Skip to main content
NCBI home page
ACS Omega logoLink to ACS Omega
. 2021 Jun 25;6(26):16969–16979. doi: 10.1021/acsomega.1c01992

Synthesis of 4-Hydroxycarbazole Derivatives by Benzannulation of 3-Nitroindoles with Alkylidene Azlactones

Dongdong Cao 1, Gang Chen 1, Dingben Chen 1, Zhijun Xia 1, Zongyang Li 1, Yi Wang 1, Dongqing Xu 1, Jianguo Yang 1,*
PMCID: PMC8264937  PMID: 34250355

Abstract

graphic file with name ao1c01992_0009.jpg

A general synthesis of 4-hydroxylcarbazoles by domino vinylogous conjugate addition/cyclization/elimination/aromatization of easily prepared 3-nitroindoles with alkylidene azlactones under mild and transition-metal-free conditions has been developed. This method was also applicable to other nitrosubstituted benzofused heterocycles such as 3-nitrobenzothiophene, 2-nitrobenzothiophene, and 2-nitrobenzofuran. The valuable tetracyclic carbazole derivatives, such as 6H-oxazolo[4,5-c]carbazole and 3,6-dihydro-2H-oxazolo[4,5-c]carbazol-2-one, were readily prepared from the product, demonstrating synthetic utility of this method.

Introduction

A carbazole nucleus is found in numerous bioactive natural products and pharmaceuticals (Figure 1).1 For example, carbazomycins A and B, which are first isolated from Streptoverticillium ehimense H 1051-MY 10, exhibit antibacterial and antiyeast activities.2 Carvedilol, an FDA-approved nonselective α1- and β-adrenergic blocker, is used clinically for the treatment of angina, hypertension, and symptomatic chronic heart failure.3 Interestingly, the selected examples bear a common 4-oxygenated carbazole core. For this reason, it is highly desirable to develop an efficient general method focusing on 4-hydroxylcarbazole synthesis.

Figure 1.

Figure 1

Open in a new tab

Selected natural products and drug containing a 4-oxygenated carbazole core.

Traditionally, 4-hydroxylcarbazoles can be prepared by dehydrogenation aromatization of tetrahydro-4H-carbazol-4-ones.4 This method is restricted with narrow substrate scope, high reaction temperature, and failure to access substituted 4-hydroxycarbazoles. Recently, owing to ready availability of indoles, synthesis of 4-hydroxylcarbazoles from indole-derived substrates via formation of a phenol ring has emerged as a powerful strategy.5 To date, a variety of indolyl compounds have been prepared from indoles to serve as a four-,6 five-,7 six-carbon8 synthon (Scheme 1A). These methods suffer from multistep synthesis of the substrates, high reaction temperature, and/or use of transition metals. In contrast, an indole-derived two-carbon synthon such as 3-nitroindoles9 can be easily prepared from indoles in only two steps.10 However, to our knowledge, examples of 4-hydroxylcarbazole synthesis using 3-nitroindoles are scarce. Moreno and co-workers reported that a microwave-assisted reaction of 3-nitroindole with a mixture of 1-methoxy-1,3-cyclohexadiene and 2-methoxy-1,3-cyclohexadiene furnished an inseparable mixture of 4-methoxycarbazole and 2-methoxycarbazole (Scheme 1B).11 Unsubstituted 4-hydroxycarbazole was obtained by the reaction of 3-nitroindole with 1-trimethylsilyloxy-1,3-butadiene in protic ionic liquids (Scheme 1C).12 Obviously, these two methods suffer from narrow substrate scope (single example) and fail to access substituted products. Huang, Li, and co-workers developed [4 + 2] annulation of 3-nitroindoles with enals by oxidative NHC catalysis to access hydrocarbazolones, which require further basic treatment to give monosubstituted 4-hydroxylcarbazole (Scheme 1D).13 Alkylidene azlactones,14−16 a class of vinylogous nucleophiles,17 can serve as a four-carbon synthon to react with activated carbonyl compounds or alkenes to furnish three-dimensional α,β-unsaturated δ-lactone15a,15b,15d or cyclohexenone15c derivatives, respectively. To our knowledge, synthesis of planar aromatic compounds using alkylidene azlactones has not been reported. Inspired by a previous work15 and our continuous interest in the synthesis of carbazoles using 3-nitroindoles,18 we envisaged that 4-hydroxycarbazoles could be synthesized by a base-promoted reaction of 3-nitroindoles with alkylidene azlactones (Scheme 1E). This protocol features broad substrate scope and no need for catalysts and oxidants. Moreover, the concomitant amino and hydroxyl groups in products can serve as synthetic handles to prepare valuable tetracyclic carbazole derivatives. Herein, we wish to report a facile general method for the synthesis of 4-hydroylcarbazole derivatives.

Scheme 1. (A–E) Methods for 4-Hydroxylcarbazoles Synthesis Starting from Indolyl Compounds.

Scheme 1

Open in a new tab

Results and Discussion

At the outset of our study, N-Ts-3-nitroindole 1a and acetophenone-derived alkylidene azlactone 2a were selected as model substrates (Table 1). When performed in CH3CN using K2CO3 as a base at 40 °C, the reaction was completed within 24 h and successfully furnished the desired product 3aa in 28% yield (entry 1). The low yield is attributed to the generation of a large amount of byproduct 3aa′,19 which was formed by further O-tosylation of 3aa with 1a. The reaction in CH2Cl2 and PhMe, respectively, became slow, and 3aa was obtained in still low yield because of the presence of unreacted starting substrates and 3aa′ (entries 2 and 3). Among etheric solvents screened, THF proved optimal in terms of yield (entries 4–7). Actually, the reaction in THF was completed, and its modest yield was mainly caused by the formation of 3aa′. The phenomena prompted us to improve yield by inhibiting formation of 3aa′. We noticed that 3aa′ generated in PhMe was negligible and reasoned that a nonpolar solvent was detrimental to its formation. In this direction, further screening of THF mixed with a nonpolar solvent was performed (entries 8–11) and showed that THF/hexane (1:2) gave the highest 85% yield (entry 11). Next, we investigated the effect of base on yield. The reaction promoted by Et3N and Na2CO3 (entries 12 and 13), respectively, failed to furnish 3aa due to their weak basicity. 3aa was obtained in 52% yield in the presence of Cs2CO3 (entry 14). The structure of 3aa was confirmed by single-crystal X-ray analysis (see the Supporting Information).20 Thus, the optimal reaction conditions found were the use of K2CO3 in THF/hexane (1:2) at 40 °C.

Table 1. Optimization of Reaction Conditionsa.

graphic file with name ao1c01992_0006.jpg

entry base solvent yield (%)b
1 K2CO3 CH3CN 28
2 K2CO3 CH2Cl2 29
3 K2CO3 PhMe 14
4 K2CO3 THF 60
5 K2CO3 tBuOMe 54
6 K2CO3 dioxane 50
7 K2CO3 2-MeTHF 46
8 K2CO3 THF/PhCH3 (1:1) 67
9 K2CO3 THF/PhCH3 (1:2) 75
10 K2CO3 THF/PhCH3 (1:3) 60
11 K2CO3 THF/hexane (1:2) 85
12 Et3N THF/hexane (1:2) NRd
13 Na2CO3 THF/hexane (1:2) trace
14c Cs2CO3 THF/hexane (1:2) 52
Open in a new tab
a

Reaction conditions: 3-nitroindole 1a (0.20 mmol), alkylidene azlactone 2a (0.24 mmol, 1.2 equiv), and K2CO3 (0.40 mmol, 2.0 equiv) in solvent (4 mL) at 40 °C for 24 h.

b

Isolated yields.

c

5 h.

d

NR = No reaction.

After establishing the optimal conditions, we set out to first investigate alkylidene azlactone scope.21 As depicted in Table 2, a variety of alkylidene azlactones 2b–2l bearing electron-donating or electron-withdrawing groups at benzene ring’s C-4 position reacted smoothly with 1a to furnish the corresponding 4-hydroxylcarbazoles 3ab–3al in moderate to good yields. Generally, the products from alkylidene azlactones with electron-donating groups were obtained in lower yields. This is due to the fact that they show high reactivity toward 1a, and more byproducts were concomitantly formed (vide infra). Condensed 2-acetonaphthone-derived 2m furnished 3am in 63% yield. The reaction temperature was elevated to 60 °C in the case of 2n because of its weak acidity, and 3an was obtained in 24% yield. To our delight, acetone-derived 2o smoothly afforded 3ao in 32% yield. Electron-donating and electron-withdrawing groups at benzene ring’s 3-position were all tolerated, and the corresponding 3ap–3as were obtained in moderate to good yields. 3at was obtained in 20% yield in the case of 2t.

Table 2. Alkylidene Azlactones Scopea.

graphic file with name ao1c01992_0007.jpg

Open in a new tab
a

Reaction conditions: 3-nitroindole 1a (0.20 mmol), alkylidene azlactone 2 (0.24 mmol, 1.2 equiv), and K2CO3 (0.40 mmol, 2.0 equiv) in THF/hexane (1:2, 4 mL) at 40 °C for 24 h. Isolated yield.

b

60 °C.

c

36 h.

Next, a variety of 3-nitroindoles were prepared and evaluated. As shown in Table 3, owing to a sterically hindered methyl group present at the C4 position, the reaction of 1b was performed at 60 °C, which gave 3ba in 53% yield. 5-Methyl-3-nitroindole 1c afforded 3ca in 92% yield. In contrast, 3da was obtained in 43% yield in the case of 6-chloro-3-nitroindole 1d. This is attributed to the fact that the substrate 1d could serve as a more reactive tosylated reagent toward 3da, and more byproducts were concomitantly formed (vide supra). We also investigated the effect of the protecting group at the N-1 position of 1. Reactions of N-Ac-3-nitroindole 1e and N-Boc-3-nitroindole 1f proceeded smoothly. However, N-methyl 3-nitroindole 1g proved to be unreactive, probably due to its decreased electrophilicity. These outcomes indicate that an electron-withdrawing group at the N-1 position of 3-nitroindole is necessary for reactivity. To our delight, this protocol was successfully extended to other nitrosubstituted benzofused heterocycles.22 For example, 3-nitrobenzothiophene 1h, 2-nitrobenzothiophene 1i, and 2-nitrobenzofuran 1j afforded the corresponding compounds 3ha–3ja in moderate to good yields. Harsh conditions were usually required in these cases due to low reactivity.

Table 3. Nitroheteroaromatic Scopea.

graphic file with name ao1c01992_0008.jpg

Open in a new tab
a

Reaction conditions: nitroheteroaromatic 1 (0.20 mmol), alkylidene azlactone 2a (0.24 mmol, 1.2 equiv), and K2CO3 (0.40 mmol, 2.0 equiv) in THF/hexane (1:2, 4 mL) at 40 °C for 24 h.

b

60 °C.

c

36 h.

d

Cs2CO3 (2.0 equiv), 12 h.

Based on the experimental results and the reported literature,13,23 the mechanism proposed for the synthesis of 4-hydroxylcarbazole derivatives 3 is depicted in Scheme 2. The alkylidene azlactone 2 was first deprotonated by K2CO3 to produce dienolate A, which reacted with 3-nitroindoles 1 via vinylogous conjugate addition to give nitronate intermediate B. Then, the intermediate B underwent intramolecular cyclization to give indoline-fused compound C. The compound C was not observed in our reaction systems but was instantly subjected to elimination of nitrous acid to access the indole-fused compound D, which delivered potassium carbazol-4-olate E by aromatization. The product 3 was finally obtained upon acidification.

Scheme 2. Proposed Mechanism of the Reaction.

Scheme 2

Open in a new tab

We also attempted a gram-scale synthesis of 3aa, and the compound was successfully obtained in 79% yield (Scheme 3). 3aa reacted with CH3I under basic conditions to afford compound 4 in 99% yield, which then underwent Ts-deprotection in the presence of TBAF24 to access compound 5 in 90% yield. Benefiting from the presence of amino and hydroxyl groups, the product 3 can be readily converted into valuable tetracyclic carbazole derivatives. For example, 6H-oxazolo[4,5-c]carbazole derivative 6 was obtained in 97% yield via MeSO3H-promoted cyclization of 3aa.25 Interestingly, the compound 6 is a core structure of organic light-emitting devices.26 Moreover, the removal of a benzoyl group27 and cyclization28 of 3aa gave 3,6-dihydro-2H-oxazolo[4,5-c]carbazol-2-one derivative 7 in 53% yield over two steps, which possibly find application in pharmaceutical research.29

Scheme 3. Gram-Scale Synthesis and Transformations of 3aa.

Scheme 3

Open in a new tab

Conclusions

In summary, we have developed a facile approach to accessing valuable 4-hydroxycarbazole derivatives by vinylogous conjugate addition/cyclization/elimination/aromatization of easily available 3-nitroindoles and alkylidene azlactones. This method can be extended to other nitrosubstituted benzofused heterocycles. The obtained products can be readily converted into tetracyclic carbazole derivatives of material and medicinal interest, such as 6H-oxazolo[4,5-c]carbazole and 3,6-dihydro-2H-oxazolo[4,5-c]carbazol-2-one. In addition, the current work represents the first example of synthesis of planar aromatic compounds using alkylidene azlactones and extends their synthetic application in organic synthesis.

Experimental Section

General Information

All reactions were carried out in oven-dried glassware. All reagents and dry solvents were directly used as received. 1H and 13C NMR spectra were recorded in CDCl3 or DMSO-d6 on an AVANCE III HD 400 (1H NMR at 400 MHz, 13C NMR at 100 MHz, and 19F NMR at 376 MHz) spectrometer. 1H NMR data are reported as follows: chemical shift, multiplicity (br = broad, s = singlet, d = doublet, dd = doublet of doublet, dt = doublet of triplet, t = triplet, and m = multiplet), coupling constants (Hz), and integration. Chemical shifts are reported in parts per million relative to TMS, chloroform, or DMSO-d6 (1H, δ 0.00; 13C, δ 77.0 or 39.5 ppm). Melting points were obtained from an X-4 digital micro melting point apparatus and uncorrected. High-resolution mass spectra analysis was performed on a Waters SYNAPT G2-Si mass spectrometer by ESI (electrospray ionization). Flash column chromatography was performed using silica gel (300–400 mesh). For thin-layer chromatography, silica gel plates (HSGF 254) were used, and compounds were visualized by irradiation with UV light (254 nm). 3-Nitroindoles 1a–1g,10a 3-nitrobenzo[b]thiophene 1h,30 2-nitrobenzo[b]thiophene 1i,30 2-nitrobenfuran 1j,31 and alkylidene azlactones 2(32) (Z/E > 20:1) were prepared according to the known procedures.

General Procedure for the Synthesis of 4-Hydroxylcarbazole Derivatives 3

Unless otherwise noted, to a mixture of 1 (0.2 mmol) and 2 (0.24 mmol, 1.2 equiv) in dry THF/hexane (1:2 v/v, 4 mL) was added K2CO3 (0.4 mmol, 2.0 equiv) under a N2 atmosphere. The mixture was stirred at 40 °C (oil bath) for an indicated time. After cooling to room temperature, the mixture was added to aqueous HCl (1 M, 2 mL) and stirred for a few minutes. The volatile solvent was removed in vacuo, and H2O (10 mL) was added. The aqueous solution was extracted with CH2Cl2 (10 mL × 3). The combined organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel to give the target compound 3.

Procedure for Gram-Scale Synthesis of 3aa

To a mixture of 1a (1.107 g, 3.5 mmol) and 2a (1.105 g, 4.2 mmol) in dry THF/hexane (1:2 v/v, 70 mL) was added K2CO3 (0.966 g, 7 mmol, 2.0 equiv) under a N2 atmosphere. The mixture was stirred at 40 °C (oil bath) for 60 h. After cooling to room temperature, the mixture was added to aqueous HCl (1 M, 20 mL) and stirred for a few minutes. The volatile solvent was removed in vacuo, and H2O (100 mL) was added. The aqueous solution was extracted with CH2Cl2 (100 mL) three times. The combined organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (petroleum ether/CH2Cl2 = 1:1) on silica gel to give 3aa (1.48 g, 79% yield).

N-(4-Hydroxy-2-phenyl-9-tosyl-9H-carbazol-3-yl)benzamide (3aa)

Following the general procedure, 3aa was prepared from 1a (63.3 mg, 0.2 mmol) and 2a (63.2 mg, 0.24 mmol) in 24 h. 3aa was isolated by column chromatography (CH2Cl2/petroleum ether = 1:1) as a white solid (90.2 mg, 85% yield), mp = 220–221 °C. 1H NMR (400 MHz, CDCl3): δ 10.34 (br s, 1H), 8.43 (d, J = 7.2 Hz, 1H), 8.30 (d, J = 8.0 Hz, 1H), 7.99 (br s, 1H), 7.90 (s, 1H), 7.68 (d, J = 8.4 Hz, 2H), 7.60–7.46 (m, 9H), 7.42–7.37 (m, 3H), 7.11 (d, J = 8.0 Hz, 2H), 2.28 (s, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 166.7, 146.5, 145.0, 138.2, 138.1, 137.5, 135.1, 134.7, 132.5, 132.2, 129.8, 129.7, 129.2, 128.9, 128.5, 127.2, 126.7, 126.4, 126.1, 124.2, 123.7, 118.7, 117.3, 114.4, 108.2, 21.5 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C32H24N2NaO4S+ 555.1349; Found 555.1358.

N-(4-Hydroxy-2-(p-tolyl)-9-tosyl-9H-carbazol-3-yl)benzamide (3ab)

Following the general procedure, 3ab was prepared from 1a (63.3 mg, 0.2 mmol) and 2b (66.6 mg, 0.24 mmol) in 24 h. 3ab was isolated by column chromatography (CH2Cl2/petroleum ether = 1:1) as a white solid (55.0 mg, 50% yield). mp = 210–211 °C. 1H NMR (400 MHz, CDCl3) δ 10.30 (br s, 1H), 8.41 (d, J = 7.6 Hz, 1H), 8.30 (d, J = 8.4 Hz, 1H), 8.05 (br s, 1H), 7.87 (d, J = 7.8 Hz, 1H), 7.67 (d, J = 8.0 Hz, 2H), 7.56 (d, J = 7.6 Hz, 2H), 7.53–7.45 (m, 2H), 7.40–7.35 (m, 7H), 7.10 (d, J = 8.4 Hz, 2H), 2.48 (s, 3H), 2.27 (s, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 166.7, 146.4, 144.9, 138.4, 138.1, 137.5, 135.1, 134.7, 132.5, 132.2, 129.8, 129.7, 129.6, 128.8, 127.2, 126.6, 126.4, 126.2, 124.1, 123.7, 118.8, 117.1, 114.4, 108.2, 21.4, 21.3 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C33H26N2NaO4S+ 569.1505; Found 569.1515.

N-(4-Hydroxy-2-(4-methoxyphenyl)-9-tosyl-9H-carbazol-3-yl)benzamide (3ac)

Following the general procedure, 3ac was prepared from 1a (63.3 mg, 0.2 mmol) and 2c (70.4 mg, 0.24 mmol) in 24 h. 3ac was isolated by column chromatography (CH2Cl2/petroleum ether = 2:1) as a white solid (53.2 mg, 47% yield). mp = 229–230 °C. 1H NMR (400 MHz, CDCl3) δ 10.29 (br s, 1H), 8.43 (d, J = 7.2 Hz, 1H), 8.30 (d, J = 8.4 Hz, 1H), 8.04 (br s, 1H), 7.87, 7.68 (d, J = 8.4 Hz, 2H), 7.61 (d, J = 7.2 Hz, 2H), 7.54 (t, J = 7.4 Hz, 1H), 7.50–7.38 (m, 6H), 7.11 (d, J = 8.0 Hz, 2H), 7.08 (d, J = 8.8 Hz, 2H), 3.92 (s, 3H), 2.28 (s, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 166.7, 159.7, 146.5, 144.9, 138.1, 137.5, 134.9, 134.7, 132.5, 132.2, 131.0, 130.2, 129.6, 128.8, 127.2, 126.6, 126.4, 126.2, 124.2, 123.6, 118.8, 117.0, 114.5, 114.4, 108.3, 55.4, 21.5 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C33H26N2NaO5S+ 585.1455; Found 585.1464.

N-(2-([1,1′-Biphenyl]-4-yl)-4-hydroxy-9-tosyl-9H-carbazol-3-yl)benzamide (3ad)

Following the general procedure, 3ad was prepared from 1a (63.3 mg, 0.2 mmol) and 2d (81.5 mg, 0.24 mmol) in 24 h. 3ad was isolated by column chromatography (CH2Cl2/petroleum ether = 1:1) as a white solid (69.3 mg, 57% yield). mp = 270–272 °C. 1H NMR (400 MHz, CDCl3) δ 10.28 (br s, 1H), 8.45 (d, J = 7.2 Hz, 1H), 8.31 (d, J = 8.4 Hz, 1H), 8.05 (br s, 1H), 7.95 (s, 1H), 7.80 (d, J = 8.4 Hz, 2H), 7.70 (d, J = 8.0 Hz, 4H), 7.61–7.58 (m, 4H), 7.55–7.37 (m, 8H), 7.12 (d, J = 8.0 Hz, 2H), 2.29 (s, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 166.8, 146.7, 145.0, 141.4, 140.2, 138.2, 137.7, 137.1, 134.8, 134.7, 132.6, 132.3, 130.3, 129.7, 129.0, 129.0, 127.9, 127.8, 127.3, 127.1, 126.8, 126.5, 126.1, 124.3, 123.8, 118.7, 117.4, 114.5, 108.3, 21.5 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C38H28N2NaO4S+ 631.1662; Found 631.1671.

N-(4-Hydroxy-2-(4-(methylthio)phenyl)-9-tosyl-9H-carbazol-3-yl)benzamide (3ae)

Following the general procedure, 3ae was prepared from 1a (63.3 mg, 0.2 mmol) and 2e (74.3 mg, 0.24 mmol) in 24 h. 3ae was isolated by column chromatography (CH2Cl2/petroleum ether = 1:1) as a white solid (88.5 mg, 76% yield). mp = 239–241 °C. 1H NMR (400 MHz, CDCl3) δ 10.18 (br s, 1H), 8.42 (d, J = 7.2 Hz, 1H), 8.30 (d, J = 8.4 Hz, 1H), 8.00 (br s, 1H), 7.87 (s, 1H), 7.67 (d, J = 8.0 Hz, 2H), 7.61–7.59 (m, 2H), 7.55 (t, J = 7.4 Hz, 1H), 7.48 (dt, J = 1.2, 7.2 Hz, 1H), 7.44–7.38 (m, 7H), 7.12 (d, J = 8.0 Hz, 2H), 2.58 (s, 3H), 2.28 (s, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 166.8, 146.6, 145.0, 139.6, 138.1, 137.6, 134.7, 134.6, 134.5, 132.6, 132.1, 130.2, 129.7, 128.9, 127.3, 126.7, 126.4, 126.1, 124.2, 123.7, 118.7, 117.3, 114.4, 108.2, 21.5, 15.6 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C33H26N2NaO4S2+ 601.1226; Found 601.1224.

N-(2-(4-Fluorophenyl)-4-hydroxy-9-tosyl-9H-carbazol-3-yl)benzamide (3af)

Following the general procedure, 3af was prepared from 1a (63.3 mg, 0.2 mmol) and 2f (67.5 mg, 0.24 mmol) in 24 h. 3af was isolated by column chromatography (CH2Cl2/petroleum ether = 1:1) as a white solid (70.0 mg, 64% yield). mp = 207–209 °C. 1H NMR (400 MHz, CDCl3) δ 10.14 (br s, 1H), 8.40 (d, J = 7.6 Hz, 1H), 8.29 (d, J = 8.4 Hz, 1H), 7.91 (br s, 1H), 7.85 (s, 1H), 7.67 (d, J = 8.4 Hz, 2H), 7.57–7.46 (m, 6H), 7.42–7.37 (m, 3H), 7.25 (t, J = 8.4 Hz, 2H), 7.11 (d, J = 8.0 Hz, 2H), 2.28 (s, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 166.8, 162.8 (d, JC-F = 247.4 Hz), 146.7, 145.0, 137.8 (d, JC-F = 52.0 Hz), 134.7, 134.12 (d, JC-F = 3.4 Hz), 134.05, 132.7, 132.0, 131.7, 131.6, 129.7, 128.9, 127.1, 126.8, 126.4, 126.0, 124.2, 123.7, 118.7, 117.4, 116.3, 116.1, 114.4, 108.3, 21.5 ppm. 19F NMR (376 MHz, CDCl3) δ −112.7 (m) ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C32H23FN2NaO4S+ 573.1255; Found 573.1271.

N-(2-(4-Chlorophenyl)-4-hydroxy-9-tosyl-9H-carbazol-3-yl)benzamide (3ag)

Following the general procedure, 3ag was prepared from 1a (63.3 mg, 0.2 mmol) and 2g (71.4 mg, 0.24 mmol) in 24 h. 3ag was isolated by column chromatography (CH2Cl2/petroleum ether = 1:1) as a white solid (70.0 mg, 62% yield). mp = 231–232 °C. 1H NMR (400 MHz, CDCl3) δ 10.06 (br s, 1H), 8.41 (d, J = 7.6 Hz, 1H), 8.29 (d, J = 8.4 Hz, 1H), 7.90 (br s, 1H), 7.85 (s, 1H), 7.66 (d, J = 8.4 Hz, 2H), 7.59–7.38 (m, 11H), 7.11 (d, J = 8.4 Hz, 2H), 2.28 (s, 2H) ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 166.9, 146.8, 145.1, 138.1, 137.6, 136.6, 134.7, 133.8, 132.7, 132.0, 131.1, 129.7, 129.4, 129.0, 127.2, 126.9, 126.4, 125.9, 124.3, 123.8, 118.5, 117.6, 114.4, 108.3, 21.5 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C32H2335ClN2NaO4S+ 589.0959; Found 589.0969.

N-(2-(4-Bromophenyl)-4-hydroxy-9-tosyl-9H-carbazol-3-yl)benzamide (3ah)

Following the general procedure, 3ah was prepared from 1a (63.3 mg, 0.2 mmol) and 2h (82.1 mg, 0.24 mmol) in 24 h. 3ah was isolated by column chromatography (CH2Cl2/petroleum ether = 1:1) as a white solid (77.0 mg, 63% yield). mp = 247–248 °C. 1H NMR (400 MHz, CDCl3) δ 10.06 (br s, 1H), 8.42 (d, J = 7.2 Hz, 1H), 8.29 (d, J = 8.4 Hz, 1H), 7.89 (br s, 1H), 7.85 (s, 1H), 7.70–7.65 (m, 4H), 7.60–7.54 (m, 3H), 7.51–7.38 (m, 6H), 7.11 (d, J = 8.0 Hz, 2H), 2.28 (s, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 166.9, 146.8, 145.1, 138.2, 137.7, 137.1, 134.7, 133.8, 132.8, 132.4, 132.1, 131.5, 129.7, 129.1, 127.2, 126.9, 126.4, 125.9, 124.3, 123.8, 122.9, 118.5, 117.6, 114.5, 108.2, 21.5 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C32H2379BrN2NaO4S+ 633.0454; Found 633.0463.

N-(4-Hydroxy-2-(4-iodophenyl)-9-tosyl-9H-carbazol-3-yl)benzamide (3ai)

Following the general procedure, 3ai was prepared from 1a (63.3 mg, 0.2 mmol) and 2i (93.4 mg, 0.24 mmol) in 24 h. 3ai was isolated by column chromatography (CH2Cl2/petroleum ether = 1:1) as a white solid (79.5 mg, 60% yield). mp = 257–258 °C. 1H NMR (400 MHz, CDCl3) δ 10.06 (s, 1H), 8.43 (d, J = 7.2 Hz, 1H), 8.30 (d, J = 8.4 Hz, 1H), 7.91–7.88 (m, 3H), 7.85 (s, 1H), 7.66 (d, J = 8.4 Hz, 2H), 7.60–7.55 (m, 3H), 7.51–7.39 (m, 4H), 7.26 (d, J = 8.4 Hz, 2H), 7.11 (d, J = 8.0 Hz, 2H), 2.28 (s, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 166.9, 146.8, 145.1, 138.3, 138.2, 137.7, 137.7, 134.7, 133.9, 132.7, 132.1, 131.7, 129.7, 129.1, 127.2, 126.9, 126.4, 125.9, 124.3, 123.8, 118.4, 117.6, 114.5, 108.1, 94.4, 21.5 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C32H23IN2NaO4S+ 681.0315; Found 681.0324.

N-(4-Hydroxy-2-(4-nitrophenyl)-9-tosyl-9H-carbazol-3-yl)benzamide (3aj)

Following the general procedure, 3aj was prepared from 1a (63.3 mg, 0.2 mmol) and 2j (74.0 mg, 0.24 mmol) in 24 h. 3aj was isolated by column chromatography (CH2Cl2/petroleum ether = 5:1) as a white solid (96.9 mg, 84% yield). mp = 267–268 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.35 (br s, 1H), 9.73 (br s, 1H), 8.27–8.23 (m, 4H), 7.81–7.56 (m, 7H), 7.60–7.43 (m, 5H), 7.35 (d, J = 8.4 Hz, 2H), 2.29 (s, 3H) ppm. 13C{1H} NMR (100 MHz, DMSO-d6) δ 166.7, 150.6, 146.8, 146.6, 145.9, 138.9, 137.4, 137.3, 134.3, 133.6, 131.4, 130.3, 130.2, 128.1, 127.7, 127.2, 126.3, 125.1, 124.6, 123.2, 123.0, 118.1, 114.8, 114.2, 106.3, 21.1 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C32H23N3NaO6S+ 600.1200; Found 600.1204.

N-(2-(4-Cyanophenyl)-4-hydroxy-9-tosyl-9H-carbazol-3-yl)benzamide (3ak)

Following the general procedure, 3ak was prepared from 1a (63.3 mg, 0.2 mmol) and 2k (69.2 mg, 0.24 mmol) in 24 h. 3ak was isolated by column chromatography (CH2Cl2/petroleum ether = 5:1) as a white solid (102.1 mg, 92% yield). mp = 237–238 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.32 (br s, 1H), 9.69 (br s, 1H), 8.26 (dd, J = 4.0, 8.0 Hz, 4H), 7.87 (d, J = 8.4 Hz, 2H), 7.81–7.78 (m, 4H), 7.73 (s, 2H), 7.71 (s, 1H), 7.59–7.51 (m, 2H), 7.48–7.43 (m, 3H), 7.34 (d, J = 8.4 Hz, 2H), 2.28 (s, 3H) ppm. 13C{1H} NMR (100 MHz, DMSO-d6) δ 166.7, 150.6, 145.9, 144.8, 139.4, 137.4, 137.3, 134.4, 133.6, 132.0, 131.3, 130.3, 129.9, 128.1, 127.7, 127.1, 126.3, 125.1, 124.6, 123.0, 118.9, 118.1, 114.6, 114.2, 110.0, 106.2, 21.1 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C33H23N3NaO4S+ 580.1301; Found 580.1312.

Methyl 4-(3-Benzamido-4-hydroxy-9-tosyl-9H-carbazol-2-yl)benzoate (3al)

Following the general procedure, 3al was prepared from 1a (63.3 mg, 0.2 mmol) and 2l (77.1 mg, 0.24 mmol) in 24 h. 3al was isolated by column chromatography (CH2Cl2/petroleum ether = 5:1) as a white solid (96.3 mg, 82% yield). mp = 189–191 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.26 (br s, 1H), 9.69 (br s, 1H), 8.28–8.24 (m, 2H), 7.96 (d, J = 8.4 Hz, 2H), 7.81–7.78 (m, 4H), 7.74 (s, 1H), 7.68 (d, J = 8.4 Hz, 2H), 7.59–7.50 (m, 2H), 7.48–7.42 (m, 3H), 7.34 (d, J = 8.4 Hz, 2H), 3.84 (s, 3H), 2.28 (s, 3H) ppm. 13C{1H} NMR (100 MHz, DMSO-d6) δ 166.7, 166.1, 150.5, 145.9, 144.7, 139.9, 137.4, 137.3, 134.4, 133.6, 131.3, 130.3, 129.3, 128.9, 128.3, 128.1, 127.8, 127.0, 126.3, 125.2, 124.5, 122.9, 118.1, 114.4, 114.2, 106.2, 52.2, 21.0 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C34H26N2NaO6S+ 613.1404; Found 613.1417.

N-(4-Hydroxy-2-(naphthalen-2-yl)-9-tosyl-9H-carbazol-3-yl)benzamide (3am)

Following the general procedure, 3am was prepared from 1a (63.3 mg, 0.2 mmol) and 2m (75.2 mg, 0.24 mmol) in 24 h. 3am was isolated by column chromatography (CH2Cl2/petroleum ether = 1:1) as a white solid (73.0 mg, 63% yield). mp = 212–213 °C. 1H NMR (400 MHz, CDCl3) δ 10.28 (br s, 1H), 8.46 (d, J = 7.2 Hz, 1H), 8.32 (d, J = 8.4 Hz, 1H), 8.07 (br s, 1H), 8.03–7.91 (m, 5H), 7.69 (d, J = 8.0 Hz, 2H), 7.64–7.59 (m, 3H), 7.54–7.39 (m, 5H), 7.30 (t, J = 7.8 Hz, 2H), 7.12 (d, J = 8.0 Hz, 2H), 2.29 (s, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 166.9, 146.7, 145.0, 138.2, 137.7, 135.5, 135.0, 134.8, 133.4, 132.9, 132.5, 132.2, 129.7, 129.1, 128.9, 128.9, 128.1, 127.9, 127.5, 127.2, 127.0, 126.9, 126.7, 126.5, 126.1, 124.2, 123.8, 118.8, 117.4, 114.5, 108.6, 21.5 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C36H26N2NaO4S+ 605.1505; Found 605.1520.

N-(4-Hydroxy-2-(thiophen-2-yl)-9-tosyl-9H-carbazol-3-yl)benzamide (3an)

Following the general procedure, 3an was prepared from 1a (63.3 mg, 0.2 mmol) and 2n (64.6 mg, 0.24 mmol) at 60 °C in 24 h. 3an was isolated by column chromatography (CH2Cl2/petroleum ether = 1:1) as a white solid (25.4 mg, 24% yield). mp = 189–190 °C. 1H NMR (400 MHz, CDCl3) δ 10.28 (br s, 1H), 8.44 (d, J = 7.2 Hz, 1H), 8.36 (br s, 1H), 8.30 (d, J = 8.4 Hz, 1H), 8.03 (s, 1H), 7.70 (t, J = 8.2 Hz, 4H), 7.59–7.54 (m, 2H), 7.51–7.45 (m, 3H), 7.40 (t, J = 7.6 Hz, 1H), 7.24 (m, 2H), 7.12 (d, J = 8.4 Hz, 2H), 2.28 (s, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 166.7, 146.5, 145.0, 139.3, 138.2, 137.3, 134.6, 132.7, 132.1, 129.7, 129.0, 128.0, 127.9, 127.5, 127.4, 127.2, 126.9, 126.5, 126.0, 124.3, 123.8, 119.1, 117.9, 114.5, 109.1, 21.5 ppm. HRMS (ESI) m/z: [M + Na]+ Calcd for C30H22N2NaO4S2+ 561.0913; Found 561.0922.

N-(4-Hydroxy-2-methyl-9-tosyl-9H-carbazol-3-yl)benzamide (3ao)

Following the general procedure, 3ao was prepared from 1a (63.3 mg, 0.2 mmol) and 2o (48.3 mg, 0.24 mmol) in 36 h. 3ag was isolated by column chromatography (CH2Cl2/petroleum ether = 1:1) as a white solid (29.9 mg, 32% yield). mp = 247–248 °C. 1H NMR (400 MHz, CDCl3) δ 9.39 (br s, 1H), 8.35 (d, J = 7.2 Hz, 1H), 8.25 (d, J = 9.0 Hz, 1H), 7.94–7.92 (m, 3H), 7.80 (s, 1H), 7.66 (d, J = 8.4 Hz, 2H), 7.61 (t, J = 7.4 Hz, 1H), 7.53 (t, J = 7.6 Hz, 2H), 7.43 (t, J = 7.6 Hz, 1H), 7.35 (t, J = 7.2 Hz, 1H), 7.09 (d, J = 8.0 Hz, 2H), 2.55 (s, 3H), 2.26 (s, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 167.2, 146.5, 144.9, 137.8, 137.7, 134.8, 132.8, 132.7, 130.2, 129.6, 129.0, 127.3, 126.4, 126.3, 126.2, 124.1, 123.4, 119.9, 116.3, 114.4, 108.5, 21.5, 19.5 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C27H22N2NaO4S+ 493.1192; Found 493.1197.

N-(4-Hydroxy-2-(m-tolyl)-9-tosyl-9H-carbazol-3-yl)benzamide (3ap)

Following the general procedure, 3ap was prepared from 1a (63.3 mg, 0.2 mmol) and 2p (66.6 mg, 0.24 mmol) in 24 h. 3ap was isolated by column chromatography (CH2Cl2/petroleum ether = 1:1) as a white solid (79.0 mg, 72% yield). mp = 213–214 °C. 1H NMR (400 MHz, CDCl3) δ 10.40 (br s, 1H), 8.44 (d, J = 7.2 Hz, 1H), 8.30 (d, J = 8.0 Hz, 1H) 8.04 (br s, 1H), 7.90 (s, 1H), 7.68 (d, J = 8.4 Hz, 2H), 7.57–7.4 4 (m, 5H), 7.42–7.38 (m, 3H), 7.35–7.29 (m, 3H), 7.11 (d, J = 8.0 Hz, 2H), 2.45, 2.28 ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 166.7, 146.5, 144.9, 139.1, 138.1, 138.1, 137.6, 135.2, 134.8, 132.6, 132.4, 130.6, 129.7, 129.3, 129.1, 128.9, 127.2, 126.9, 126.7, 126.5, 126.2, 124.2, 123.7, 118.8, 117.2, 114.5, 108.1, 21.49, 21.47 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C33H26N2NaO4S+ 569.1505; Found 569.1514.

N-(2-(3-Bromophenyl)-4-hydroxy-9-tosyl-9H-carbazol-3-yl)benzamide (3aq)

Following the general procedure, 3aq was prepared from 1a (63.3 mg, 0.2 mmol) and 2q (82.1 mg, 0.24 mmol) in 24 h. 3aq was isolated by column chromatography (CH2Cl2/petroleum ether = 1:1) as a white solid (60.6 mg, 50% yield). mp = 210–211 °C. 1H NMR (400 MHz, CDCl3) δ 10.22 (br s, 1H), 8.44 (d, J = 7.6 Hz, 1H), 8.30 (d, J = 8.0 Hz, 1H), 7.90 (br s, 1H), 7.88 (s, 1H), 7.70–7.67 (m, 4H), 7.61 (d, J = 7.6 Hz, 2H), 7.56 (t, J = 7.4 Hz, 1H), 7.51–7.39 (m, 6H), 7.13 (d, J = 8.4 Hz, 2H), 2.29 (s, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 167.1, 146.9, 145.1, 140.3, 138.2, 137.6, 134.7, 133.5, 132.8, 132.7, 132.2, 131.6, 130.7, 129.7, 129.0, 128.6, 127.3, 126.9, 126.4, 125.9, 124.3, 123.8, 123.2, 118.5, 117.7, 114.5, 108.2, 21.5 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C32H2379BrN2NaO4S+ 633.0454; Found 633.0455.

N-(2-(3-Chlorophenyl)-4-hydroxy-9-tosyl-9H-carbazol-3-yl)benzamide (3ar)

Following the general procedure, 3ar was prepared from 1a (63.3 mg, 0.2 mmol) and 2r (71.4 mg, 0.24 mmol) in 24 h. 3ar was isolated by column chromatography (CH2Cl2/petroleum ether = 1:1) as a white solid (64.3 mg, 57% yield). mp = 226–227 °C. 1H NMR (400 MHz, CDCl3) δ 10.20 (br s, 1H), 8.43 (d, J = 7.6 Hz, 1H), 8.30 (d, J = 8.4 Hz, 1H), 7.90 (br s, 1H), 7.88 (s, 1H), 7.68 (d, J = 8.0 Hz, 2H), 7.60 (d, J = 7.6 Hz, 2H), 7.57–7.39 (m, 9H), 7.12 (d, J = 8.4 Hz, 2H), 2.29 (s, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 167.0, 146.8, 145.1, 140.0, 138.2, 137.6, 135.1, 134.7, 133.6, 132.7, 132.2, 130.5, 130.0, 129.7, 129.0, 128.7, 128.1, 127.2, 126.9, 126.4, 125.9, 124.3, 123.8, 118.5, 117.7, 114.5, 108.2, 21.5 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C32H2335ClN2NaO4S+ 589.0959; Found 589.0967.

N-(4-Hydroxy-2-(3-nitrophenyl)-9-tosyl-9H-carbazol-3-yl)benzamide (3as)

Following the general procedure, 3as was prepared from 1a (63.3 mg, 0.2 mmol) and 2s (74.0 mg, 0.24 mmol) in 24 h. 3as was isolated by column chromatography (CH2Cl2/petroleum ether = 5:1) as a white solid (86.6 mg, 75% yield). mp = 257–258 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.35 (br s, 1H), 9.73 (br s, 1H), 8.37 (t, J = 1.8 Hz, 1H), 8.28–8.26 (m, 2H), 8.17 (dd, J = 1.4 Hz, 1H), 7.97 (d, J = 7.6 Hz, 1H), 7.81 (d, J = 8.4 Hz, 2H), 7.78–7.76 (m, 3H), 7.70 (t, J = 8.0 Hz, 1H), 7.58 (t, J = 8.4 Hz, 1H), 7.52–7.45 (m, 2H), 7.42 (t, J = 7.6 Hz, 2H) 7.34 (d, J = 8.4 Hz, 2H), 2.29 (s, 3H) ppm. 13C{1H} NMR (100 MHz, DMSO-d6) δ 166.9, 150.6, 147.4, 145.9, 141.3, 138.6, 137.4, 137.3, 135.7, 134.4, 133.6, 131.3, 130.3, 129.8, 128.0, 127.7, 127.1, 126.4, 125.1, 124.6, 123.5, 123.0, 122.2, 118.2, 114.6, 114.2, 106.2, 21.1 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C32H23N3NaO6S+ 600.1200; Found 600.1207.

N-(2-(2-Chlorophenyl)-4-hydroxy-9-tosyl-9H-carbazol-3-yl)benzamide (3at)

Following the general procedure, 3at was prepared from 1a (63.3 mg, 0.2 mmol) and 2t (71.4 mg, 0.24 mmol) in 24 h. 3at was isolated by column chromatography (CH2Cl2/petroleum ether = 1:1) as a white solid (22.6 mg, 20% yield). mp = 226–227 °C. 1H NMR (400 MHz, CDCl3) δ 10.24, 8.43 (d, J = 7.6 Hz, 1H), 8.31 (d, J = 8.4 Hz, 1H), 7.85 (s, 1H), 7.77 (br s, 1H), 7.68 (d, J = 8.4 Hz, 2H), 7.65–7.62 (m, 2H), 7.54–7.35 (m, 10H), 7.10 (d, J = 8.4 Hz, 2H), 2.27 ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 167.2, 146.4, 145.0, 138.2, 137.4, 136.9, 134.5, 133.9, 132.5, 132.5, 132.3, 132.1, 130.3, 130.0, 129.6, 128.9, 127.7, 127.1, 126.8, 126.5, 126.2, 124.3, 123.8, 119.3, 118.0, 114.6, 108.5, 21.5 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C32H23ClN2NaO4S+ 589.0959; Found 589.0970.

N-(4-Hydroxy-5-methyl-2-phenyl-9-tosyl-9H-carbazol-3-yl)benzamide (3ba)

Following the general procedure, 3ba was prepared from 1b (66.1 mg, 0.2 mmol) and 2a (63.2 mg, 0.24 mmol) at 60 °C in 24 h. 3ba was isolated by column chromatography (CH2Cl2/petroleum ether = 1:1) as a white solid (57.9 mg, 53% yield). mp = 214–215 °C. 1H NMR (400 MHz, CDCl3) δ 9.85 (br s, 1H), 8.25 (d, J = 8.0 Hz, 1H), 8.04 (s, 1H), 7.94 (br s, 1H), 7.63 (d, J = 8.4 Hz, 2H), 7.58–7.49 (m, 8H), 7.38 (t, J = 7.6 Hz, 2H), 7.35 (t, J = 7.8 Hz, 1H), 7.18 (d, J = 7.6 Hz, 1H), 7.11 (d, J = 8.0 Hz, 2H), 3.02, 2.28 ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 167.0, 145.9, 144.9, 139.1, 138.3, 138.1, 135.4, 134.7, 134.4, 132.5, 132.2, 129.7, 129.6, 129.2, 128.9, 128.5, 127.5, 127.2, 126.8, 126.5, 125.1, 119.6, 118.3, 112.3, 108.3, 25.1, 21.5 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C33H26N2NaO4S+ 569.1505; Found 569.1515.

N-(4-Hydroxy-6-methyl-2-phenyl-9-tosyl-9H-carbazol-3-yl)benzamide (3ca)

Following the general procedure, 3ca was prepared from 1c (66.1 mg, 0.2 mmol) and 2a (63.2 mg, 0.24 mmol) in 24 h. 3ca was isolated by column chromatography (CH2Cl2/petroleum ether = 1:1) as a white solid (100.5 mg, 92% yield). mp = 245–246 °C. 1H NMR (400 MHz, CDCl3) δ 10.34 (br s, 1H), 8.24 (s, 1H), 8.17 (d, J = 8.4 Hz, 1H), 7.98 (br s, 1H), 7.88 (s, 1H), 7.66 (d, J = 8.4 Hz, 2H), 7.60–7.50 (m, 8H), 7.42–7.38 (m, 2H), 7.29 (dd, J = 1.2, 8.8 Hz, 1H), 7.11 (d, J = 8.0 Hz, 2H), 2.51, 2.28 ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 166.7, 146.4, 144.8, 138.2, 137.8, 136.3, 134.9, 134.7, 133.9, 132.5, 132.3, 129.9, 129.6, 129.2, 128.9, 128.5, 127.9, 127.2, 126.4, 126.3, 123.8, 118.7, 117.4, 114.2, 108.3, 21.5, 21.4 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C33H26N2NaO4S+ 569.1505; Found 569.1508.

N-(7-Chloro-4-hydroxy-2-phenyl-9-tosyl-9H-carbazol-3-yl)benzamide (3da)

Following the general procedure, 3da was prepared from 1d (70.2 mg, 0.2 mmol) and 2a (63.2 mg, 0.24 mmol) in 24 h. 3da was isolated by column chromatography (CH2Cl2/petroleum ether = 1:1) as a white solid (48.5 mg, 43% yield). mp = 232–233 °C. 1H NMR (400 MHz, CDCl3) δ 10.42 (br s, 1H), 8.34–8.32 (m, 2H), 7.99 (br s, 1H), 7.85 (s, 1H), 7.69 (d, J = 8.4 Hz, 2H), 7.60–7.48 (m, 8H), 7.41–7.36 (m, 3H), 7.16 (d, J = 8.0 Hz, 2H), 2.31 ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 166.8, 146.4, 145.3, 138.6, 138.0, 137.6, 135.4, 134.5, 132.6, 132.5, 132.1, 129.8, 129.8, 129.3, 128.9, 128.7, 127.2, 126.5, 124.7, 124.6, 124.4, 118.9, 116.6, 114.7, 108.1, 21.5 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C32H2335ClN2NaO4S 589.0959; Found 589.0964.

N-(9-Acetyl-4-hydroxy-2-phenyl-9H-carbazol-3-yl)benzamide (3ea)

Following the general procedure, 3ea was prepared from 1e (40.8 mg, 0.2 mmol) and 2a (63.2 mg, 0.24 mmol) in 36 h. 3ea was isolated by column chromatography (CH2Cl2/petroleum ether = 1:1) as a white solid (26.1 mg, 31% yield). mp = 236–237 °C. 1H NMR (400 MHz, CDCl3) δ 10.48 (br s, 1H), 8.60 (d, J = 7.2 Hz, 1H), 8.10 (d, J = 8.4 Hz, 1H), 8.02 (br s, 1H), 7.87 (s, 1H), 7.56–7.44 (m, 10H), 7.40 (t, J = 7.8 Hz, 2H), 2.98 (s, 3H), 2.87 (s, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 170.1, 166.7, 146.4, 138.4, 138.2, 137.9, 134.9, 132.5, 132.4, 129.9, 129.2, 128.9, 128.5, 127.3, 126.5, 126.2, 123.9, 118.6, 116.9, 115.2, 109.8, 27.8 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C27H20N2NaO3+ 443.1366; Found 443.1369.

tert-Butyl 3-Benzamido-4-hydroxy-2-phenyl-9H-carbazole-9-carboxylate (3fa)

Following the general procedure, 3fa was prepared from 1f (52.5 mg, 0.2 mmol) and 2a (63.2 mg, 0.24 mmol) in 24 h. 3fa was isolated by column chromatography (CH2Cl2/petroleum ether = 1:1) as a white solid (63.2 mg, 66% yield). mp = 215–217 °C. 1H NMR (400 MHz, CDCl3) δ 10.37 (br s, 1H), 8.56 (d, J = 7.2 Hz, 1H), 8.23 (d, J = 8.0 Hz, 1H), 8.02 (br s, 1H), 7.95 (s, 1H), 7.57–7.36 (m, 12H), 1.74 (s, 9H) ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 166.6, 151.0, 146.3, 138.7, 138.1, 137.8, 134.7, 132.4, 132.3, 129.8, 129.0, 128.8, 128.2, 127.2, 126.3, 125.5, 123.5, 123.3, 117.8, 116.4, 115.5, 109.7, 84.0, 28.3 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C30H26N2NaO4+ 501.1785; Found 501.1789.

N-(1-Hydroxy-3-phenyldibenzo[b,d]thiophen-2-yl)benzamide (3ha)

Following the general procedure, 3ha was prepared from 1h (35.8 mg, 0.2 mmol) and 2a (63.2 mg, 0.24 mmol) at 60 °C in 36 h. 3ha was isolated by column chromatography (CH2Cl2/petroleum ether = 1:1) as a white solid (31.3 mg, 40% yield). mp = 225–226 °C. 1H NMR (400 MHz, CDCl3) δ 10.44 (br s, 1H), 8.94 (d, J = 8.0 Hz, 1H), 8.01 (br s, 1H), 7.84 (d, J = 7.2 Hz, 1H) 7.57–7.44 (m, 10H), 7.41–7.38 (m, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 166.9, 148.4, 139.0, 138.8, 137.9, 135.8, 134.8, 132.5, 132.4, 129.7, 129.2, 128.9, 128.5, 127.3, 126.5, 126.0, 124.6, 122.0, 119.4, 115.3 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C25H17NNaO2S+ 418.0872; Found 418.0878.

N-(4-Hydroxy-2-phenyldibenzo[b,d]thiophen-3-yl)benzamide (3ia)

Following the general procedure, 3ia was prepared from 1i (35.8 mg, 0.2 mmol) and 2a (63.2 mg, 0.24 mmol) using Cs2CO3 (130.3 mg, 0.4 mmol) as a base in 12 h. 3ia was isolated by column chromatography (CH2Cl2/petroleum ether = 1:1) as a white solid (23.5 mg, 30% yield). mp = 227–228 °C. 1H NMR (400 MHz, CDCl3) δ 10.49 (br s, 1H), 8.08–8.06 (m, 2H), 7.92–7.90 (m, 1H), 7.68 (s, 1H), 7.59–7.44 (m, 10H), 7.40 (t, J = 7.6 Hz, 2H) ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 166.6, 144.9, 140.4, 138.1, 135.6, 134.8, 133.4, 132.6, 132.4, 130.6, 129.9, 129.3, 128.9, 128.5, 127.3, 126.6, 124.4, 123.1, 121.7, 119.9, 114.6 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C25H17NNaO2S 418.0872; Found 418.0882.

N-(1-Hydroxy-3-phenyldibenzo[b,d]furan-2-yl)benzamide (3ja)

Following the general procedure, 3ja was prepared from 1j (32.6 mg, 0.2 mmol) and 2a (63.2 mg, 0.24 mmol) at 60 °C in 24 h. 3ja was isolated by column chromatography (CH2Cl2/petroleum ether = 1:1) as a white solid (46.6 mg, 61% yield). mp = 238–240 °C. 1H NMR (400 MHz, CDCl3) δ 10.26 (br s, 1H), 8.09 (br s, 1H), 7.90 (d, J = 7.2 Hz, 1H), 7.68 (d, J = 8.4 Hz, 1H), 7.59–7.46 (m, 10H), 7.40 (t, J = 7.8 Hz, 2H), 7.35 (t, J = 8.0 Hz, 1H) ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 166.7, 156.8, 146.8, 138.1, 136.7, 132.6, 132.2, 131.1, 129.9, 129.2, 128.9, 128.4, 127.3, 127.2, 124.1, 123.4, 122.9, 121.7, 120.6, 112.9, 112.1 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C25H17NNaO3+ 402.1101; Found 402.1102.

Procedure for the Synthesis of Compound 4

To a mixture of 3aa (106.5 mg, 0.2 mmol) and K2CO3 (41.4 mg, 0.3 mmol) in CH3CN (5 mL) was added CH3I (42.6 mg, 0.3 mmol, 19 μL) under a N2 atmosphere. The mixture was stirred at 30 °C (oil bath) for 12 h. After completion, the solvent was removed in vacuo, and H2O (10 mL) was added. The aqueous solution was extracted with CH2Cl2 (10 mL) three times. The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel (CH2Cl2/petroleum ether = 3:1) to give 4.

N-(4-Methoxy-2-phenyl-9-tosyl-9H-carbazol-3-yl)benzamide (4)

White solid. 108.5 mg, 99% yield. mp > 300 °C. 1H NMR (400 MHz, DMSO-d6) δ 9.89 (br s, 1H), 8.30 (d, J = 8.4 Hz, 1H), 8.16 (d, J = 7.6 Hz, 1H), 8.03 (s, 1H), 7.81 (t, J = 8.6 Hz, 4H), 7.63 (t, J = 8.4 Hz, 1H), 7.56–7.33 (m, 11H), 3.90 (s, 3H), 2.29 (s, 3H) ppm. 13C{1H} NMR (100 MHz, DMSO-d6) δ 166.7, 152.4, 146.0, 141.8, 139.2, 137.5, 137.4, 134.3, 133.6, 131.5, 130.4, 128.9, 128.4, 128.2, 127.8, 127.6, 127.4, 126.3, 124.9, 124.7, 123.8, 122.7, 118.3, 114.4, 110.9, 60.7, 21.1 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C33H26N2NaO4S+ 569.1505; Found 569.1517.

Procedure for the Synthesis of Compound 5

To a solution of 4 (109.3 mg, 0.2 mmol) in dry THF (5 mL) was added TBAF (1 M in THF, 1 mL). The solution was refluxed (oil bath) for 24 h. After cooling to room temperature, the solvent was removed in vacuo, and H2O (10 mL) was added. The aqueous solution was extracted with CH2Cl2 (10 mL) three times. The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel (EtOAc/petroleum ether = 1:1) to give 5.

N-(4-Methoxy-2-phenyl-9H-carbazol-3-yl)benzamide (5)

Canary solid. 70.7 mg, 90% yield. mp = 276–277 °C. 1H NMR (400 MHz, DMSO-d6) δ 11.47 (br s, 1H), 9.73 (br s, 1H), 8.14 (d, J = 7.6 Hz, 1H), 7.83 (d, J = 6.8 Hz, 2H), 7.56–7.41 (m, 7H), 7.37 (t, J = 7.6 Hz, 2H) 7.30–7.21 (m, 3H), 3.96 (s, 3H) ppm. 13C{1H} NMR (100 MHz, DMSO-d6) δ 167.0, 152.3, 140.2, 140.2, 140.1, 139.8, 134.9, 131.2, 128.9, 128.3, 127.9, 127.4, 126.9, 125.6, 122.0, 120.8, 119.2, 115.0, 111.0, 107.6, 60.3 ppm. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C26H20N2NaO2+ 415.1417; Found 415.1422.

Procedure for the Synthesis of Compound 6

To a solution of 3aa (53.3 mg, 0.1 mmol) in dioxane (3 mL) was added methanesulfonic acid (0.3 mmol, 28.8 mg). The solution was refluxed (oil bath) for 18 h. After cooling to room temperature, H2O (10 mL) was added. The aqueous solution was extracted with CH2Cl2 (10 mL) three times. The combined organic layers were dried over anhydrous MgSO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel (CH2Cl2/petroleum ether = 1:2) to give 6.

2,4-Diphenyl-6-tosyl-6H-oxazolo[4,5-c]carbazole (6)

White solid. 49.7 mg, 97% yield. mp = 270–272 °C. 1H NMR (400 MHz, CDCl3) δ 8.62 (s, 1H), 8.43 (d, J = 8.4 Hz, 1H), 8.37–8.35 (m, 2H), 8.26 (d, J = 7.6 Hz, 1H), 8.19 (d, J = 7.6 Hz, 2H), 7.73 (d, J = 8.4 Hz, 2H), 7.62–7.46 (m, 8H), 7.10 (d, J = 8.4 Hz, 2H), 2.24 (s, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3) δ 162.5, 145.1144.6, 138.8, 137.4, 137.0, 136.9, 134.7, 131.7, 131.3, 129.7, 129.4, 128.8, 128.7, 128.1, 127.6, 127.4, 127.1, 126.5, 124.5, 123.4, 122.1, 115.5, 110.7, 110.4, 21.5 ppm. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C32H23N2O3S+ 515.1424; Found 515.1434.

Procedure for the Synthesis of Compound 7

To a solution of 3aa (106.6 mg, 0.2 mmol) in dioxane (2 mL) was added hydrazine hydrate (85%, 1.0 mL). The mixture was stirred at 100 °C (oil bath) for 4 h. After cooling to room temperature, the pH of mixture was adjusted to 6 with aqueous HCl (1 M). The mixture was extracted with CH2Cl2 (10 mL) three times. The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was dissolved in anhydrous THF (4 mL), and 1,1′-carbonyldiimidazole (CDI) (0.24 mmol, 38.9 mg) was added. The solution was refluxed (oil bath) for 4 h. After cooling to room temperature, the solvent was removed in vacuo. The residue was purified by column chromatography on silica gel (CH2Cl2) to give 7.

4-Phenyl-3,6-dihydro-2H-oxazolo[4,5-c]carbazol-2-one (7)

White solid. 48.0 mg, 53% yield. mp > 300 °C. 1H NMR (400 MHz, DMSO-d6) δ 11.97 (br s, 1H), 8.29 (d, J = 8.4 Hz, 1H), 8.07 (s, 1H), 8.01 (d, J = 7.6 Hz, 1H), 7.76–7.51 (m, 9H), 7.30 (d, J = 7.6 Hz, 2H), 2.25 (s, 3H) ppm. 13C{1H} NMR (100 MHz, DMSO-d6) δ 154.9, 145.8, 138.1, 136.8, 136.2, 134.0, 133.3, 130.2, 129.2, 128.4, 128.3, 126.3, 125.0, 124.8, 123.6, 122.2, 114.9, 109.3, 109.0, 21.0 ppm. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C26H19N2O4S+ 455.1060; Found 455.1065.

Acknowledgments

We are grateful to the Natural Science Foundation of Zhejiang (nos. LQ20B020006 and LY18B020003), the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang (no. 2019R01005), Chemical Engineering & Technology of Zhejiang Province First-Class Discipline (Taizhou University), and the College Students’ Science and Technology Innovation Project of Zhejiang (2019R436017) for financial support.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.1c01992.

  • Single-crystal X-ray structures and copies of NMR spectra (PDF)

  • X-ray crystallographic data for compound 3aa (CIF)

The authors declare no competing financial interest.

Supplementary Material

ao1c01992_si_001.pdf (3.6MB, pdf)
ao1c01992_si_002.cif (234.2KB, cif)

References

  1. a Schmidt A. W.; Reddy K. R.; Knölker H.-J. Occurrence, biogenesis, and synthesis of biologically active carbazole alkaloids. Chem. Rev. 2012, 112, 3193–3328. 10.1021/cr200447s. [DOI] [PubMed] [Google Scholar]; b Roy J.; Jana A. K.; Mal D. Recent trends in the synthesis of carbazoles: an update. Tetrahedron 2012, 68, 6099–6121. 10.1016/j.tet.2012.05.007. [DOI] [Google Scholar]
  2. Sakano K. I.; Ishimaru K.; Nakamura S. New antibiotics, carbazomycins A and B. I. Fermentation, extraction, purification and physicochemical and biological properties. J. Antibiot. 1980, 33, 683–689. 10.7164/antibiotics.33.683. [DOI] [PubMed] [Google Scholar]
  3. O’Reilly M.; Kirkwood N. K.; Kenyon E. J.; Huckvale R.; Cantillon D. M.; Waddell S. J.; Ward S. E.; Richardson G. P.; Kros C. J.; Derudas M. Design, synthesis, and biological evaluation of a new series of carvedilol derivatives that protect sensory hair cells from aminoglycoside-induced damage by blocking the mechanoelectrical transducer channel. J. Med. Chem. 2019, 62, 5312–5329. 10.1021/acs.jmedchem.8b01325. [DOI] [PubMed] [Google Scholar]
  4. a Scott T. L.; Söderberg B. C. G. Palladium-catalyzed synthesis of 1, 2-dihydro-4(3H)-carbazolones. Formal total synthesis of murrayaquinone A. Tetrahedron 2003, 59, 6323–6332. 10.1016/S0040-4020(03)00976-1. [DOI] [Google Scholar]; b Sissouma D.; Maingot L.; Collet S.; Guingant A. Concise and efficient synthesis of calothrixin B. J. Org. Chem. 2006, 71, 8384–8389. 10.1021/jo061270o. [DOI] [PubMed] [Google Scholar]
  5. a Aggarwal T.; Sushmita; Verma A. K. Recent advances in the synthesis of carbazoles from indoles. Org. Biomol. Chem. 2019, 17, 8330–8342. 10.1039/C9OB01381D. [DOI] [PubMed] [Google Scholar]; b Banerjee A.; Kundu S.; Bhattacharyya A.; Sahu S.; Maji M. S. Benzannulation strategies for the synthesis of carbazoles, indolocarbazoles, benzocarbazoles, and carbolines. Org. Chem. Front. 2021, 8, 2710–2771. 10.1039/D1QO00092F. [DOI] [Google Scholar]
  6. Selected examples:; a Yuan Z.-G.; Wang Q.; Zheng A.; Zhang K.; Lu L.-Q.; Tang Z.; Xiao W.-J. Visible light-photocatalysed carbazole synthesis via a formal (4+2) cycloaddition of indole-derived bromides and alkynes. Chem. Commun. 2016, 52, 5128–5131. 10.1039/C5CC10542K. [DOI] [PubMed] [Google Scholar]; b Zhou T.; Li B.; Wang B. Rhodium-catalyzed C2 and C4 C–H activation/annulation of 3-(1H-indol-3-yl)-3-oxopropanenitriles with internal alkynes: a facile access to substituted and fused carbazoles. Chem. Commun. 2017, 53, 6343–6346. 10.1039/C7CC02808C. [DOI] [PubMed] [Google Scholar]; c Li Q.; Li B.; Wang B. Rhodium-catalyzed intramolecular cascade sequence for the formation of fused carbazole-annulated medium-sized rings by cleavage of C(sp2)–H/C(sp3)–H bonds. Chem. Commun. 2018, 54, 9147–9150. 10.1039/C8CC04428G. [DOI] [PubMed] [Google Scholar]; d Xiao Y.; Xiong H.; Sun S.; Yu J.; Cheng J. Rh(III)-Catalyzed dual C–H functionalization of 3-(1H-indol-3-yl)-3-oxopropanenitriles with sulfoxonium ylides or diazo compounds toward polysubstituted carbazoles. Org. Biomol. Chem. 2018, 16, 8715–8718. 10.1039/C8OB02145G. [DOI] [PubMed] [Google Scholar]; e Wang H.; Wang Z.; Wang Y.-L.; Zhou R.-R.; Wu G.-C.; Yin S.-Y.; Yan X.; Wang B. N-Bromosuccinimide (NBS)-catalyzed C-H bond functionalization: an annulation of alkynes with electron withdrawing group (EWG)-substituted acetyl indoles for the synthesis of carbazoles. Org. Lett. 2017, 19, 6140–6143. 10.1021/acs.orglett.7b03021. [DOI] [PubMed] [Google Scholar]
  7. Selected examples:; a Singh S.; Samineni R.; Pabbaraja S.; Mehta G. A general carbazole synthesis via stitching of indole-ynones with nitromethanes: application to total synthesis of carbazomycin A, calothrixin B, and staurosporinone. Org. Lett. 2019, 21, 3372–3376. 10.1021/acs.orglett.9b01111. [DOI] [PubMed] [Google Scholar]; b Kong L.; Wang M.; Wang Y.; Song B.; Yang Y.; Yao Q.; Li Y. Merging base-promoted C–C bond cleavage and iron-catalyzed skeletal rearrangement involving C–C/C–H bond activation: synthesis of highly functionalized carbazoles. Chem. Commun. 2018, 54, 11009–11012. 10.1039/C8CC06074F. [DOI] [PubMed] [Google Scholar]; c Yang Y.; Huang J.; Tan H.; Kong L.; Wang M.; Yuan Y.; Li Y. Synthesis of cyano-substituted carbazoles via successive C–C/C–H cleavage. Org. Biomol. Chem. 2019, 17, 958–965. 10.1039/C8OB03031F. [DOI] [PubMed] [Google Scholar]
  8. Ramalingam B. M.; Saravanan V.; Mohanakrishnan A. K. Synthesis of calothrixins and its analogs using FeCl3-mediated domino reaction protocol. Org. Lett. 2013, 15, 3726–3729. 10.1021/ol4015738. [DOI] [PubMed] [Google Scholar]
  9. a Kishbaugh T. L. S.; Gribble G. W. Diels–Alder reactions of 2- and 3-nitroindoles. A simple hydroxycarbazole synthesis. Tetrahedron Lett. 2001, 42, 4783–4785. 10.1016/S0040-4039(01)00854-1. [DOI] [Google Scholar]; b Andreini M.; De Paolis M.; Chataigner I. Thiourea-catalyzed dearomatizing [4+2] cycloadditions of 3-nitroindole. Catal. Commun. 2015, 63, 15–20. 10.1016/j.catcom.2014.07.042. [DOI] [Google Scholar]; c Yue D.-F.; Zhao J.-Q.; Chen X.-Z.; Zhou Y.; Zhang X.-M.; Xu X.-Y.; Yuan W.-C. Multiple Hydrogen-bonding bifunctional thiourea-catalyzed asymmetric dearomative [4 + 2] annulation of 3-nitroindoles: highly enantioselective access to hydrocarbazole skeletons. Org. Lett. 2017, 19, 4508–4511. 10.1021/acs.orglett.7b02068. [DOI] [PubMed] [Google Scholar]; d Pasturaud K.; Rkein B.; Sanselme M.; Sebban M.; Lakhdar S.; Durandetti M.; Legros J.; Chataigner I. The facile dearomatization of nitroaromatic compounds using lithium enolates of unsaturated ketones in conjugate additions and (4+2) formal cycloadditions. Chem. Commun. 2019, 55, 7494–7497. 10.1039/C9CC02924A. [DOI] [PubMed] [Google Scholar]; For reviews, see:; e Rkein B.; Bigot A.; Birbaum L.; Manneveau M.; De Paolis M.; Legros J.; Chataigner I. Reactivity of 3-nitroindoles with electron-rich species. Chem. Commun. 2021, 57, 27–44. 10.1039/D0CC06658C. [DOI] [PubMed] [Google Scholar]; f Cerveri A.; Bandini M. Recent advances in the catalytic functionalization of “electrophilic” indoles. Chin. J. Chem. 2020, 38, 287–294. 10.1002/cjoc.201900446. [DOI] [Google Scholar]
  10. a Pelkey E.; Gribble G. Synthesis and reactions of N-protected 3-nitroindoles. Synthesis 1999, 1999, 1117–1122. 10.1055/S-1999-3512. [DOI] [Google Scholar]; b Nowrouzi N.; Mehranpour A. M.; Bashiri E.; Shayan Z. Aromatic nitration under neutral conditions using N-bromosuccinimide/silver(I) nitrate. Tetrahedron Lett. 2012, 53, 4841–4842. 10.1016/j.tetlet.2012.06.126. [DOI] [Google Scholar]
  11. Gómez M. V.; Aranda A. I.; Moreno A.; Cossio F. P.; de Cozar A.; Diaz-Ortiz A.; de la Hoz A.; Prieto P. Microwave-assisted reactions of nitroheterocycles with dienes. Diels-Alder and tandem hetero Diels-Alder/[3,3] sigmatropic shift. Tetrahedron 2009, 65, 5328–5336. 10.1016/j.tet.2009.04.065. [DOI] [Google Scholar]
  12. Claudia D. D. R.; Carla M. O.; Ana S. S.; Maria N. K.; Luis R. D.; Pedro M. E. M. Polar Diels-Alder reactions developed in a protic ionic liquid: 3-nitroindole as dienophile. Theoretical studies using DFT methods. Lett. Org. Chem. 2012, 9, 691–695. 10.2174/157017812803901845. [DOI] [Google Scholar]
  13. Huang H.; Li Q.-Z.; Liu Y.-Q.; Leng H.-J.; Xiang P.; Dai Q.-S.; He X.-H.; Huang W.; Li J.-L. Dearomative [4 + 2] annulations between 3-nitroindoles and enals through oxidative N-heterocyclic carbene catalysis. Org. Chem. Front. 2020, 7, 3862–3867. 10.1039/D0QO00868K. [DOI] [Google Scholar]
  14. a Dell’Amico L.; Albrecht Ł.; Naicker T.; Poulsen P. H.; Jørgensen K. A. Beyond classical reactivity patterns: shifting from 1,4- to 1,6-additions in regio- and enantioselective organocatalyzed vinylogous reactions of olefinic lactones with enals and 2,4-dienals. J. Am. Chem. Soc. 2013, 135, 8063–8070. 10.1021/ja4029928. [DOI] [PubMed] [Google Scholar]; b Zhao S.; Zhao Y.-Y.; Lin J.-B.; Xie T.; Liang Y.-M.; Xu P.-F. Organocatalyzed asymmetric vinylogous allylic-allylic alkylation of Morita-Baylis-Hillman carbonates with olefinic azlactones: facile access to chiral multifunctional α-amino acid derivatives. Org. Lett. 2015, 17, 3206–3209. 10.1021/acs.orglett.5b01066. [DOI] [PubMed] [Google Scholar]
  15. a Gao T.-P.; Lin J.-B.; Hu X.-Q.; Xu P.-F. A catalytic asymmetric hetero-Diels-Alder reaction of olefinic azlactones and isatins: facile access to chiral spirooxindole dihydropyranones. Chem. Commun. 2014, 50, 8934–8936. 10.1039/C4CC03896G. [DOI] [PubMed] [Google Scholar]; b Gao T.-P.; Liu D.; Lin J.-B.; Hu X.-Q.; Wang Z.-Y.; Xu P.-F. Direct construction of chiral quaternary dihydropyranones through highly enantioselective organocatalytic hetero-Diels-Alder reactions of olefinic azlactones. Org. Chem. Front. 2016, 3, 598–602. 10.1039/C6QO00018E. [DOI] [Google Scholar]; c Zhu B.; Lu B.; Zhang H.; Xu X.; Jiang Z.; Chang J. Phase transfer-catalyzed, enantioselective vinylogous conjugate addition-cyclization of olefinic azlactones to access multifunctionalized chiral cyclohexenones. Org. Lett. 2019, 21, 3271–3275. 10.1021/acs.orglett.9b01001. [DOI] [PubMed] [Google Scholar]; d Joshi H.; Yadav A.; Das A.; Singh V. K. Organocatalytic asymmetric hetero-Diels-Alder reaction of in situ generated dienes: access to α, β-unsaturated δ-lactones featuring CF3-substituted quaternary stereocenter. J. Org. Chem. 2020, 85, 3202–3212. 10.1021/acs.joc.9b03076. [DOI] [PubMed] [Google Scholar]
  16. de Castro P. P.; Carpanez A. G.; Amarante G. W. Azlactone reaction developments. Chem.—Eur. J. 2016, 22, 10294–10318. 10.1002/chem.201600071. [DOI] [PubMed] [Google Scholar]
  17. Curti C.; Battistini L.; Sartori A.; Zanardi F. New developments of the principle of vinylogy as applied to π-extended enolate-type donor systems. Chem. Rev. 2020, 120, 2448–2612. 10.1021/acs.chemrev.9b00481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Cao D.; Ying A.; Mo H.; Chen D.; Chen G.; Wang Z.; Yang J. [4 + 2] annulation of 3-nitroindoles with alkylidene malononitriles: entry to substituted carbazol-4-amine derivatives. J. Org. Chem. 2018, 83, 12568–12574. 10.1021/acs.joc.8b01876. [DOI] [PubMed] [Google Scholar]
  19. The structure of the byproduct 3aa′ was established on the basis of spectroscopic data. In the 1H NMR of 3aa′, the two methyl protons resonated at δ 2.31 and 2.28 ppm. Moreover, 3aa′ gave a [M + Na]+ ion at m/z 709.1448 in the ESI-TOF HRMS appropriate for a molecular formula of C39H30N2O6S2 (calcd for C39H30N2O6NaS2+ 709.1437). For references on tosylation of phenols using N-tosyl reagents, see:; a Krishnan R. A.; Babu S. A.; Nitha P. R.; Krishnan J.; John J. Synthesis of benzothienobenzofurans via annulation of electrophilic benzothiophenes with phenols. Org. Lett. 2021, 23, 1814–1819. 10.1021/acs.orglett.1c00219. [DOI] [PubMed] [Google Scholar]; b Jones C. S.; Bull S. D.; Williams J. M. J. DBN hexafluorophosphate salts as convenient sulfonylating and phosphonylating agents. Org. Biomol. Chem. 2016, 14, 8452–8456. 10.1039/C6OB01854H. [DOI] [PubMed] [Google Scholar]; c Dhonthulachitty C.; Kothakapu S. R.; Neella C. K. An efficient practical tosylation of phenols, amines, and alcohols employing mild reagent [DMAPTs]+Cl–. Tetrahedron Lett. 2016, 57, 4620–4623. 10.1016/j.tetlet.2016.09.010. [DOI] [Google Scholar]
  20. CCDC 2068505 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures.
  21. The reaction of 2u and 1a was attempted under optimized conditions, and only trace amount of product was obtained maybe due to its steric hindrance. 2v also proved to be unreactive because of weak acidity.Inline graphic
  22. The reaction of 5-methoxy-3-nitrobenzofuran 1k and 2a under the optimized conditions gave complex byproducts.
  23. Li Y.; Tur F.; Nielsen R. P.; Jiang H.; Jensen F.; Jørgensen K. A. Enantioselective formal [4+2] cycloadditions to 3-nitroindoles by trienamine catalysis: synthesis of chiral dihydrocarbazoles. Angew. Chem., Int. Ed. 2016, 55, 1020–1024. 10.1002/anie.201509693. [DOI] [PubMed] [Google Scholar]
  24. Alayrac C.; Schollmeyer D.; Witulski B. First total synthesis of antiostatin A1, a potent carbazole-based naturally occurring antioxidant. Chem. Commun. 2009, 45, 1464–1466. 10.1039/B820291E. [DOI] [PubMed] [Google Scholar]
  25. Chan A. K. W.; Lam E. S. H.; Tam A. Y. Y.; Tsang D. P. K.; Lam W. H.; Chan M. Y.; Wong W. T.; Yam V. W. W. Synthesis and characterization of luminescent cyclometalated platinum(II) complexes of 1, 3-bis-hetero-azolylbenzenes with tunable color for applications in organic light-emitting devices through extension of π conjugation by variation of the heteroatom. Chem.-Eur. J. 2013, 19, 13910–13924. 10.1002/chem.201301586. [DOI] [PubMed] [Google Scholar]
  26. Kim H.; Kim B.; Kim Y.; Kim C.; Shin C.; Lee S.; Yu E.; Choi B.; Hwang K.. Condensed cyclic compounds and organic light-emitting devices including the same. EP 2894157 A1, 2015.
  27. Yang X.; Shan G.; Rao Y. Synthesis of 2-aminophenols and heterocycles by Ru-catalyzed C-H mono- and dihydroxylation. Org. Lett. 2013, 15, 2334–2337. 10.1021/ol400437a. [DOI] [PubMed] [Google Scholar]
  28. Sun C.-H.; Lu Y.; Zhang Q.; Lu R.; Bao L.-Q.; Shen M.-H.; Xu H.-D. Selective S-arylation of 2-oxazolidinethiones and selective N-arylation of 2-benzoxazolinones/2-benzimidazolinones. Org. Biomol. Chem. 2017, 15, 4058–4063. 10.1039/C7OB00040E. [DOI] [PubMed] [Google Scholar]
  29. Gurova K.; Wade W.. Compounds and methods for treating cancers. WO 2014153055 A2, 2014.
  30. Cheng Q.; Zhang H.-J.; Yue W.-J.; You S.-L. Palladium-catalyzed highly stereoselective dearomative [3 + 2] cycloaddition of nitrobenzofurans. Chem 2017, 3, 428–436. 10.1016/j.chempr.2017.06.015. [DOI] [Google Scholar]
  31. Lu S.-C.; Zheng P.-R.; Liu G. Iodine(III)-mediated tandem oxidative cyclization for construction of 2-nitrobenzo[b]furans. J. Org. Chem. 2012, 77, 7711–7717. 10.1021/jo301162x. [DOI] [PubMed] [Google Scholar]
  32. Chatterjee S.; Karuso P. An efficient and concise method to synthesize locked GFP chromophore analogues. Tetrahedron Lett. 2016, 57, 5197–5200. 10.1016/j.tetlet.2016.10.021. [DOI] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

ao1c01992_si_001.pdf (3.6MB, pdf)
ao1c01992_si_002.cif (234.2KB, cif)

Articles from ACS Omega are provided here courtesy of American Chemical Society

RESOURCES