Three-Component Cascade Synthesis of Carbazoles through [1s,6s

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Three-Component Cascade Synthesis of Carbazoles through [1s,6s] Sigmatropic Shift under Metal-Free Conditions Shanping Chen, Pingyu Jiang, Pu Wang, Yong Pei, Huawen Huang, Fuhong Xiao, and Guo-Jun Deng J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 20 Feb 2019 Downloaded from http://pubs.acs.org on February 20, 2019

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The Journal of Organic Chemistry

Three-Component Cascade Synthesis of Carbazoles through [1s,6s] Sigmatropic Shift under Metal-Free Conditions

Shanping Chen*, Pingyu Jiang, Pu Wang, Yong Pei, Huawen Huang, Fuhong Xiao, Guo-Jun Deng*

Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan 411105, China, Fax: (+86)-731-58292251

ABSTRACT: A novel method was developed for the synthesis of substituted carbazoles from commercially available starting materials under metal-free conditions. This strategy involves a [1s,6s] sigmatropic shift step and introduces an electron-withdrawing ester substituent at the C2 position of the carbazole ring. The present protocol afforded the desired carbazole derivatives with good regioselectivity and well functional group tolerance. And DFT calculations were carried out to support the reaction pathway. INTRODUCTION

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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

Carbazoles are fused N-heterocycles, many of which have unique pharmacological and biological activities and thus have wide applications in medicinal chemistry.1 In addition, carbazoles have been widely used in materials science especially as organic light-emitting diodes (OLED) as a result of their good electron-optical properties.2 Due to the importance of carbazoles in these fields, a series of methods for the synthesis of these compounds have been developed during the past several decades.3-6 Among them, the indole-to-carbazole strategy represents an efficient approach for carbazole synthesis since it starts from simple substrates without pre-functionalization and offers convenient opportunities to achieve desirable synthetic convergence and function-installing flexibility. Generally, the indole-to-carbazole process mainly includes three approaches: (i) with the assistance of the transition-metal (TM) catalyst, such as palladium, rhodium, manganese and gold, indoles react with two molecules of alkynes7 or alkenes8 through [2+2′+2′] annulation to produce substituted carbazoles (Scheme 1a); (ii) indoles without prefunctionalization react with highly reactive coupling partners such as 1,4-dicarbonyl compounds,9 or their alkyne-derivatives,10 allene-derivatives11 and dihydrofuran12 through [2+4] annulation to afford the carbazole products; (iii) 2,3-unsubstituted indoles couple with two different molecules through [2+2′+2″] annulation to give unsymmetrical carbazoles derivatives under TM-free conditions.13 Among these strategies, the third approach is the most attractive method for carbazole synthesis since different substituents can be introduced in one-pot under TM-free conditions. Scheme 1. Indole-to-Carbazole Transformation.


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In recent years, we focused on indole-template synthesis through direct functionalization to synthesize complex indole-based heterocycles.14 Several three-component approaches for carbazole synthesis from commercially available indoles, ketones and alkenes have been developed.15 The three components could be orderly assembled via formal [2+2'+2"] annulation process to provide the corresponding products in the absence of transition-metals (Scheme 1b, 1c). During the investigation of these three-component indole-to-carbazole reactions, we observed a special ester group transfer phenomenon when electron-deficient olefins with large substituents such as butyl methacrylate were used as the substrates, which provided different substituted carbazoles. We speculated that a [1s,6s] sigmatropic shift was occurred after the formal [2+2'+2"] annulation. This interesting result prompted us to



further systematic investigate this unusual reaction in order to understand the reaction mechanism and develop a new method for synthesis multiple substituted carbazole derivatives. Herein, we present a novel three-component cascade synthesis of substituted carbazoles via a [1s,6s] sigmatropic shift under metal-free conditions. This method introduces an ester group at the C2 position of the carbazole ring, while the synthesis we reported before provides the carbazoles with an ester group in C1 position. Furthermore, decarboxylative carbazole products also can be generated when some other olefins were used under standard conditions (Scheme 1d).

RESULTS AND DISSCUSSION Based on our previous work, we commenced our investigation by using indole (1a), acetophenone (2a), and butyl methacrylate (3a) as the model substrates (Table 1). To our delight, the desired product 5a was obtained in 61% yield in the presence of KI (0.2 equiv) and p-toluenesulfonic acid (TsOH, 0.2 equiv) (Table 1, entry 1). Various iodide-containing reagents such as elemental iodine, ICl and NaI were tested,16 which all lead to lower reaction yield (entries 2-4). A control experiement showed that a very low yield was obtained in the absence of iodide-containing additive (entry 5). Subsequently, we evaluated several Brφnsted acid additives, however, the reaction yield was not enhanced (entries 6-8). Again, independently using of TsOH as the additive significantly decreased the reaction yield (entry 9). During the optimization process, we observed that an intermediate 4a was existed. We speculated that oxygen as the sole oxidantis was not efficient enough to convert all of the intermediate 4a into the target product. To our delight, the yield of 5a could be


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smoothly improved to 76% when 1.5 equiv. of dimethyl sulfoxide (DMSO) was used as the co-oxidant (entry 10).17 Finally, the yield was further improved to 90% when a small amount of water was added together with the reaction time prolonged to 36 h for the second step (entry 11). Table 1. Screening the Reaction Conditions.a

Entry

Additive 1

Additive 2

Oxidant

Yield (%)b

1

KI

TsOH

O2

61

2

I2

TsOH

O2

39

3

ICl

TsOH

O2

37

4

NaI

TsOH

O2

33

TsOH

O2

12

5 6

KI

TfOH

O2

54

7

KI

TFA

O2

27

8

KI

MSA

O2

50

9

KI

O2

9

10

KI

TsOH

DMSO+O2

76

11c,d

KI

TsOH

DMSO+O2

90 (70) e

12 c,d,f

KI

TsOH

DMSO+O2

73



a

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Reaction conditions: 1a (0.2 mmol), 2a (0.6 mmol, 3.0 equiv), 3a (0.4 mmol, 2.0

equiv), NH4I (0.04 mmol), PhCF3 (0.5 mL, sealed tube), air, 160 oC, 30 h. After cooling to room temperature, additive 1 (0.04 mmol) and additive 2 (0.04 mmol) were added to the reaction mixture and heated to 160 oC for additional 24 h, under O2.

b

Yield were determined by GC analysis using dodecane as the internal standard. c 30 μL H2O added.

d

The second step reaction time prolonged to 36 h. e Isolated yield.

f

150 oC. With the optimized reaction conditions in hand, indole substrates with various substituents were tested and the results were summarized in Table 2. In general, N-alkylindoles proceeded smoothly to give the fused N-heterocycles in moderate to good yields (5a-5b). 1H-Indole also could be used as the substrate to give the carbazole product 5d in 38% yield. Much lower yield was obtained when N-phenylindole was used (5c). Good yields were achieved when methyl substituent was located at C7, C6 and C5 positions (5e, 5f and 5i). However, the product could not be generated when a methyl group was presented at C4 position mainly due to the steric hindrance effect (5o). Meanwhile, various halogen-substituted carbazoles also could be obtained in moderate yields (5g-5h, 5j-5l). It should be noted that N-methylindoles with strong electron-withdrawing group gave much lower yield (5n). Table 2. The Scope of Indoles.a


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a

Reaction conditions: 1a (0.2 mmol), 2a (0.6 mmol, 3.0 equiv), 3a (0.4 mmol, 2.0 equiv), NH4I

(0.04 mmol), PhCF3 (0.5 mL, sealed tube), air, 160 oC, 30 h. Then KI (0.04 mmol), TsOH (0.04 mmol), DMSO (0.3 mmol) and H2O (30 μL) add, under O2, 160 oC, 36 h.

Subsequently, the substrate scope of ketones was explored (Table 3). Good yields were obtained when methyl and phenyl substituents presented at the para position of acetophenones (6a, 6b). Halogen groups in ketone substrates were well tolerated to give the desired products in good yields (6c-6e). The reaction was also suitable for those acetophenones with strong electron-withdrawing substituents (6g-6i). No obvious steric effect was observed when the substituents were located at the meta position (6j-6k). However, much lower reaction yield was observed when the



substituent was located at the ortho position (6l). Bulky 1-(naphthalen-2-yl)ethanone and 1-(phenanthren-3-yl)ethanone also react well, giving the corresponding products in moderate yields (6n, 6o). To our delight, hetero aromatic ketones such as 1-(thiophen-3-yl)ethanone also could provide the carbazole product 6p in 32% yield. Regrettably, aliphatic ketones such as pentan-3-one gave a very low yield (6q). When aliphatic aldehydes were used as the substrate, the corresponding products were not detected. Table 3. The Scope of Ketones.a

a


(0.04 mmol), PhCF3 (0.5 mL, sealed tube), air, 160 oC, 30 h. Then KI (0.04 mmol), TsOH (0.04 mmol), DMSO (0.3 mmol) and H2O (30 μL) add, under O2, 160 oC, 36 h.


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Furthermore, a range of electron-withdrawing alkenes were investigated under the optimized conditions (Table 4). Isobutyl methacrylate, ethyl methacrylate and benzyl methacrylate all could smoothly react to give the corresponding products in moderate to good yields (7a-7c). Interestingly, the carbazole carboxylic acid 7d was obtained in 52% yield when phenyl methacrylate was used. In addition, the product 7e was obtained in 41% yield and it's structure was confirmed by single-crystal X-ray diffraction.18 Unfortunately, the product 7f could not be observed when ethyl 2-phenylacrylate was used as the substrate. Table 4. The Scope of Alkenes.a

a


(0.04 mmol), PhCF3 (0.5 mL, sealed tube), air, 160 oC, 30 h. Then KI (0.04 mmol), TsOH (0.04 mmol), DMSO (0.3 mmol) and H2O (30 μL) add, under O2, 160 oC, 36 h. b Phenyl methacrylate

was used. Unexpectedly, cleavage of C-C bond occurred under metal-free conditions when some other alkenes were used, giving different carbazole products. For example,



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when tert-butyl methacrylate, methacrylic acid, methacrylamide and methacryloyl chloride were used, the decarboxylation occurred to give the same carbazole product 8a

(Scheme

2a).

Unbelievably,

when

dimethyl

2-methylenesuccinate

and

methacrylonitrile were used as the substrates, carbazole derivatives 8b and 8c were obtained in 60% and 30% yields, respectively, through Csp2-Csp3 bond cleavage process (Scheme 2b, 2c). This unusual C-C bond cleavage reaction provides a new way to synthesize carbazole derivatives with different substitution patterns. Scheme 2. C-C Bond Cleavage for the Carbazole Formation.

a

4.0 equiv of methacrylonitrile was used. For a better understanding of the reaction mechanism, several control experiments

were conducted (Scheme 3). The intermediate 4a was obtained as the major product in 72% isolated yield in the first step (Scheme 3a). When N-methyl indole and acetophenone were treated under the standard conditions, the 3-vinylindole B was


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generated in 77% yield (Scheme 3b). And the 3-vinylindole B coupled with butyl methacrylate 3a to give the intermediate 4a in 70% yield (Scheme 3c). The intermediate 4a could be further converted into the final carbazole products 5a in 75% yield (Scheme 3d). Additionally, several free radical capture experiments were carried out (Scheme 3e). While the addition of butylated hydroxytoluene (BHT) or ethene-1,1-diyldibenzene in the second step did not affect the efficiency of the desired transformation, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) completely prevented the product 5a from forming and afforded the decarboxylative adduct 8a in 20% GC yield. The radical capture experiments showed that the process of ester migration may be achieved through a free radical pathway. Scheme 3. Control Experiments



On the basis of above results and some related literatures,16,19 a possible reaction pathway for this reaction was illustrated in Scheme 4. Initially, the 3-vinylindole B is generated undergoes nucleophilic addition of indole to the carbonyl followed by the elimination of H2O. Then a Michael-type addition is followed by nucleophilic annulation to give the intermediate 4a. Nitrogen-centered radical D is formed via single-electron oxidation process from 4a in the presence of iodide-containing additive. Tautomerization of D provides intermediate E. Subsequent single-electron oxidation and deprotonation or hydrogen atom transfer of E yields an intermediate F, which can be further converted into dihydrocarbazole G via a deprotonation. Meanwhile, the second single-electron oxidative dehydrogenation or hydrogen atom transfer of G affords an intermediate J. A [1s,6s] sigmatropic shift appears to result in the intermediate K, which can be further converted into the intermediate L, followed by a deprotonation to generate the final product 5a. Scheme 4. Possible Reaction Pathway


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To support the proposed reaction pathway in Scheme 4, we carried out DFT (Density Function Theory) calculations. The ground and transition states of the complexes were calculated using DFT method at the B3LYP/6-31G* level (The details of the computational methods in the Experimental/Methods section). All stationary points were characterized by frequency calculations to confirm their identity as either local minima or first-order saddle points (see Supporting Information). All free energies (Table S1) at the optimized structures were calculated by using the same level of theory at 298.15 K. For comparision, the relative energies for all the compounds and the transition states were also computed using the 6-311G* basis set for all atoms. Since the Density functional theory (DFT) calculation of the dehydroaromatization of tetrahydrocarbazole has been reported before.17d Here we employed the DFT method to explore the process of migration. The intermediate J1 could be further converted into the intermediate L1 via the transition state TS1, or the intermediate L2 via the transition state TS2. As shown in Scheme 5, the energy barrier for the step of J1 to TS1 was predicted to be 23.1 kcal mol−1 at the B3LYP/6-31G* level (or 22.1 kcal mol−1 at the B3LYP/6-311G* level), while the barrier (J1 to TS2) was predicted to be 33.9 kcal mol−1 at the B3LYP/6-31G* level (or 25.9 kcal mol−1 at the B3LYP/6-311G* level). The energy barrier of forming the transition state TS1 is lower than the transition state TS2, suggesting that forming the transition state TS1 is more competitive. These are consistent with the experimental observation that only products arising from ester group shift are observed.



Scheme 5. DFT Calculations of the Shift Step. Free energies are calculated at the B3LYP/6-31G* level. And the free energies in brackets are calculated at the B3LYP/6-311G* level. Ar = biphenyl.

CONCLUSION In summary, we have developed a novel method for the synthesis of substituted carbazoles from indoles, aromatic ketones and electron deficient alkenes under metal-free conditions. The cascade involving condensation, cyclization and dehydrogenative aromatization with a [1s,6s] sigmatropic shift was realized in one-pot. The present indole-to-carbazole protocol starts from cheap and readily available starting materials, affording diverse carbazole products with good regioselectivity and well functional group tolerance. Furthermore, DFT calculations were carried out to support the proposed reaction pathway. EXPERIMENTAL SECTION


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The details of computational methods: All of the calculations were carried out with the Gaussian 09 program package in the gas phase.20 The ground and transition states of the complexes were calculated using density functional theory (DFT) at the B3LYP level.21,22 The 6-31G* were used for C, H, N, O and S atoms.23 All stationary points were characterized by frequency calculations to confirm their identity as either local minima or first-order saddle points. The results showed that all isomers (J1, L1 and L2) process positive lowest vibrational frequencies, indicating all the geometries correspond to local minima. The transition states of the complexes (TS1 and TS2) have single imaginary frequency. All free energies at the optimized structures were calculated by using the same level of theory at 298.15 K in the gas phase. For comparision, the relative energies for all the compounds and the transition states were also computed using the 6-311G* basis set for all atoms. General information. All reagents were obtained from commercial suppliers and used without further purification. All reactions were carried out under the standard conditions unless otherwise noted. Column chromatography was performed using aluminum oxide (neutral) (100-200 mesh). 1H NMR and

13

C NMR spectra were

recorded on Bruker-AV (400 and 100 MHz, respectively) instrument internally referenced to tetramethylsilane (TMS) or chloroform signals. Mass spectra were measured on Agilent 5975 GC-MS instrument (EI). High-resolution mass spectra were recorded at Keecloud (Shanghai) Biotechnology co. LTD. HRMS were conducted by using electrospraying ionization (ESI) and were performed on a Thermo Scientific LTQ Orbitrap XL. The structures of known compounds were further



corroborated by comparing their 1H NMR, 13C NMR data and MS data with those of literature. All reagents were obtained from commercial suppliers and used without further purification. General procedure for carbazole synthesis. Ammonium iodide (5.8 mg, 0.04 mmol) was added to a 20 mL oven-dried sealed tube. The sealed tube was added 1-methyl-1H-indole (25.0 μL, 0.2 mmol), acetophenone (70.4 μL, 0.6 mmol), butyl methacrylate (63.5 μL, 0.4 mmol), and (trifluoromethyl)benzene (0.5 mL) by syringe. The sealed tube was stirred at 160 oC for 30 h, under air. After cooling to room temperature, KI (6.6 mg, 0.04 mmol), DMSO (21 µL, 0.3 mmol), H2O (30 µL) and p-toluenesulfonic acid (7.6 mg, 0.04 mmol) were added to the sealed tube. The sealed tube was purged with oxygen gas for three times and was stirred at 160 oC for 36 h. After cooling to room temperature, the volatiles were removed under reduced pressure. The residue was purified by column chromatography on aluminum oxide (neutral) (petroleum ether/EtOAc = 200:1) to yield the desired product 5a as light yellow solid (51.9 mg, 70% yield), mp 89-91 oC. Rf = 0.31 (200:1 petroleum ether/EtOAc). Butyl 1,9-dimethyl-4-phenyl-2,3,4,9-tetrahydro-1H-carbazole-1-carboxylate [4a (dr = 9:50)]. Pale yellow liquid (54.0 mg, 72% yield), Rf = 0.29 (300:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3, ppm) δ 7.30-7.15 (m, 7H), 7.08 (d, J = 7.6 Hz, 1H), 6.94 (t, J = 7.4 Hz, 1H), 4.36 (t, J = 4.2 Hz, 1H), 4.27-4.20 (m, 1H), 4.08-4.02 (m, 1H), 3.63 (s, 3H, NCH3), 2.34-2.24 (m, 2H), 1.97-1.92 (m, 1H), 1.74-1.69 (m, 1H), 1.65 (s, 3H, CH3), 1.6.0-1.53 (m, 2H, CH2), 1.33-1.24 (m, 2H, CH2), 0.87 (t, J = 7.4 Hz, 3H, CH3); 13C {1H} NMR (100 MHz, CDCl3, ppm) δ 177.0


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(C=O), 145.4, 138.0, 137.7, 128.4 (2C), 128.0 (2C), 126.2, 125.9, 121.5, 119.1, 118.9, 111.5, 108.6, 65.1 (OCH2), 43.5, 38.2, 33.4, 30.6, 30.5, 29.5, 23.4, 19.0, 13.6 (CH3); HRMS calcd. for. C25H30NO2 [M+H]+ 376.2271, found 376.2268. Butyl 1,9-dimethyl-4-phenyl-9H-carbazole-2-carboxylate (5a). Light yellow solid (51.9 mg, 70% yield), mp 89-91 oC. Rf = 0.31 (200:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3, ppm) δ 7.57-7.49 (m, 6H), 7.45-7.38 (m, 2H), 7.30 (d, J = 8.0 Hz, 1H), 6.95 (t, J = 7.2 Hz, 1H), 4.35 (t, J = 6.8 Hz, 2H, OCH2), 4.17 (s, 3H, NCH3), 3.06 (s, 3H, CH3), 1.80-1.73 (m, 2H, CH2), 1.53-1.43 (m, 2H, CH2)), 0.98 (t, J = 7.4 Hz, 3H, CH3); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 169.1 (C=O), 143.6, 141.0, 140.7, 134.9, 129.3, 129.3 (2C), 128.4 (2C), 127.6, 126.4, 123.5, 122.8, 122.4, 122.0, 121.1, 119.0, 108.9, 64.9 (OCH2), 33.8 (NCH3), 30.8, 19.3, 17.2 (CH3), 13.8 (CH3); HRMS calcd. for. C25H26NO2 [M+H]+ 372.1958, found 372.1960. Butyl 9-benzyl-1-methyl-4-phenyl-9H-carbazole-2-carboxylate (5b). Pale yellow liquid (42.0 mg, 47% yield). Rf = 0.28 (200:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3, ppm) δ 7.61-7.59 (m, 2H), 7.56-7.48 (m, 4H), 7.36-7.23 (m, 6H), 7.12 (d, J = 6.8 Hz, 2H), 6.97 (t, J = 7.6 Hz, 1H), 5.81 (s, 2H, NCH2), 4.32 (t, J = 6.8 Hz, 2H, OCH2), 2.83 (s, 3H, CH3), 1.77-1.70 (m, 2H, CH2), 1.50-1.40 (m, 2H, CH2), 0.95 (t, J = 7.4 Hz, 3H, CH3); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 169.2 (C=O), 143.3, 140.7, 140.5, 138.3, 135.0, 129.7, 129.3 (2C), 128.9 (2C), 128.5 (2C), 127.7, 127.3, 126.7, 125.6 (2C), 123.7, 122.8, 122.6, 122.2, 120.8, 119.5, 109.3, 65.0 (OCH2), 49.3 (NCH2), 30.8, 19.3, 16.4 (CH3), 13.7 (CH3); HRMS calcd. for. C31H30NO2 [M+H]+ 448.2271, found 448.2278.



Butyl 1-methyl-4-phenyl-9H-carbazole-2-carboxylate (5d). Pale yellow solid (21.7 mg, 38% yield), mp 133-135 oC. Rf = 0.30 (20:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3, ppm) δ 8.29 (s, 1H, NH), 7.70 (s, 1H, H3), 7.62 (d, J = 7.2 Hz, 2H), 7.56-7.47 (m, 5H), 7.40 (t, J = 7.6 Hz, 1H), 7.00 (t, J = 7.6 Hz, 1H), 4.36 (t, J = 6.8 Hz, 2H, OCH2), 2.88 (s, 3H, CH3), 1.81-1.74 (m, 2H, CH2), 1.52-1.44 (m, 2H, CH2), 0.98 (t, J = 7.4 Hz, 3H, CH3); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 168.3 (C=O), 140.6, 140.6, 139.6, 134.7, 129.3 (2C), 128.5 (2C), 127.6, 126.6, 126.4, 123.1, 123.0, 122.9, 122.8, 121.3, 119.5, 110.8, 64.8 (OCH2), 30.9, 19.4, 14.7 (CH3), 13.8(CH3); HRMS calcd. for. C24H24NO2 [M+H]+ 358.1802, found 358.1806. Butyl 1,8,9-trimethyl-4-phenyl-9H-carbazole-2-carboxylate (5e). Pale yellow solid (52.4 mg, 68% yield), mp 101-103 oC. Rf = 0.32 (200:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3, ppm) δ 7.58 (s, 1H, H3), 7.54-7.45 (m, 5H), 7.15-7.10 (m, 2H), 6.85 (t, J = 7.6 Hz, 1H), 4.34 (t, J = 6.8 Hz, 2H, OCH2), 4.07 (s, 3H, NCH3), 2.97 (s, 3H, CH3), 2.76 (s, 3H, CH3), 1.80-1.73 (m, 2H, CH2), 1.53-1.43 (m, 2H, CH2), 0.98 (t, J = 7.4 Hz, 3H, CH3); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 168.7 (C=O), 145.7, 145.4, 140.6, 134.5, 129.7, 129.3 (2C), 128.9, 128.4 (2C), 127.5, 125.2, 124.1, 123.8, 122.6, 121.6, 120.7, 120.1, 64.8 (OCH2), 37.8 (NCH3), 30.8, 20.4 (CH3), 19.3, 18.2 (CH3), 13.8 (CH3); HRMS calcd. for. C26H28NO2 [M+H]+ 386.2115, found 386.2116. Butyl 1,7,9-trimethyl-4-phenyl-9H-carbazole-2-carboxylate (5f). Pale yellow solid (49.3 mg, 64% yield), mp 103-105 oC. Rf = 0.30 (300:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3, ppm) δ 7.56-7.44 (m, 6H), 7.19-7.16 (m, 2H), 6.77 (d, J =


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8.0 Hz, 1H), 4.34 (t, J = 6.8 Hz, 2H, OCH2), 4.10 (s, 3H, NCH3), 3.03 (s, 3H, CH3), 2.49 (s, 3H, CH3), 1.80-1.72 (m, 2H, CH2), 1.52-1.43 (m, 2H, CH2), 0.97 (t, J = 7.4 Hz, 3H, CH3); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 169.1 (C=O), 144.0, 141.0, 140.8, 136.8, 134.4, 129.2 (2C), 128.8 (2C), 128.4, 127.5, 123.7, 122.4 (2C), 121.1, 120.6, 119.6, 109.1, 64.9 (OCH2), 33.7 (NCH3), 30.8, 22.2 (CH3), 19.3, 17.1 (CH3), 13.8 (CH3); HRMS calcd. for. C26H28NO2 [M+H]+ 386.2115, found 386.2116. Butyl

7-fluoro-1,9-dimethyl-4-phenyl-9H-carbazole-2-carboxylate

(5g).

Pale

yellow solid (38.9 mg, 50% yield), mp 102-104 oC. Rf = 0.28 (200:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3, ppm) δ 7.53-7.47 (m, 6H), 7.22-7.19 (m, 1H), 7.03 (dd, J = 10.1, 2.2 Hz, 1H), 6.67 (td, J = 9.0, 2.3 Hz, 1H), 4.35 (t, J = 6.6 Hz, 2H, OCH2), 4.11 (s, 3H, NCH3), 3.04 (s, 3H, CH3), 1.80-1.73 (m, 2H, CH2), 1.52-1.43 (m, 2H, CH2), 0.98 (t, J = 7.4 Hz, 3H, CH3); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 169.0 (C=O), 162.4 (d, JCF = 242.0 Hz, C-F), 144.5 (d, JCF = 11.7 Hz), 141.5 (d, JCF = 2.0 Hz), 140.4, 134.4, 129.2 (2C), 129.1, 128.5 (2C), 127.7, 123.9 (d, JC-F = 10.2 Hz), 123.3, 122.9, 121.2, 118.3, 107.3 (d, JCF = 23.6 Hz), 95.7 (d, JCF = 26.5 Hz), 65.0 (OCH2), 34.0 (NCH3), 30.8, 19.3, 17.1 (CH3), 13.7 (CH3); HRMS calcd. for. C25H25FNO2 [M+H]+ 390.1864, found 390.1864. Butyl

7-chloro-1,9-dimethyl-4-phenyl-9H-carbazole-2-carboxylate

(5h).

Pale

yellow solid (51.0 mg, 63% yield), mp 105-107 oC. Rf = 0.29 (200:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3, ppm) δ 7.59-7.49 (m, 6H), 7.37 (s, 1H), 7.18 (d, J = 8.4 Hz, 1H), 6.91 (d, J = 8.4 Hz, 1H), 4.35 (t, J = 6.8 Hz, 2H, OCH2), 4.14 (s, 3H, NCH3), 3.04 (s, 3H, CH3), 1.80-1.73 (m, 2H, CH2), 1.52-1.43 (m, 2H,



Page 20 of 44

CH2), 0.98 (t, J = 7.4 Hz, 3H, CH3); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 169.0 (C=O), 144.1, 141.3, 140.3, 134.8, 132.4, 129.8, 129.1 (2C), 128.6 (2C), 127.8, 123.6, 123.1, 122.9, 121.3, 120.5, 119.6, 109.1, 65.0 (OCH2), 33.9 (NCH3), 30.8, 19.3, 17.1 (CH3), 13.8 (CH3); HRMS calcd. for. C25H25ClNO2 [M+H]+ 406.1568, found 406.1568. Butyl 1,6,9-trimethyl-4-phenyl-9H-carbazole-2-carboxylate (5i). Pale yellow solid (53.9 mg, 70% yield), mp 85-87 oC. Rf = 0.28 (300:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3, ppm) δ 7.57-7.47 (m, 6H), 7.28-7.23 (m, 2H), 7.08 (s, 1H), 4.34 (t, J = 6.8 Hz, 2H, OCH2), 4.12 (s, 3H, NCH3), 3.04 (s, 3H, CH3), 2.27 (s, 3H, CH3), 1.80-1.73 (m, 2H, CH2), 1.52-1.43 (m, 2H, CH2), 0.97 (t, J = 7.4 Hz, 3H, CH3); 13

C{1H} NMR (100 MHz, CDCl3, ppm) δ 169.2 (C=O), 142.0, 141.3, 140.8, 134.8,

129.3 (2C), 129.1, 128.3 (2C), 128.2, 127.8, 127.6, 123.4, 122.7, 122.2, 122.0, 121.1, 108.7, 64.9 (OCH2), 33.8 (NCH3), 30.8, 21.3, 19.3, 17.2 (CH3), 13.8 (CH3); HRMS calcd. for. C26H28NO2 [M+H]+ 386.2114, found 386.2116. Butyl

6-fluoro-1,9-dimethyl-4-phenyl-9H-carbazole-2-carboxylate

(5j).

Pale

yellow solid (44.3 mg, 57% yield), mp 105-107 oC. Rf = 0.29 (200:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3, ppm) δ 7.53-7.49 (m, 5H), 7.47 (s, 1H), 7.31-7.28 (m, 1H), 7.16 (td, J = 8.8, 2.6 Hz, 1H), 6.94 (dd, J = 9.8, 2.4 Hz, 1H), 4.35 (t, J = 6.8 Hz, 2H, OCH2), 4.15 (s, 3H, NCH3), 3.04 (s, 3H, CH3), 1.80-1.73 (m, 2H, CH2), 1.52-1.43 (m, 2H, CH2), 0.98 (t, J = 7.4 Hz, 3H, CH3);

13

C{1H} NMR (100

MHz, CDCl3, ppm) δ 169.0 (C=O), 156.7 (d, JCF = 233.6 Hz, C-F ), 141.8, 140.0 (d, J JCF = 13.8 Hz), 135.1, 129.9, 129.1 (2C), 128.6 (2C), 127.9, 123.0 (d, JCF = 4.3 Hz),


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122.3, 122.2, 122.2, 121.3, 114.3 (d, JCF = 25.6 Hz), 109.5 (d, JCF = 9.1 Hz), 108.4 (d, JCF = 24.8 Hz), 65.0 (OCH2), 34.0 (NCH3), 30.8, 19.3, 17.1 (CH3), 13.8 (CH3); HRMS calcd. for. C25H25FNO2 [M+H]+ 390.1864, found 390.1865. Butyl 6-bromo-1,9-dimethyl-4-phenyl-9H-carbazole-2-carboxylate (5k). Pale yellow solid (40.5 mg, 50% yield), mp 96-98 oC. Rf = 0.27 (300:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3) δ 7.57-7.50 (m, 5H), 7.48 (s, 1H), 7.38-7.35 (m 1H), 7.30-7.27 (m, 1H), 7.25-7.24 (m, 1H), 4.35 (t, J = 6.8 Hz, 2H, OCH2), 4.14 (s, 3H, NCH3), 3.03 (s, 3H, CH3), 1.80-1.73 (m, 2H, CH2), 1.52-1.43 (m, 2H, CH2), 0.98 (t, J = 7.4 Hz, 3H, CH3); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 169.0 (C=O), 141.8, 141.4, 140.0, 135.1, 130.1, 129.1 (2C), 128.6 (2C), 128.0, 126.5, 124.4, 123.0, 122.6, 122.6, 122.2, 121.3, 109.9, 65.1 (OCH2), 33.9 (NCH3), 30.8, 19.3, 17.1 (CH3), 13.8 (CH3); HRMS calcd. for. C25H25ClNO2 [M+H]+ 406.1568, found 406.1562. Butyl

6-bromo-1,9-dimethyl-4-phenyl-9H-carbazole-2-carboxylate

(5l).

Pale

yellow solid (38.6 mg, 43% yield), mp 93-95 oC. Rf = 0.28 (300:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3) δ 7.56-7.50 (m, 5H), 7.48 (s, 1H), 7.38-7.36 (m, 1H), 7.30 (d, J = 8.8 Hz, 1H), 7.25-7.24 (m, 1H), 4.35 (t, J = 6.6 Hz, 2H, OCH2), 4.15 (s, 3H, NCH3), 3.04 (s, 3H, CH3), 1.80-1.73 (m, 2H, CH2), 1.53-1.43 (m, 2H, CH2), 0.98 (t, J = 7.4 Hz, 3H, CH3) ; 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 169.0 (C=O), 141.8, 141.4, 140.0, 135.1, 130.1, 129.1 (2C), 128.6 (2C), 128.0, 126.5, 124.4, 123.0, 122.6, 122.6, 122.2, 121.3, 109.9, 65.1 (OCH2), 33.9 (NCH3), 30.8, 19.3,



Page 22 of 44

17.1 (CH3), 13.8 (CH3); HRMS calcd. for. C25H25BrNO2 [M+H]+ 450.1063, found 450.1062. Butyl 6-methoxy-1,9-dimethyl-4-phenyl-9H-carbazole-2-carboxylate (5m). Pale yellow solid (48.1 mg, 60% yield), mp 76-78 oC. Rf = 0.33 (50:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3, ppm) δ 7.56-7.45 (m, 6H), 7.28-7.24 (m, 1H), 7.07-7.04 (m, 1H), 6.71 (s, 1H), 4.35 (t, J = 6.8 Hz, 2H, OCH2), 4.12 (s, 3H, NCH3), 3.55 (s, 3H, OCH3), 3.03 (s, 3H, CH3), 1.80-1.73 (m, 2H, CH2), 1.53-1.43 (m, 2H, CH2), 0.98 (t, J = 7.4 Hz, 3H, CH3);

13

C{1H} NMR (100 MHz, CDCl3, ppm) δ

169.2 (C=O), 153.1, 141.5, 140.5, 138.7, 134.8, 129.4 (2C), 129.1, 128.3 (2C), 127.6, 123.3, 122.1, 121.8, 121.4, 116.0, 109.7, 105.1, 64.9 (OCH2), 55.4 (OCH3), 33.9 (NCH3), 30.8, 19.3, 17.1 (CH3), 13.8 (CH3); HRMS calcd. for. C26H28NO3 [M+H]+ 402.2064, found 402.2067. Butyl

6-cyano-1,9-dimethyl-4-phenyl-9H-carbazole-2-carboxylate

(5n).

Pale

yellow solid (20.6 mg, 26% yield), mp 134-136 oC. Rf = 0.31 (20:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3, ppm) δ 7.66 (d, J = 8.4, 1H), 7.59-7.49 (m, 7H), 7.44 (d, J = 8.4 Hz, 1H), 4.36 (t, J = 6.6 Hz, 2H, OCH2), 4.22 (s, 3H, NCH3), 3.06 (s, 3H, CH3), 1.81-1.74 (m, 2H, CH2), 1.53-1.43 (m, 2H, CH2), 0.98 (t, J = 7.4 Hz, 3H, CH3); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 168.7 (C=O), 144.8, 141.4, 139.6, 135.4, 131.0, 129.4, 128.9 (2C), 128.8 (2C), 128.4, 127.6, 123.5, 122.6, 122.1, 121.4, 120.3, 109.6, 101.9, 65.2 (OCH2), 34.0 (NCH3), 30.8, 19.3, 17.0 (CH3), 13.7 (CH3); HRMS calcd. for. C26H25N2O2 [M+H]+ 397.1911, found 397.1913.


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Butyl 1,9-dimethyl-4-(p-tolyl)-9H-carbazole-2-carboxylate (6a). Pale yellow solid (52.4 mg, 68% yield), mp 118-120 oC. Rf = 0.29 (200:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3, ppm) δ 7.48-7.41 (m, 4H), 7.37 (d, J = 8.8 Hz, 2H), 7.33-7.31 (d, J = 7.8 Hz, 2H), 6.96 (t, J = 7.4 Hz, 1H), 4.34 (t, J = 6.8 Hz, 2H, OCH2), 4.16 (s, 3H, NCH3), 3.05 (s, 3H, CH3), 2.49 (s, 3H, PhCH3), 1.80-1.72 (m, 2H, CH2), 1.52-1.43 (m, 2H, CH2), 0.97 (t, J = 7.4 Hz, 3H, CH3)；13C{1H} NMR (100 MHz, CDCl3, ppm) δ 169.2 (C=O), 143.6, 141.1, 137.7, 137.3, 134.9, 129.3, 129.1 (2C), 129.1 (2C), 126.4, 123.6, 122.9, 122.6, 122.1, 121.0, 119.0, 108.9, 64.9 (OCH2), 33.8 (NCH3), 30.8, 21.3 (PhCH3), 19.3, 17.2 (CH3), 13.8 (CH3); HRMS calcd. for. C26H28NO2 [M+H]+ 386.2115, found 386.2118. Butyl 4-([1,1'-biphenyl]-4-yl)-1,9-dimethyl-9H-carbazole-2-carboxylate (6b). Pale yellow solid (64.4 mg, 72% yield), mp 134-136 oC. Rf = 0.31 (100:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3, ppm) δ 7.78-7.73 (m, 4H), 7.64 (d, J = 8.4 Hz, 2H), 7.54 (s, 1H), 7.52-7.37 (m, 6H), 6.98 (t, J = 8.0 Hz, 1H), 4.36 (t, J = 6.8 Hz, 2H, OCH2), 4.18 (s, 3H, NCH3), 3.07 (s, 3H, CH3), 1.81-1.74 (m, 2H, CH2), 1.53-1.44 (m, 2H, CH2), 0.98 (t, J = 7.4 Hz, 3H, CH3); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 169.1 (C=O), 143.6, 141.1, 140.8, 140.4, 139.7, 134.4, 129.7 (2C), 129.4, 128.8 (2C), 127.4, 127.1 (2C), 127.1 (2C), 126.5, 123.5, 122.9, 122.5, 121.9, 121.3, 119.1, 109.0, 65.0 (OCH2), 33.8 (NCH3), 30.8, 19.3, 17.2 (CH3), 13.8 (CH3); HRMS calcd. for. C31H30NO2 [M+H]+ 448.2271, found 448.2271. Butyl 4-(4-fluorophenyl)-1,9-dimethyl-9H-carbazole-2-carboxylate (6c). Pale yellow solid (52.1 mg, 67% yield), mp 88-90 oC. Rf = 0.30 (200:1 petroleum



Page 24 of 44

ether/EtOAc). 1H NMR (400 MHz, CDCl3, ppm) δ 7.53-7.49 (m, 2H), 7.46-7.38 (m, 3H), 7.28 (d, J = 8.0 Hz, 1H), 7.23-7.18 (m, 2H), 6.98 (t, J = 7.4 Hz, 1H), 4.35 (t, J = 6.8 Hz, 2H, OCH2), 4.16 (s, 3H, NCH3), 3.05 (s, 3H, CH3), 1.81-1.74 (m, 2H, CH2), 1.53-1.44 (m, 2H, CH2), 0.98 (t, J = 7.4 Hz, 3H, CH3);

13

C{1H} NMR (100 MHz,

CDCl3, ppm) δ 169.1 (C=O), 162.5 (d, JCF = 244.7 Hz, C-F), 143.5, 141.0, 136.6 (d, JCF = 3.3 Hz), 133.7, 130.9 (d, JCF = 7.9 Hz, 2C), 129.4, 126.5, 123.5, 122.6, 122.5, 121.8, 121.3, 119.1, 115.4 (d, JCF = 21.2 Hz, 2C), 109.0, 65.0 (OCH2), 33.8 (NCH3), 30.8, 19.3, 17.2 (CH3), 13.8 (CH3); HRMS calcd. for. C25H25FNO2 [M+H]+ 390.1864, found 390.1867. Butyl 4-(4-chlorophenyl)-1,9-dimethyl-9H-carbazole-2-carboxylate (6d). Pale yellow liquid (55.1 mg, 68% yield). Rf = 0.29 (200:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3, ppm) δ 7.50- 7.40 (m, 7H), 7.33 (d, J = 8.0 Hz, 1H), 7.00 (t, J = 7.4 Hz, 1H), 4.35 (t, J = 6.6 Hz, 2H, OCH2), 4.18 (s, 3H, NCH3), 3.06 (s, 3H, CH3), 1.81-1.74 (m, 2H, CH2), 1.53-1.44 (m, 2H, CH2), 0.98 (t, J = 7.4 Hz, 3H, CH3); 13


133.5, 130.7 (2C), 129.4, 128.7 (2C), 126.6, 123.3, 122.6, 122.4, 121.7, 121.5, 119.2, 109.1, 65.0 (OCH2), 33.8 (NCH3), 30.8, 19.3, 17.2 (CH3), 13.8 (CH3); HRMS calcd. for. C25H25ClNO2 [M+H]+ 406.1568, found 406.1563. Butyl 4-(4-bromophenyl)-1,9-dimethyl-9H-carbazole-2-carboxylate (6e). Pale yellow solid (65.5 mg, 73% yield), mp 87-89 oC. Rf = 0.28 (200:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3, ppm) δ 7.64 (d, J = 8.4 Hz, 2H), 7.47-7.38 (m, 5H), 7.34 (d, J = 8.0 Hz, 1H), 6.99 (t, J = 7.4 Hz, 1H), 4.35 (t, J = 6.6 Hz, 2H,


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OCH2), 4.16 (s, 3H, NCH3), 3.05 (s, 3H, CH3), 1.81-1.73 (m, 2H, CH2), 1.53-1.43 (m, 2H, CH2), 0.98 (t, J = 7.4 Hz, 3H, CH3);

13

C{1H} NMR (100 MHz, CDCl3, ppm) δ

169.0 (C=O), 143.5, 141.1, 139.6, 133.4, 131.6 (2C), 131.0 (2C), 129.4, 126.6, 123.2, 122.6, 122.3, 121.8, 121.7, 121.6, 119.2, 109.1, 65.0 (OCH2), 33.8 (NCH3), 30.8, 19.3, 17.2 (CH3), 13.8 (CH3); HRMS calcd. for. C25H25BrNO2 [M+H]+ 450.1063, found 450.1066. Butyl 4-(4-methoxyphenyl)-1,9-dimethyl-9H-carbazole-2-carboxylate (6f). White solid (41.1 mg, 51% yield), mp 119-121 oC. Rf = 0.27 (200:1 petroleum ether/EtOAc). 1

H NMR (400 MHz, CDCl3, ppm) δ 7.48-7.36 (m, 6H), 7.32 (d, J = 7.6 Hz, 2H), 6.96

(t, J = 7.6 Hz, 1H), 4.34 (t, J = 6.6 Hz, 2H, OCH2), 4.15 (s, 3H, NCH3), 3.04 (s, 3H, CH3), 2.49 (s, 3H, OCH3), 1.80-1.72 (m, 2H, CH2), 1.52-1.45 (m, 2H, CH2), 0.97 (t, J = 7.4 Hz, 3H, CH3);

13

C{1H} NMR (100 MHz, CDCl3, ppm) δ 169.2 (C=O), 143.5,

141.1, 137.7, 137.3, 134.9, 129.3, 129.1 (2C), 129.1 (2C), 126.4, 123.6, 122.8, 122.5, 122.1, 121.0, 119.0, 108.9, 64.9 (OCH2), 33.8 (NCH3), 30.8, 21.3 (OCH3), 19.3, 17.2 (CH3), 13.8 (CH3); HRMS calcd. for. C26H28NO3 [M+H]+ 402.2064, found 402.2061. Butyl

1,9-dimethyl-4-(4-(methylsulfonyl)phenyl)-9H-carbazole-2-carboxylate

(6g). White solid (54.8 mg, 61% yield), mp 151-153 oC. Rf = 0.32 (20:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3, ppm) δ 8.10 (d, J = 8.4 Hz, 2H), 7.79 (d, J = 8.4 Hz, 2H), 7.49-7.42 (m, 3H), 7.27 (d, J = 8.0 Hz, 1H), 7.00 (t, J = 7.4 Hz, 1H), 4.36 (t, J = 6.8 Hz, 2H, OCH2), 4.19 (s, 3H, NCH3), 3.19 (s, 3H, SO2CH3), 3.07 (s, 3H, CH3), 1.82-1.74 (m, 2H, CH2), 1.53-1.44 (m, 2H, CH2), 0.99 (t, J = 7.4 Hz, 3H, CH3); 13




Page 26 of 44

132.5, 130.3 (2C), 129.5, 127.6 (2C), 127.5, 126.9, 122.9, 122.4, 122.4, 121.3, 119.4, 109.3, 65.1 (OCH2), 44.6 (SO2CH3), 33.8 (NCH3), 30.8, 19.3, 17.3 (CH3), 13.8 (CH3); HRMS calcd. for. C26H28NO4S [M+H]+ 450.1734, found 450.1738. Butyl 4-(4-cyanophenyl)-1,9-dimethyl-9H-carbazole-2-carboxylate (6h). White solid (41.2 mg, 52% yield), mp 125-127 oC. Rf = 0.30 (20:1 petroleum ether/EtOAc). 1

H NMR (400 MHz, CDCl3, ppm) δ 7.81 (d, J = 8.4 Hz, 2H), 7.68 (d, J = 8.4 Hz, 2H),

7.49-7.41 (m, 3H), 7.24 (d, J = 8.4 Hz, 1H), 7.00 (t, J = 7.4 Hz, 1H), 4.36 (t, J = 6.8 Hz, 2H, OCH2), 4.18 (s, 3H, NCH3), 3.07 (s, 3H, CH3), 1.81-1.74 (m, 2H, CH2), 1.53-1.44 (m, 2H, CH2), 0.98 (t, J = 7.4 Hz, 3H, CH3);

13

C{1H} NMR (100 MHz,

CDCl3, ppm) δ 168.8 (C=O), 145.6, 143.6, 141.1, 132.7, 132.3 (2C), 130.1 (2C), 129.5, 126.9, 122.8, 122.3, 122.3, 122.2, 121.3, 119.3, 118.9, 111.5, 109.3, 65.1 (OCH2), 33.8 (NCH3), 30.8, 19.3, 17.3 (CH3), 13.7 (CH3); HRMS calcd. for. C26H25N2O2 [M+H]+ 397.1916, found 397.1918. Butyl 1,9-dimethyl-4-(4-nitrophenyl)-9H-carbazole-2-carboxylate (6i). Yellow solid (37.5 mg, 45% yield), mp 141-143oC. Rf = 0.26 (20:1 petroleum ether/EtOAc). 1

H NMR (400 MHz, CDCl3, ppm) δ 8.38 (d, J = 8.8 Hz, 2H), 7.74 (d, J = 8.8 Hz, 2H),

7.49-7.42 (m, 3H), 7.27 (d, J = 8.0 Hz, 1H), 7.00 (t, J = 8.0 Hz, 1H), 4.37 (t, J = 6.8 Hz, 2H, OCH2), 4.19 (s, 3H, NCH3), 3.07 (s, 3H, CH3), 1.82-1.75 (m, 2H, CH2), 1.53-1.44 (m, 2H, CH2), 0.99 (t, J = 7.4 Hz, 3H, CH3); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 168.8 (C=O), 147.6, 147.4, 143.6, 141.1, 132.2, 130.3 (2C), 129.5, 126.9, 123.8 (2C), 122.8, 122.6, 122.3, 122.2, 121.2, 119.4, 109.3, 65.2 (OCH2), 33.8


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(NCH3), 30.8, 19.3, 17.3 (CH3), 13.8 (CH3); HRMS calcd. for. C25H25N2O4 [M+H]+ 417.1809, found 417.1812. Butyl 4-(3-chlorophenyl)-1,9-dimethyl-9H-carbazole-2-carboxylate (6j). Light yellow solid (55.1 mg, 68% yield), mp 103-105 oC. Rf = 0.28 (300:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3, ppm) δ 7.56 (s, 1H), 7.47-7.38 (m, 6H), 7.32 (d, J = 8.0 Hz, 1H), 6.99 (t, J = 7.4 Hz, 1H), 4.35 (t, J = 6.8 Hz, 2H, OCH2), 4.16 (s, 3H, NCH3), 3.05 (s, 3H, CH3), 1.81-1.74 (m, 2H, CH2), 1.53-1.44 (m, 2H, CH2), 0.98 (t, J = 7.4 Hz, 3H, CH3); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 169.0 (C=O), 143.5, 142.5, 141.0, 134.3, 133.2, 129.7, 129.4, 129.3, 127.7, 127.6, 126.6, 123.2, 122.6, 122.3, 121.7, 121.6, 119.3, 109.1, 65.0 (OCH2), 33.8 (NCH3), 30.8, 19.3, 17.2 (CH3), 13.8 (CH3); HRMS calcd. for. C25H25ClNO2 [M+H]+ 406.1568, found 406.1566. Butyl 4-(3-bromophenyl)-1,9-dimethyl-9H-carbazole-2-carboxylate (6k). Light yellow solid (63.7 mg, 71% yield), mp 102-104 oC. Rf = 0.29 (300:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3, ppm) δ 7.72 (s, 1H), 7.62 (d, J = 7.2 Hz, 1H), 7.50-7.36 (m, 5H), 7.32 (d, J = 8.0 Hz, 1H), 7.00 (t, J = 7.2 Hz, 1H), 4.36 (t, J = 6.6 Hz, 2H, OCH2), 4.17 (s, 3H, NCH3), 3.05 (s, 3H, CH3), 1.81-1.74 (m, 2H, CH2), 1.53-1.44 (m, 2H, CH2), 0.98 (t, J = 7.4 Hz, 3H, CH3); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 169.0 (C=O), 143.6, 142.8, 141.0, 133.1, 132.2, 130.7, 130.0, 129.4, 128.0, 126.6, 123.2, 122.6, 122.5, 122.3, 121.7, 121.6, 119.3, 109.1, 65.0 (OCH2), 33.8 (NCH3), 30.8, 19.3, 17.2 (CH3), 13.8 (CH3); HRMS calcd. for. C25H25BrNO2 [M+H]+ 450.1063, found 450.1063.



Butyl

4-(3,4-dichlorophenyl)-1,9-dimethyl-9H-carbazole-2-carboxylate

Page 28 of 44

(6m).

Light yellow solid (47.4 mg, 54% yield), mp 144-146 oC. Rf = 0.28 (200:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3, ppm) δ 7.67 (s, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.46-7.39 (m, 4H), 7.35 (d, J = 8.0 Hz, 1H), 7.02 (t, J = 8.0 Hz, 1H), 4.36 (t, J = 6.8 Hz, 2H, OCH2), 4.17 (s, 3H, NCH3), 3.05 (s, 3H, CH3), 1.82-1.74 (m, 2H, CH2), 1.53-1.44 (m, 2H, CH2), 0.99 (t, J = 7.2 Hz, 3H, CH3); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 168.9 (C=O), 143.6, 141.1, 140.7, 132.6, 132.1, 131.8, 131.2, 130.4, 129.5, 128.8, 126.8, 123.1, 122.4, 122.3, 122.0, 121.4, 119.4, 109.2, 65.1 (OCH2), 33.8 (NCH3), 30.8, 19.3, 17.2 (CH3), 13.8 (CH3); HRMS calcd. for. C25H24Cl2NO2 [M+H]+ 440.1179, found 440.1170. Butyl 1,9-dimethyl-4-(naphthalen-2-yl)-9H-carbazole-2-carboxylate (6n). Light yellow liquid (40.4 mg, 48% yield). Rf = 0.29 (200:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3, ppm) δ 8.04 (s, 1H), 7.98 (t, J = 8.4 Hz, 2H), 7.92-7.89 (m, 1H), 7.70 (d, J = 8.4 Hz, 1H), 7.58-7.54 (m, 3H), 7.44-7.39 (m, 2H), 7.30 (d, J = 8.0 Hz, 1H), 6.90-6.87 (m, 1H), 4.36 (t, J = 6.6 Hz, 2H, OCH2), 4.19 (s, 3H, NCH3), 3.09 (s, 3H, CH3), 1.80-1.73 (m, 2H, CH2), 1.50-1.45 (m, 2H, CH2), 0.97 (t, J = 7.4 Hz, 3H, CH3); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 169.2 (C=O), 143.6, 141.2, 138.2, 134.7, 133.5, 132.8, 129.5, 128.2, 127.9, 127.8, 127.8 (2C), 126.5, 126.3, 126.1, 123.6, 122.9, 122.8, 122.0, 121.3, 119.1, 108.9, 65.0 (OCH2), 33.8 (NCH3), 30.8, 19.3, 17.2 (CH3), 13.8 (CH3); HRMS calcd. for. C29H28NO2 [M+H]+ 422.2115, found 422.2111. Butyl 1,9-dimethyl-4-(phenanthren-3-yl)-9H-carbazole-2-carboxylate (6o). Light yellow solid (32.0 mg, 34% yield), mp 67-69 oC. Rf = 0.28 (200:1 petroleum


Page 29 of 44 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


ether/EtOAc). 1H NMR (400 MHz, CDCl3) δ 8.90 (s, 1H), 8.65-8.63 (m, 1H), 8.04 (d, J = 8.0 Hz, 1H), 7.95-7.92 (m, 1H), 7.88-7.80 (m, 3H), 7.64 (s, 1H), 7.62-7.59 (m, 2H), 7.41 (d, J = 4.0 Hz, 2H), 7.32 (d, J = 8.0 Hz, 1H), 6.87-6.83 (m, 1H), 4.37 (t, J = 6.6 Hz, 2H, OCH2), 4.21 (s, 3H, NCH3), 3.11 (s, 3H, CH3), 1.81-1.74 (m, 2H, CH2), 1.53-1.43 (m, 2H, CH2), 0.97 (t, J = 7.4 Hz, 3H, CH3); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 169.2 (C=O), 143.6, 141.2, 138.9, 135.0, 132.3, 131.4, 130.4, 129.5, 128.6, 128.6, 128.1, 127.2, 126.7 (2C), 126.7, 126.5, 123.7, 123.2, 122.9, 122.8, 122.8, 122.0, 121.4, 119.2, 109.0, 65.0 (OCH2), 33.9 (NCH3), 30.8, 19.3, 17.3 (CH3), 13.8 (CH3); HRMS calcd. for. C33H30NO2 [M+H]+ 472.2271, found 472.2277. Butyl

1,9-dimethyl-4-(thiophen-3-yl)-9H-carbazole-2-carboxylate (6p).

Light

yellow solid (24.1 mg, 32% yield), mp 159-161 oC. Rf = 0.30 (200:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3) δ 7.53 (s, 1H), 7.50-7.38 (m, 5H), 7.30 (d, J = 4.8 Hz, 1H), 7.02 (t, J = 7.4 Hz, 1H), 4.35 (t, J = 6.8 Hz, 2H, OCH2), 4.17 (s, 3H, NCH3), 3.05 (s, 3H, CH3), 1.81-1.74 (m, 2H, CH2), 1.54-1.46 (m, 2H, CH2), 0.99 (t, J = 7.4 Hz, 3H, CH3); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 169.1 (C=O), 143.5, 141.0, 141.0, 129.5, 129.3, 129.1, 126.5, 125.5, 124.0, 123.1, 122.7, 122.6, 122.0, 121.0, 119.2, 108.9, 65.0 (OCH2), 33.8 (NCH3), 30.8, 19.3, 17.2 (CH3), 13.8 (CH3); HRMS calcd. for. C23H24NO2S [M+H]+ 378.1522, found 378.1521. Isobutyl 1,9-dimethyl-4-phenyl-9H-carbazole-2-carboxylate (7a). Light yellow solid (50.5 mg, 68% yield), mp 96-98 oC. Rf = 0.28 (200:1 petroleum ether/EtOAc). 1

H NMR (400 MHz, CDCl3, ppm) δ 7.57-7.48 (m, 6H), 7.44-7.36 (m, 2H), 7.31 (d, J

= 7.6 Hz, 1H), 6.95 (t, J = 7.4 Hz, 1H), 4.15 (s, 3H, NCH3), 4.14 (d, J = 6.8 Hz, 2H,



Page 30 of 44

OCH2), 3.06 (s, 3H, CH3), 2.15-2.05 (m, 1H, CH), 1.04 (s, 3H, CH3), 1.02 (s, 3H, CH3);

13

C{1H} NMR (100 MHz, CDCl3, ppm) δ 169.1 (C=O), 143.6, 141.0, 140.7,

134.9, 129.4, 129.2 (2C), 128.5 (2C), 127.6, 126.4, 123.5, 122.8, 122.4, 122.0, 121.2, 119.0, 108.9, 71.2 (OCH2), 33.8 (NCH3), 27.9, 19.3 (2C), 17.2 (CH3); HRMS calcd. for. C25H26NO2 [M+H]+ 372.1958, found 372.1954. Ethyl 1,9-dimethyl-4-phenyl-9H-carbazole-2-carboxylate (7b)12c. Light yellow solid (30.9 mg, 45% yield), mp 103-105 oC. Rf = 0.29 (200:1 petroleum ether/EtOAc). 1

H NMR (400 MHz, CDCl3) δ 7.57-7.46 (m, 6H), 7.45-7.37 (m, 2H), 7.31 (d, J = 8.0

Hz, 1H), 6.95 (t, J = 7.4 Hz, 1H), 4.40 (q, J = 7.2 Hz, 2H, OCH2), 4.16 (s, 3H, NCH3), 3.06 (s, 3H, CH3), 1.41 (t, J = 7.0 Hz, 3H, OCH2CH3);

13

C{1H} NMR (100 MHz,

CDCl3, ppm) δ 169.0 (C=O), 143.6, 141.0, 140.7, 134.9, 129.3 (2C), 128.4 (2C), 127.6, 126.4, 123.6, 122.8, 122.5, 122.0, 121.2, 119.1, 109.0, 61.0 (OCH2), 33.8 (NCH3), 17.1 (CH3), 14.4 (OCH2CH3); HRMS calcd. for. C23H22NO2 [M+H]+ 344.1645, found 344.1649. Benzyl 1,9-dimethyl-4-phenyl-9H-carbazole-2-carboxylate (7c). White solid (48.6 mg, 60% yield), mp 166-168 oC. Rf = 0.28 (200:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3) δ 7.55-7.45 (m, 8H), 7.43-7.31 (m, 5H), 7.29 (d, J = 8.0 Hz, 1H), 6.95 (t, J = 6.8 Hz, 1H), 5.39 (s, 2H, OCH2Ph), 4.16 (s, 3H, NCH3), 3.06 (s, 3H, CH3); 13


134.9, 129.3 (2C), 128.7, 128.6 (2C), 128.5 (2C), 128.3 (2C), 128.2, 127.6, 126.5, 123.8, 122.8, 122.6, 121.9, 121.6, 119.1, 108.9, 66.8 (OCH2Ph), 33.8 (NCH3), 17.2 (CH3); HRMS calcd. for. C28H24NO2 [M+H]+ 406.1802, found 406.1803.


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1,9-Dimethyl-4-phenyl-9H-carbazole-2-carboxylic acid (7d). White solid (32.8 mg, 52% yield), mp 235-237 oC. Rf = 0.24 (2:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3) δ 7.73 (s, 1H, H3), 7.58-7.40 (m, 7H), 7.35 (d, J = 8.0 Hz, 1H), 6.97 (t, J = 6.8 Hz, 1H), 4.19 (s, 3H, NCH3), 3.15 (s, 3H, CH3);

13

C{1H} NMR (100 MHz,

CDCl3, ppm) δ 173.6 (C=O), 143.9, 141.3, 140.5, 134.9, 129.2 (2C), 128.5 (2C), 127.7, 127.1, 126.8, 124.5, 123.6, 123.0, 122.8, 121.9, 119.2, 109.1, 34.0 (NCH3), 17.3 (CH3); HRMS calcd. for. C21H18NO2 [M+H]+ 316.1332, found 316.1335. Ethyl 4-([1,1'-biphenyl]-4-yl)-1,9-dimethyl-9H-carbazole-2-carboxylate (7e). Pale yellow solid (33.4 mg, 41% yield), mp 159-161oC. Rf = 0.26 (200:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3) δ 7.76 (t, J = 8.4 Hz, 4H), 7.65 (d, J = 8.0 Hz, 2H), 7.54 (s, 1H), 7.52-7.38 (m, 6H), 6.98 (t, J = 7.4 Hz, 1H), 4.42 (q, J = 7.0 Hz, 2H, OCH2), 4.19 (s, 3H, NCH3), 3.08 (s, 3H, CH3), 1.42 (t, J = 7.0 Hz, 3H, CH3); 13


139.7, 134.5, 129.7 (2C), 129.3, 128.9 (2C), 127.4, 127.1 (4C), 126.5, 123.5, 122.9, 122.6, 122.0, 121.3, 119.1, 109.0, 61.0 (OCH2), 33.8 (NCH3), 17.2 (CH3), 14.4 (OCH2CH3); HRMS calcd. for. C29H26NO2 [M+H]+ 420.1958, found 420.1954. 1,9-Dimethyl-4-phenyl-9H-carbazole (8a). White solid (39.0 mg, 72% yield), mp 114-116 oC. Rf = 0.38 (500:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3, ppm) δ 7.57 (d, J = 8.4 Hz, 2H), 7.52-7.44 (m, 3H), 7.40-7.31 (m, 3H), 7.20 (d, J = 7.2 Hz, 1H), 6.97-6.91 (m, 2H), 4.15 (s, 3H, NCH3), 2.91 (s, 3H, CH3); 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 141.9, 141.5, 139.9, 135.9, 129.3 (2C), 128.6, 128.3 (2C),



127.3, 125.3, 122.5, 122.3, 120.9, 120.7, 119.2, 118.5, 108.3, 32.4 (NCH3), 20.5 (CH3); HRMS calcd. for. C20H18N [M+H]+ 272.1434, found 272.1437. Methyl 9-methyl-4-phenyl-9H-carbazole-1-carboxylate (8b). Pale yellow liquid (37.8 mg, 60% yield). Rf = 0.27 (200:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3) δ 7.90 (d, J = 7.6 Hz, 1H), 7.58-7.50 (m, 5H), 7.44-7.43 (m, 2H), 7.32 (d, J = 8.0 Hz, 1H), 7.10 (d, J = 7.6 Hz, 1H), 7.00-6.96 (m, 1H), 4.03 (s, 3H, NCH3), 3.90 (s, 3H, CH3);

13

C{1H} NMR (100 MHz, CDCl3) δ 168.2 (C=O), 142.8, 141.5, 140.6,

139.6, 128.9 (2C), 128.5 (2C), 128.0, 127.9, 126.2, 122.7, 122.2, 122.2, 120.1, 119.4, 114.0, 109.1, 52.2 (OCH3), 33.6 (NCH3); HRMS calcd. for. C21H18NO2 [M+H]+ 316.1332, found 316.1337. 9-Methyl-4-phenyl-9H-carbazole-1-carbonitrile (8c)15b. White solid (16.9 mg, 30% yield), mp 127-129 oC. Rf = 0.30 (300:1 petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3, ppm) δ 7.76 (d, J = 8.0 Hz, 1H), 7.56-7.56 (m, 5H), 7.50-7.44 (m, 2H), 7.36 (d, J = 8.0 Hz, 1H), 7.10 (d, J = 8.0 Hz, 1H), 7.05-7.01 (m, 1H), 4.27 (s , 3H, NCH3); 13

C{1H} NMR (100 MHz, CDCl3, ppm) δ 142.7, 141.8, 140.3, 139.8, 131.3, 128.7

(2C), 128.7 (2C), 128.4, 126.9, 122.5, 122.2, 121.5, 120.7, 120.0, 119.1, 108.8, 91.6, 30.7 (NCH3); HRMS calcd. for. C20H15N2 [M+H]+ 283.1230, found 283.1238. ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc


Page 32 of 44

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Coordinates and energies for all computed structures (PDF) 1

H NMR and 13C NMR spectra for all products (PDF)

Crystallographic data for the compound 7e (CIF) AUTHOR INFORMATION Corresponding Author *E-mail: [email protected]. *E-mail: [email protected]. Notes The authors declare no competing financial interest. ACKNOWLEDGMENT We are grateful for financial support from the National Natural Science Foundation of China (21871226, 21572194, 21372187), the Collaborative Innovation Center of New Chemical Technologies for Environmental Benignity and Efficient Resource Utilization. REFERENCES (1) (a) Knölker, H.-J.; Reddy, K. R. Isolation and Synthesis of Biologically Active Carbazole Alkaloids. Chem. Rev. 2002, 102, 4303-4428. (b) Schmidt, A. W.; Reddy, K. R.; Knölker, H.-J. Occurrence, Biogenesis, and Synthesis of Biologically Active Carbazole Alkaloids. Chem. Rev. 2012, 112, 3193-3328. (c) Zhang, F. F.; Gan, L. L.; Zhou, C.-H. Synthesis, Antibacterial and Antifungal Activities of Some Carbazole Derivatives. Bioorg. Med. Chem. Lett. 2010, 20, 1881-1884. (d) Ito, C.; Itoigawa, M.; Sato, A.; Hasan, C. M.; Rashid, M. A.; Tokuda, H.; Mukainaka, T.; Nishino, H.;



Furukawa, H. J. Chemical Constituents of Glycosmis arborea: Three New Carbazole Alkaloids and Their Biological Activity. J. Nat. Prod. 2004, 67, 1488-1491. (2) (a) Beaujuge, P. M.; Reynolds, J. R. Color Control in π-Conjugated Organic Polymers for Use in Electrochromic Devices. Chem. Rev. 2010, 110, 268-320. (b) Wang, C.; Dong, H.; Hu, W.; Liu, Y.; Zhu, D. Semiconducting π-Conjugated Systems in Field-Effect Transistors: A Material Odyssey of Organic Electronics. Chem. Rev. 2012, 112, 2208-2267. (c) Díaz, J. L.; Dobarro, A.; Villacampa, B.; Velasco, D. Structure and Optical Properties of 2,3,7,9-Polysubstituted Carbazole Derivatives. Experimental and Theoretical Studies. Chem. Mater. 2001, 13, 2528-2536. (d) Thomas, K. R. J.; Lin, J. T.; Tao, Y. T.; Ko, C. W. Light-Emitting Carbazole Derivatives: Potential Electroluminescent Materials. J. Am. Chem. Soc. 2001, 123, 9404-9411. (e) Dumur, F. Carbazole-Based Polymers as Hosts for Solution-Processed Organic Light-Emitting Diodes: Simplicity, Efficacy. Org. Electron, 2015, 25, 345-361. (f) Lellouche, J.-P.; Koner, R. R.; Ghosh, S. N-Substituted Carbazole Heterocycles and Derivatives as Multipurpose Chemical Species: at the Interface of Chemical Engineering, Polymer and Materials Science. Rev. Chem. Eng. 2013, 29, 413-437. (g) Li, J.; Grimsdale, A. C. Carbazole-Based Polymers for Organic Photovoltaic Devices. Chem. Soc. Rev. 2010, 39, 2399-2410. (h) Grazulevicius, J. V.; Strohriegl, P.; Pielichowski, J.; Pielichowski, K. Carbazole-Containing Polymers: Synthesis, Properties and Applications. Prog. Polym. Sci. 2003, 28, 1297-1353.


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(3) (a) Robinson, B. Studies on the Fischer Indole Synthesis. Chem. Rev. 1969, 69, 227-250. (b) Muller, S.; Webber, M. J.; List, B. The Catalytic Asymmetric Fischer Indolization. J. Am. Chem. Soc. 2011, 133, 18534-18537. (4) (a) Takamatsu, K.; Hirano, K.; Satoh, T.; Miura, M. Synthesis of Carbazoles by Copper-Catalyzed Intramolecular C-H/N-H Coupling. Org. Lett. 2014, 16, 2892-2895. (b) Hesse, R.; Jäger, A.; Schmidt, A. W.; Knölker, H.-J. Palladium(II)-Catalysed total Synthesis of Naturally Occurring Pyrano[3,2-a]Carbazole and Pyrano[2,3-b]Carbazole Alkaloids. Org. Biomol. Chem. 2014, 12, 3866-3876. (c) Ma, D.; Dai, J.; Qiu, Y.; Fu, C.; Ma, S. Gram Scale Synthesis of 7-Methoxy-O-Methylmukonal, Clausine-O, Clausine-K, Clausine-H, 7-Methoxymukonal, and Methyl 2-Hydroxy-7-Methoxy-9HCarbazole-3-Carboxylate. Org. Chem. Front. 2014, 1, 782-791. (d) Li, X.; Song, W.; Tang, W. Rhodium-Catalyzed Tandem Annulation and (5+1) Cycloaddition: 3-Hydroxy-1,4-Enyne as the 5-Carbon Component. J. Am. Chem. Soc. 2013, 135, 16797-16800. (e) Hesse, R.; Krahl, M. P.; Jäger, A.; Kataeva, O.; Schmidt, A. W.; Knölker, H.-J. Palladium(II)-Catalyzed Synthesis of the Formylcarbazole Alkaloids Murrayaline A-C, 7-Methoxymukonal, and 7-Methoxy-O-methylmukonal. Eur. J. Org. Chem. 2014, 19, 4014-4028. (f) Julich-Gruner, K. K.; Kataeva, O.; Schmidt, A. W.; Knölker, H.-J. Total Synthesis of 7-and 8-Oxygenated Pyrano[3,2-a]carbazole and Pyrano[2,3-a]carbazole Alkaloids via Boronic Acid-Catalyzed Annulation of the Pyran Ring. Chem. Eur. J. 2014, 20, 8536-8540. (g) Hesse, R.; Kataeva, O.; Schmidt, A. W.; Knölker, H.-J. Synthesis of Prenyl- and Geranyl-Substituted Carbazole



Alkaloids

by

DIBAL-H

Promoted

Reductive

Pyran

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Ring

Opening

of

Dialkylpyrano[3,2-a]carbazoles. Chem. Eur. J. 2014, 20, 9504-9509. (5) (a) Gassner, C.; Hesse, R.; Schmidt, A. W.; Knölker, H.-J. Total Synthesis of the Cyclic

Monoterpenoid

Pyrano[3,2-a]carbazole

Alkaloids

Derived

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Three-Component Cascade Synthesis of Carbazoles through [1s,6s

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