analyses with a quadrupole time-of-flight mass spectrometer yielded ion mass/ charge (m/z) ratios in atomic mass units. The IR spectra were measured as dry pellets (KBr), and the peaks are reported in terms of the wavenumber (cm−1). General Procedure for the Synthesis of the Dihydrocarbazole Derivatives 3. A mixture of cyclic 2-diazo-1,3diketone 1 (0.5 mmol), N-arylamide 2 (0.5 mmol), [Cp*RhCl2]2 (0.005 mmol), and AgNTf2 (0.05 mmol) in DCE (3 mL) was heated to reflux in an oil bath for 12 h. After the reaction was complete (as determined by TLC), the reaction mixture was cooled to room temperature, extracted with CH2Cl2 (3 × 10 mL), and washed with brine. The organic layers were combined, dried over Na2SO4, and filtered, and then the solvent was evaporated under vacuum. The residue was purified using flash column chromatography with silica gel (200−300 mesh) using ethyl acetate and petroleum ether (1:8−1:10, v/v) as the elution solvent to give the desired product 3. 9-Acetyl-2-phenyl-2,3-dihydro-1H-carbazol-4(9H)-one (3aa). Petroleum ether/ethyl acetate 8:1; yield 86% (130 mg, 0.43 mmol); white solid; mp 149−151 °C; 1H NMR (300 Scheme 3. N-Deprotection Reactions

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ACS Omega Scheme 4. The Deuterium Experiments

Scheme 5. Proposed Mechanism for the Rh(III)-Catalyzed C−H Activation/Cyclization of Cyclic 2-Diazo-1,3-diketones and NArylamides

31.7, 30.6; IR (KBr) ν: 3444, 1730, 1662, 1557, 1546, 1466, 1434, 1391, 1356, 1263, 1163, 1119, 786, 764, 697 cm−1; HRMS (APCI): calcd for [C20H16BrNO2 + H]+, 382.0437; found, 382.0440. 9-Acetyl-7-chloro-2-phenyl-2,3-dihydro-1H-carbazol4(9H)-one (3af). Petroleum ether/ethyl acetate 8:1; yield 84% (141 mg, 0.42 mmol); white solid; mp 180−182 °C; 1H NMR (300 MHz, CDCl3): δ 8.26 (d, J = 8.4 Hz, 1H), 7.94 (s, 1H), 7.39−7.31 (m, 6H), 3.64−3.54 (m, 2H), 3.40−3.30 (m, 1H), 2.98−2.85 (m, 2H), 2.76 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 194.1, 169.8, 150.6, 142.4, 136.2, 131.2, 128.9, 127.4, 126.8, 125.2, 124.3, 122.6, 117.3, 115.0, 44.5, 42.0, 34.4, 27.4; IR (KBr) ν: 3467, 1712, 1662, 1607, 1550, 1466, 1366, 1288, 1270, 1197, 1126, 1033, 996, 798 cm−1; HRMS (APCI): calcd for [C21H16ClNO2 + H]+, 372.1206; found, 372.1207. 9-Acetyl-6-fluoro-2-phenyl-2,3-dihydro-1H-carbazol4(9H)-one (3ag). Petroleum ether/ethyl acetate 8:1; yield 89% (143 mg, 0.45 mmol); white solid; mp 109−111 °C; 1H NMR (300 MHz, CDCl3): δ 8.01−7.99 (m, 1H), 7.88−7.84 (m, 1H), 7.41−7.31 (m, 5H), 7.09−7.03 (m, 1H), 3.64−6.52 (m, 2H),

3.38−3.28 (m, 1H), 2.94−2.82 (m, 2H), 2.74 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 194.0, 169.9, 160.2 (d, JC−F = 240.7 Hz), 142.4, 132.2, 128.9, 127.4, 126.8, 115.7 (d, JC−F = 9.0 Hz), 112.9 (d, JC−F = 24.7 Hz), 107.7 (d, JC−F = 24.7 Hz), 44.4, 42.0, 34.4, 27.3; IR (KBr) ν: 3312, 1719, 1667, 1635, 1548, 1457, 1398, 1366, 1295, 1254, 1133, 1046, 1005, 773, 700 cm−1; HRMS (APCI): calcd for [C20H16FNO2 + H]+, 322.1238; found, 322.1242. 9-Acetyl-6-chloro-2-phenyl-2,3-dihydro-1H-carbazol4(9H)-one (3ah). Petroleum ether/ethyl acetate 8:1; yield 88% (148 mg, 0.44 mmol); white solid; mp 144−146 °C; 1H NMR (300 MHz, CDCl3): δ 8.23 (s, 1H), 7.77 (d, J = 9.0 Hz, 1H), 7.41−7.31 (m, 6H), 7.23 (d, J = 9.0 Hz, 1H), 3.57−3.51 (m, 2H), 3.30−3.20 (m, 1H), 2.88−2.79 (m, 2H), 2.68 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 194.1, 170.3, 150.7, 141.2, 134.6, 133.8, 132.9, 128.9, 128.3, 126.4, 126.1, 122.0, 117.2, 113.9, 44.5, 41.2, 34.1, 27.4, 21.2; IR (KBr) ν: 3425, 1725, 1680, 1636, 1525, 1495, 1458, 1383, 1341, 1296, 1252, 1011, 817, 785, 756, 641 cm−1; HRMS (APCI): calcd for [C20H16ClNO2 + H]+, 338.0942; found, 338.0937. 8511

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ACS Omega

H NMR (300 MHz, CDCl3): δ 8.28 (d, J = 7.8 Hz, 1H), 7.52 (d, J = 7.8 Hz, 1H), 7.34 (d, J = 8.1 Hz, 2H), 7.26−7.23 (m, 3H), 3.63−3.56 (m, 1H), 3.34−3.27 (m, 1H), 3.18−3.08 (m, 1H) 2.85−2.82 (m, 2H), 2.70 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 192.8, 172.4, 150.2, 140.7, 134.4, 133.1, 129.1, 129.0, 128.4, 128.1, 125.9, 121.2, 106.0, 44.8, 40.9, 31.1, 30.2; IR (KBr) ν: 3423, 1726, 1649, 1566, 1535, 1456, 1422, 1391, 1346, 1263, 1163, 1119, 788, 756, 701 cm−1; HRMS (APCI): calcd for [C20H15BrClNO2 + H]+, 416.0047; found, 416.0043. 9-Acetyl-7-chloro-2-(4-chlorophenyl)-2,3-dihydro-1H-carbazol-4(9H)-one (3bf). Petroleum ether/ethyl acetate 8:1; yield 81% (150 mg, 0.41 mmol); white solid; mp 165−167 °C; 1 H NMR (300 MHz, CDCl3): δ 8.23 (d, J = 8.4 Hz, 1H), 7.87 (s, 1H), 7.34 (d, J = 8.1 Hz, 3H), 7.25 (d, J = 8.1 Hz, 2H), 3.63−3.50 (m, 2H), 3.34−3.24 (m, 1H), 2.90−2.79 (m, 2H), 2.76 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 193.6, 169.8, 150.5, 140.9, 136.1, 133.1, 131.3, 129.0, 128.2, 125.3, 122.6, 117.2, 114.8, 44.3, 41.3, 34.2, 27.4; IR (KBr) ν: 3435, 1721, 1673, 1546, 1493, 1470, 1409, 1368, 1331, 1274, 1169, 1012, 821, 613 cm−1; HRMS (APCI): calcd for [C20H15ClNO2 + H]+, 372.0553; found, 372.0553. 9-Acetyl-2-(4-chlorophenyl)-6-fluoro-2,3-dihydro-1H-carbazol-4(9H)-one (3bg). Petroleum ether/ethyl acetate 8:1; yield 90% (160 mg, 0.45 mmol); white solid; mp 137−139 °C; 1 H NMR (300 MHz, CDCl3): δ 8.04−8.01 (m, 1H), 7.85−7.81 (m, 1H), 7.35 (d, J = 8.1 Hz, 2H), 7.27−7.26 (m, 3H), 7.13− 7.09 (m, 1H), 3.68−3.52 (m, 2H), 3.38−3.29 (m, 1H), 2.94− 2.82 (m, 2H), 2.78 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 193.6, 169.9, 160.3 (d, JC−F = 242.25 Hz), 151.3, 140.9, 133.1, 132.1, 129.0, 128.2, 127.1 (d, JC−F = 10.5 Hz), 115.5 (d, JC−F = 9.0 Hz), 113.0 (d, JC−F = 25.5 Hz), 107.9 (d, JC−F = 24.5 Hz), 44.3, 41.3, 34.3, 27.4; IR (KBr) ν: 3458, 1719, 1664, 1637, 1553, 1500, 1466, 1441, 1395, 1366, 1279, 1258, 1197, 1131, 1028, 987, 832, 800, 786 cm−1; HRMS (APCI): calcd for [C21H15FClNO2 + H]+, 356.0848; found, 356.0850. 9-Acetyl-6-chloro-2-(4-chlorophenyl)-2,3-dihydro-1H-carbazol-4(9H)-one (3bh). Petroleum ether/ethyl acetate 8:1; yield 87% (162 mg, 0.44 mmol); white solid; mp 177−179 °C; 1 H NMR (300 MHz, CDCl3): δ 8.34 (s, 1H), 7.79 (d, J = 9.0 Hz, 1H), 7.36−7.31 (m, 3H), 7.27−7.24 (m, 2H), 3.67−3.51 (m, 2H), 3.37−3.28 (m, 1H), 2.93−2.82 (m, 2H), 2.78 (s, 3H); 13 C NMR (75 MHz, CDCl3): δ 193.9, 169.8, 151.1, 142.4, 134.2, 130.4, 128.9, 127.4, 126.9, 125.2, 121.2, 116.7, 115.8, 44.3, 41.9, 34.3, 27.3; IR (KBr) ν: 3412, 1717, 1660, 1553, 1496, 1448, 1393, 1361, 1336, 1277, 1261, 1133, 1069, 989, 834, 800, 668, 599 cm −1 ; HRMS (APCI): calcd for [C20H15Cl2NO2 + H]+, 372.0553; found, 372.0550. 9-Acetyl-6-bromo-2-(4-chlorophenyl)-2,3-dihydro-1H-carbazol-4(9H)-one (3bi). Petroleum ether/ethyl acetate 8:1; yield 88% (183 mg, 0.44 mmol); white solid; mp 170−172 °C; 1H NMR (300 MHz, CDCl3): δ 8.48 (s, 1H), 7.73 (d, J = 8.7 Hz, 1H), 7.45 (d, J = 8.7 Hz, 1H), 7.35 (d, J = 8.7 Hz, 2H), 7.26 (d, J = 7.8 Hz, 2H), 3.66−3.51 (m, 2H), 3.36−3.27 (m, 1H), 2.91−2.81 (m, 2H), 2.77 (s, 3H); 13C NMR (75 MHz CDCl3): δ 193.5, 169.8, 150.9, 140.8, 134.5, 133.1, 129.1, 128.2, 128.2, 127.4, 124.6, 118.4, 116.8, 115.8, 44.3, 41.3, 34.2, 27.4; IR (KBr) ν: 3444, 1717, 1664, 1653, 1557, 1496, 1468, 1366, 1336, 1277, 1199, 1135, 992, 830, 796, 606 cm−1; HRMS (APCI): calcd for [C20H15BrClNO2 + H]+, 416.0047; found, 416.0042. 9-Acetyl-2-(4-chlorophenyl)-6-(trifluoromethyl)-2,3-dihydro-1H-carbazol-4(9H)-one (3bj). Petroleum ether/ethyl 1

9-Acetyl-6-bromo-2-phenyl-2,3-dihydro-1H-carbazol4(9H)-one (3ai). Petroleum ether/ethyl acetate 8:1; yield 87% (166 mg, 0.43 mmol); white solid; mp 145−147 °C; 1H NMR (300 MHz, CDCl3): δ 8.42 (s, 1H), 7.74 (d, J = 8.7 Hz, 1H), 7.39−7.31 (m, 6H), 3.59−3.50 (m, 2H), 3.33−3.23 (m, 1H), 2.91−2.79 (m, 2H), 2.71 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 193.9, 169.8, 151.0, 142.4, 134.5, 128.9, 128.0, 127.4, 126.9, 124.3, 118.2, 116.8, 116.1, 44.4, 41.9, 34.3, 27.4; IR (KBr) ν: 3449, 1735, 1664, 1616, 1555, 1480, 1332, 1242, 1195, 1151, 1028, 777, 759, 691 cm−1; HRMS (APCI): calcd for [C20H16BrNO2 + H ]+, 382.0437; found, 382.0442. 9-Acetyl-2-phenyl-6-(trifluoromethyl)-2,3-dihydro-1H-carbazol-4(9H)-one (3aj). Petroleum ether/ethyl acetate 8:1; yield 87% (161 mg, 0.44 mmol); white solid; mp 128−130 °C; 1H NMR (300 MHz, CDCl3): δ 8.62 (s, 1H), 8.00 (d, J = 8.7 Hz, 1H), 7.58 (d, J = 8.4 Hz, 1H), 7.39−7.31 (m, 5H), 3.66−3.54 (m, 2H), 3.41−3.31 (m, 1H), 2.97−2.85 (m, 2H), 2.78 (s, 3H); 13 C NMR (75 MHz, CDCl3): δ 193.9, 169.9, 151.6, 142.3, 137.4, 129.0, 126.8, 125.7, 122.1 (q, JC−F = 3.7 Hz), 119.3 (q, JC−F = 3.7 Hz), 117.3, 114.9, 44.4, 41.9, 34.3, 27.4; IR (KBr) ν: 3439, 1721, 1662, 1548, 1491, 1452, 1409, 1366, 1338, 1284, 1182, 1014, 839, 773, 707 cm−1; HRMS (APCI): calcd for [C21H16F3NO2 + H]+, 372.1206; found, 372.1207. 1,1′-(4-Oxo-2-phenyl-3,4-dihydro-1H-carbazole-6,9(2H)diyl)diethanone (3ak). Petroleum ether/ethyl acetate 8:1; yield 85% (146 mg, 0.43 mmol); white solid; mp 201−203 °C; 1H NMR (300 MHz, CDCl3): δ 8.92 (s, 1H), 8.05 (d, J = 8.7 Hz, 1H), 7.94 (d, J = 9.0 Hz, 1H), 7.42−7.39 (m, 6H), 3.71−3.57 (m, 2H), 3.45−3.36 (m, 1H), 2.97−2.89 (m, 2H), 2.83 (s, 3H), 2.72 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 197.9, 194.2, 170.0, 151.8, 142.4, 138.2, 133.8, 128.9, 127.4, 126.8, 125.8, 125.1, 123.1, 117.6, 114.4, 44.5, 41.9, 34.3, 27.5, 26.8; IR (KBr) ν: 3458, 1740, 1667, 1612, 1557, 1480, 1363, 1318, 1245, 1151, 1028, 989, 784, 759, 695, 531 cm−1; HRMS (APCI): calcd for [C22H19NO3 + H]+, 346.1438; found, 346.1438. 9-Acetyl-2-(4-chlorophenyl)-2,3-dihydro-1H-carbazol4(9H)-one (3ba). Petroleum ether/ethyl acetate 8:1; yield 89% (150 mg, 0.45 mmol); white solid; mp 171−173 °C; 1H NMR (300 MHz, CDCl3): δ 8.36 (d, J = 8.7 Hz, 1H), 7.81 (d, J = 9.0 Hz, 1H), 7.39−7.33 (m, 4H), 7.27−7.25 (m, 2H), 3.70−3.62 (m, 1H), 3.59−3.51 (m, 1H), 3.38−3.29 (m, 1H), 2.93−2.83 (m, 2H), 2.80 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 194.0, 170.3, 150.6, 141.1, 135.6, 132.9, 129.0, 128.2, 125.9, 125.3, 124.8, 122.1, 117.5, 114.1, 44.5, 41.3, 34.1, 27.5; IR (KBr) ν: 3417, 1714, 1662, 1559, 1493, 1457, 1365, 1334, 1270, 1206, 1181, 1062, 992, 827, 743, 606, 588 cm−1; HRMS (APCI): calcd for [C20H16ClNO2 + H]+, 338.0942; found, 338.0943. 9-Acetyl-2-(4-chlorophenyl)-6-methyl-2,3-dihydro-1H-carbazol-4(9H)-one (3bc). Petroleum ether/ethyl acetate 8:1; yield 83% (146 mg, 0.42 mmol); white solid; mp 202−204 °C; 1 H NMR (300 MHz, CDCl3): δ 8.15 (s, 1H), 7.66 (d, J = 8.4 Hz, 1H), 7.33 (d, J = 8.4 Hz, 2H), 7.25−7.18 (m, 2H), 7.16 (d, J = 8.4 Hz, 2H), 3.63−3.49 (m, 2H), 3.31−3.21 (m, 1H), 2.87−2.78 (m, 2H), 2.75 (s, 3H), 2.46 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 194.5, 170.6, 151.1, 141.5, 135.1, 134.2, 133.2, 129.3, 128.6, 126.8, 122.4, 117.7, 114.1, 44.9, 41.6, 34.5, 27.8, 21.5; IR (KBr) ν: 3444, 1710, 1664, 1607, 1550, 1493, 1455, 1398, 1343, 1293, 1220, 1005, 832, 805, 638 cm−1; HRMS (APCI): calcd for [C21H18ClNO2 + H]+, 352.1099; found, 352.1096. 9-Acetyl-8-bromo-2-(4-chlorophenyl)-2,3-dihydro-1H-carbazol-4(9H)-one (3be). Petroleum ether/ethyl acetate 8:1; yield 75% (156 mg, 0.43 mmol); white solid; mp 172−174 °C; 8512

DOI: 10.1021/acsomega.7b01637 ACS Omega 2017, 2, 8507−8516

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ACS Omega

8.34 (d, J = 8.7 Hz, 1H), 7.85 (d, J = 8.7 Hz, 1H), 7.37−7.34 (m, 2H), 3.31 (t, J = 6.3 Hz, 2H), 2.81 (s, 3H), 2.61 (t, J = 6.3 Hz, 2H), 2.29−2.21 (m, 2H); 13C NMR (75 MHz, CDCl3): δ 195.7, 170.4, 151.7, 135.4, 126.2, 125.0, 124.7, 122.1, 117.6, 114.2, 37.8, 27.5, 26.3, 23.5; IR (KBr) ν: 3439, 1721, 1655, 1646, 1563, 1553, 1482, 1411, 1361, 1281, 1174, 1035, 939, 900, 764, 748 cm−1; HRMS (APCI): calcd for [C14H13NO2 + H]+, 228.1019; found, 228.1023. 9-Acetyl-6-(tert-butyl)-2,3-dihydro-1H-carbazol-4(9H)-one (3dd). Petroleum ether/ethyl acetate 6:1; yield 69% (97 mg, 0.35 mmol); white solid; mp 110−112 °C; 1H NMR (300 MHz, CDCl3): δ 8.36 (s, 1H), 7.75 (d, J = 8.7 Hz, 1H), 7.40 (d, J = 8.7 Hz, 1H), 3.29 (t, J = 6.0 Hz, 2H), 2.79 (s, 3H), 2.59 (t, J = 6.0 Hz, 2H), 2.26−2.18 (m, 2H), 1.39 (s, 9H); 13C NMR (75 MHz, CDCl3): δ 195.8, 170.3, 152.0, 148.0, 133.5, 126.3, 122.6, 118.4, 113.7, 37.9, 31.6, 27.4, 26.4, 23.5; IR (KBr) ν: 3426, 1721, 1662, 1651, 1550, 1477, 1461, 1400, 1363, 1286, 1174, 1031, 998, 905, 827, 611 cm−1; HRMS (APCI): calcd for [C18H21NO2 + H]+, 284.1645; found, 284.1647. 9-Acetyl-2,2-dimethyl-2,3-dihydro-1H-carbazol-4(9H)-one (3ea). Petroleum ether/ethyl acetate 8:1; yield 81% (103 mg, 0.41 mmol); white solid; mp 132−134 °C; 1H NMR (300 MHz, CDCl3): δ 8.28 (d, J = 8.4 Hz, 1H), 7.80 (d, J = 8.7 Hz, 1H), 7.33−7.30 (m, 2H), 3.11 (s, 2H), 2.76 (s, 3H), 2.41 (s, 2H), 1.13 (s, 6H); 13C NMR (75 MHz, CDCl3): δ 195.5, 170.8, 150.7, 136.1, 126.4, 125.3, 124.9, 122.2, 116.9, 114.7, 52.0, 40.6, 35.5, 29.0, 27.9; IR (KBr) ν: 3403, 1724, 1709, 1651, 1621, 1557, 1484, 1443, 1352, 1295, 1272, 1176, 1140, 1071, 1010, 939, 768, 752, 679, 654 cm−1; HRMS (APCI): calcd for [C16H17NO2 + H]+, 256.1332; found, 256.1331. 9-Acetyl-2,2,6-trimethyl-2,3-dihydro-1H-carbazol-4(9H)one (3ec). Petroleum ether/ethyl acetate 8:1; yield 83% (111 mg, 0.42 mmol); white solid; mp 120−122 °C; 1H NMR (300 MHz, CDCl3): δ 8.13 (s, 1H), 7.69 (d, J = 8.7 Hz, 1H), 7.16 (d, J = 8.4 Hz, 1H), 3.17 (s, 2H), 2.80 (s, 2H), 2.47 (s, 3H), 1.17 (s, 6H) m; 13C NMR (75 MHz, CDCl3): δ 195.7, 170.8, 151.0, 134.8, 134.3, 126.6, 126.5, 122.3, 116.8, 114.3, 52.1, 40.7, 35.5, 27.9, 21.5; IR (KBr) ν: 3467, 1712, 1662, 1553, 1459, 1402, 1366, 1345, 1299, 1190, 1069, 998, 818, 631 cm−1; HRMS (APCI): calcd for [C17H19NO2 + H]+, 270.1489; found, 270.1485. 9-Acetyl-6-(tert-butyl)-2,2-dimethyl-2,3-dihydro-1H-carbazol-4(9H)-one (3ed). Petroleum ether/ethyl acetate 8:1; yield 86% (134 mg, 0.43 mmol); white solid; mp 73−75 °C; 1H NMR (300 MHz, CDCl3): δ 8.35 (s, 1H), 7.73 (d, J = 8.7 Hz, 1H), 7.41 (d, J = 8.7 Hz, 1H), 3.18 (s, 1H), 2.80 (s, 3H), 2.47 (s, 2H), 1.39 (s, 9H), 1.17 (s, 6H); 13C NMR (75 MHz, CDCl3): δ 195.4, 170.4, 150.7, 148.0, 133.7, 126.1, 122.6, 118.3, 116.7, 113.7, 51.8, 40.3, 35.1, 34.7, 31.6, 28.6, 27.5; IR (KBr) ν: 3444, 1717, 1655, 1553, 1468, 1363, 1297, 1258, 1190, 1144, 1008, 903, 825, 622 cm−1; HRMS (APCI): calcd for [C20H25NO2 + H]+, 312.1958; found, 312.1956. 2-Phenyl-9-propionyl-2,3-dihydro-1H-carbazol-4(9H)-one (3am). Petroleum ether/ethyl acetate 8:1; yield 86% (136 mg, 0.43 mmol); white solid; mp 158−160 °C; 1H NMR (300 MHz, CDCl3): δ 8.43−8.29 (m, 1H), 7.86−7.84 (m, 1H), 7.44−7.26 (m, 7H), 3.71−3.54 (m, 2H), 3.45−3.36 (m, 1H), 3.08 (q, J = 6.3 Hz, 2H), 2.99−2.82 (m, 2H), 1.36 (t, J = 6.3 Hz, 3H); 13C NMR (75 MHz, CDCl3): δ 194.4, 174.4, 150.9, 142.7, 135.5, 128.8, 127.2, 126.9, 126.0, 125.1, 124.6, 122.1, 114.4, 44.6, 42.0, 34.5, 32.7, 8.9; IR (KBr) ν: 3458, 1730, 1653, 1637, 1600, 1548, 1484, 1450, 1413, 1345, 1249, 1135, 1053,

acetate 8:1; yield 85% (172 mg, 0.43 mmol); white solid; mp 146−148 °C; 1H NMR (300 MHz, CDCl3): δ 8.61 (s, 1H), 7.96 (d, J = 8.7 Hz, 1H), 7.59 (d, J = 8.7 Hz, 1H), 7.34 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.1 Hz, 2H), 3.67−3.54 (m, 2H), 3.38−3.29 (m, 1H), 2.92−2.82 (m, 2 H), 2.80 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 193.5, 169.9, 151.5, 140.7, 137.3, 133.1, 129.1, 128.2, 126.9, 126.1, 125.7, 122.1 (q, JC−F = 3.7 Hz), 119.4 (q, JC−F = 3.7 Hz), 117.2, 114.7, 44.3, 41.3, 34.1, 27.4; IR (KBr) ν: 3403, 1828, 1716, 1667, 1557, 1493, 1482, 1461, 1366, 1325, 1274, 1178, 1115, 1060, 1001, 825, 725 cm−1; HRMS (APCI): calcd for [C21H15ClF3NO2 + H]+, 405.0816; found, 405.0815. 9-Acetyl-2-methyl-2,3,9,9a-tetrahydro-1H-carbazol-4(4aH)-one (3ca). Petroleum ether/ethyl acetate 8:1; yield 74% (120 mg, 0.37 mmol); white solid; mp 109−111 °C; 1H NMR (300 MHz, CDCl3): δ 8.34 (d, J = 8.7 Hz, 1H), 7.84 (d, J = 9.0 Hz, 1H), 7.37−7.34 (m, 2H), 3.49−3.42 (m, 1H), 2.96−2.87 (m, 1H), 2.82 (s, 3H), 2.66−2.61 (m, 1H), 2.42−2.33 (m, 2H), 1.23 (d, J = 6.0 Hz, 3H); 13C NMR (75 MHz, CDCl3): δ 195.8, 170.8, 151.7, 136.0, 126.5, 125.4, 125.0, 122.4, 117.8, 114.6, 46.5, 34.8, 31.7, 27.9, 21.7; IR (KBr) ν: 3459, 1721, 1664, 1651, 1598, 1559, 1482, 1434, 1363, 1284, 1213, 1181, 1001, 996, 773, 739, 588 cm−1; HRMS (APCI): calcd for [C15H15NO2 + H]+, 242.1176; found, 242.1172. 9-Acetyl-2,7-dimethyl-2,3-dihydro-1H-carbazol-4(9H)-one (3cb). Petroleum ether/ethyl acetate 8:1; yield 69% (88 mg, 0.35 mmol); white solid; mp 112−114 °C; 1H NMR (300 MHz, CDCl3): δ 8.17 (d, J = 8.1 Hz, 1H), 7.65 (s, 1H), 7.18 (d, J = 7.8 Hz, 1H), 3.44−3.36 (m, 1H), 2.91−2.82 (m, 1H), 2.79 (s, 3H), 2.62−2.57 (m, 1H), 2.48 (s, 3H). 2.38−2.29 (m, 2H), 1.21 (d, J = 6.0 Hz, 3H); 13C NMR (75 MHz, CDCl3): δ 195.4, 170.4, 150.7, 136.1, 135.0, 125.9, 123.7, 121.5, 117.4, 114.6, 46.0, 34.4, 31.4, 27.5, 22.1, 21.3; IR (KBr) ν: 3439, 1717, 1665, 1660, 1562, 1548, 1493, 1416, 1363, 1334, 1281, 1201, 1191, 830, 818, 645 cm−1, HRMS (APCI): calcd for [C16H17NO2 + H]+, 256.1332; found, 256.1336. 9-Acetyl-6-(tert-butyl)-2-methyl-2,3-dihydro-1H-carbazol4(9H)-one (3cd). Petroleum ether/ethyl acetate 8:1; yield 76% (113 mg, 0.38 mmol); white solid; mp 73−75 °C; 1H NMR (300 MHz, CDCl3): δ 8.35 (s, 1H), 7.73 (d, J = 8.7 Hz, 1H), 7.40 (d, J = 8.7 Hz, 1H), 3.44−3.37 (m, 1H), 2.88−2.82 (m, 1H), 2.77 (s, 3H), 2.61−2.56 (m, 1H), 2.36−2.27 (m, 2H), 1.39 (s, 9H), 1.19 (d, J = 6.3 Hz, 3H); 13C NMR (75 MHz, CDCl3): δ 195.5, 170.3, 151.5, 148.0, 133.7, 126.1, 122.7, 118.3, 117.4, 113.8, 46.1, 34.7, 34.4, 31.6, 27.4, 21.2; IR (KBr) ν: 3444, 1717, 1655, 1553, 1468, 1363, 1297, 1258, 1190, 1144, 1008, 903, 825, 622 cm−1; HRMS (APCI): calcd for [C20H25NO2 + H]+, 312.1958; found, 312.1956. 9-Acetyl-6-methoxy-2-methyl-2,3-dihydro-1H-carbazol4(9H)-one (3cl). Petroleum ether/ethyl acetate 8:1; yield 65% (88 mg, 0.32 mmol); white solid; mp 168−170 °C; 1H NMR (300 MHz, CDCl3): δ 7.82 (s, 1H), 7.74 (d, J = 9.0 Hz, 1H), 6.93 (d, J = 9.0 Hz, 1H), 3.89 (s, 3H), 3.46−3.39 (m, 1H), 2.92−2.82 (m, 1H), 2.77 (s, 3H), 2.63−2.59 (m, 1H), 2.39− 2.30 (m, 2H), 1.22 (d, J = 6.0 Hz, 3H); 13C NMR (75 MHz, CDCl3): δ 195.9, 170.5, 157.6, 151.9, 130.5, 127.6, 117.7, 115.6, 114.4, 104.3, 56.1, 46.4, 34.9, 31.7, 27.7, 21.6; IR (KBr) ν: 3444, 1733, 1712, 1662, 1598, 1549, 1464, 1441, 1356, 1281, 1167, 1053, 1003, 880, 764, 691 cm−1; HRMS (APCI): calcd for [C16H17NO3 + H]+, 271.1281; found, 272.1279. 9-Acetyl-2,3-dihydro-1H-carbazol-4(9H)-one (3da). Petroleum ether/ethyl acetate 6:1; yield 68% (77 mg, 0.34 mmol); white solid; mp 116−118 °C; 1H NMR (300 MHz, CDCl3): δ 8513

DOI: 10.1021/acsomega.7b01637 ACS Omega 2017, 2, 8507−8516

Article

ACS Omega 955, 880, 818, 759, 701 cm−1; HRMS (APCI): calcd for [C21H19NO2 + H]+, 318.1489; found, 318.1487. 2-Methyl-9-propionyl-2,3,9,9a-tetrahydro-1H-carbazol-4(4aH)-one (3cm). Petroleum ether/ethyl acetate 8:1; yield 76% (97 mg, 0.38 mmol); white solid; mp 128−130 °C; 1H NMR (300 MHz, CDCl3): δ 8.33 (d, J = 8.7 Hz, 1H), 7.83 (d, J = 8.7 Hz, 1H), 7.35−7.33 (m, 2H), 3.49−3.41 (m, 1H), 3.09 (q, J = 6.9 Hz, 2H), 2.96−2.87 (m, 1H), 2.64−2.60 (m, 1H), 2.40− 2.31 (m, 2H), 1.38 (t, J = 6.9 Hz, 3H), 1.22 (d, J = 6.0 Hz, 3H); 13 C NMR (75 MHz, CDCl3): δ 195.4, 174.5, 151.5, 135.4, 126.1, 124.9, 124.5, 121.9, 117.2, 114.3, 46.1, 34.6, 32.7, 31.3, 21.3, 8.9; IR (KBr) ν: 3449, 1730, 1651, 1639, 1600, 1559, 1548, 1484, 1450, 1407, 1345, 1254, 1138, 1051, 1017, 953, 882, 825, 759, 702, 536 cm−1; HRMS (APCI): calcd for [C16H17NO2 + H]+, 256.1332; found, 256.1333. 2-Methyl-9-(2-phenylacetyl)-2,3-dihydro-1H-carbazol4(9H)-one (3cn). Petroleum ether/ethyl acetate 8:1; yield 73% (115 mg, 0.36 mmol); white solid; mp 142−144 °C; 1H NMR (300 MHz, CDCl3): δ 8.34 (d, J = 7.5 Hz, 1H), 7.87 (d, J = 7.5 Hz, 1H), 7.40−7.26 (m, 7H), 4.41 (m, 2H), 3.45−3.38 (m, 1H), 2.94−2.85 (m, 1H), 2.64−2.60 (m, 1H), 2.40−2.31 (m, 2H), 1.18 (d, J = 5.7 Hz, 1H); 13C NMR (75 MHz, CDCl3): δ 195.4, 171.8, 151.5, 135.4, 132.6, 129.4, 128.9, 127.7, 126.2, 125.1, 124.7, 122.1, 117.5, 114.2, 46.1, 45.4, 34.4, 31.3, 21.2; IR (KBr) ν: 3408, 1719, 1653, 1605, 1555, 1484, 1445, 1416, 1350, 1325, 1264, 1142, 1097, 1053, 939, 766, 702 cm−1; HRMS (APCI): calcd for [C22H21NO2 + H]+, 332.1645; found, 332.1642. 2,2-Dimethyl-9-propionyl-2,3-dihydro-1H-carbazol-4(9H)one (3em). Petroleum ether/ethyl acetate 8:1; yield 86% (115.81 mg, 0.43 mmol); white solid; mp 94−96 °C; 1H NMR (300 MHz, CDCl3): δ 8.32 (d, J = 8.7 Hz, 1H), 7.82 (d, J = 8.4 Hz, 1H), 7.35−7.33 (m, 2H), 3.19 (s, 2H), 3.09 (q, J = 6.9 Hz, 2H), 2.47 (s, 2H), 1.38 (t, J = 6.9 Hz, 3H), 1.16 (s, 6H); 13C NMR (75 MHz, CDCl3): δ 195.3, 174.6, 150.6, 135.5, 126.1, 124.8, 124.5, 122.0, 116.5, 114.3, 51.7, 40.4, 32.8, 28.6, 8.8; IR (KBr) ν: 3408, 1728, 1712, 1661, 1557, 1484, 1450, 1416, 1402, 1354, 1314, 1293, 1272, 1179, 1069, 1008, 766, 754, 677, 672 cm−1; HRMS (APCI): calcd for [C17H19NO2 + H]+, 270.1489; found, 270.1484. 2,2-Dimethyl-9-(2-phenylacetyl)-2,3-dihydro-1H-carbazol4(9H)-one (3en). Petroleum ether/ethyl acetate 8:1; yield 78% (129 mg, 0.39 mmol); white solid; mp 165−167 °C; 1H NMR (300 MHz, CDCl3): δ 8.35 (d, J = 8.4 Hz, 1H), 7.87 (d, J = 8.4 Hz, 1H), 7.38−7.35 (m, 5H), 7.29−7.26 (m, 2H), 4.42 (s, 2H), 3.15 (s, 2H), 2.47 (s, 2H), 1.13 (s, 6H); 13C NMR (75 MHz, CDCl3): δ 195.1, 171.9, 150.6, 135.5, 132.6, 129.3, 128.9, 127.7, 126.2, 125.0, 124.7, 122.1, 116.6, 114.2, 51.7, 45.4, 40.1, 35.1, 28.5, 28.0; IR (KBr) ν: 3411, 1715, 1661, 1609, 1573, 1456, 1445, 1421, 1369, 1386, 1264, 1142, 1097, 1053, 10025, 768, 705 cm−1; HRMS (APCI): calcd for [C21H25NO2 + H]+, 324.1958; found, 342.1961. 9-(Cyclohexanecarbonyl)-2,2-dimethyl-2,3-dihydro-1Hcarbazol-4(9H)-one (3eo). Petroleum ether/ethyl acetate 8:1; yield 81% (131 mg, 0.41 mmol); white solid; mp 88−90 °C; 1H NMR (300 MHz, CDCl3): δ 8.31 (d, J = 8.7 Hz, 1H), 7.63 (d, J = 8.7 Hz, 1H), 7.35−7.26 (m, 2H), 3.28−3.22 (m, 1H), 3.08 (s, 2H), 2.47 (s, 2H) 2.05−2.01 (m, 2H), 1.90−1.88 (m, 3H), 1.78−7.65 (m, 3H), 1.46−1.35 (m, 3H), 1.15 (s, 6H); 13C NMR (75 MHz, CDCl3): δ 195.0, 177.6, 150.5, 135.4, 126.0, 124.7, 124.3, 122.0, 115.9, 113.3, 51.8, 46.0, 39.7, 35.2, 29.3, 28.6, 25.5, 25.4; IR (KBr) ν: 3408, 1717, 1655, 1603, 1553, 1484, 1354, 1347, 1256, 1144, 1126, 1087, 998, 750, 593 cm−1;

HRMS (APCI): calcd for [C21H25NO2 + H]+, 324.1958; found, 324.1961. 2,2-Dimethyl-2,3-dihydro-1H-carbazol-4(9H)-one (4ea). Petroleum ether/ethyl acetate 6:1; yield 95% (101 mg, 0.48 mmol); white solid; mp 94−96 °C; 1H NMR (300 MHz, CDCl3): δ 9.73 (s, 1H), 8.20 (d, J = 8.1 Hz, 1H), 7.38 (d, J = 8.1 Hz, 1H), 7.24−7.21 (m, 2H), 2.83 (s, 2H), 2.47 (s, 2H), 1.14 (s, 6H); 13C NMR (75 MHz, CDCl3): δ 194.1, 151.1, 136.2, 124.6, 123.1, 122.4, 121.1, 111.3, 52.2, 37.3, 35.7, 28.6; IR (KBr) ν: 3421, 1728, 1707, 1655, 1623, 1555, 1480, 1448, 1420, 1351, 1341, 1181, 1069, 1021, 998, 941, 769, 754, 675 cm−1; HRMS (APCI): calcd for [C14H17NO + H]+, 215.1323; found, 215.1325.

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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/acsomega.7b01637. Copies of 1H and 13C NMR spectra of all compounds (PDF) X-ray data for compound 3ea and 3cn (CIF) Crystallographic data (CIF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected] (Y.S.). ORCID

Xinwei He: 0000-0002-1974-2464 Yongjia Shang: 0000-0001-9873-9150 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the National Natural Science Foundation of China (nos. 21772001, 21372008), the Natural Science Foundation of Education Administration of Anhui Province (no. KJ2016A267), and the Special and Excellent Research Fund of Anhui Normal University.

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REFERENCES

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DOI: 10.1021/acsomega.7b01637 ACS Omega 2017, 2, 8507−8516