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Article

Pd/Ag-Cocatalyzed Merging Intramolecular Oxidative Coupling and Cascade [4 + 2] Cycloaddition: Synthesis and Photophysical Properties of Novel Polycyclic N-Heterocycles Fused Naphthoquinones

by
Yu Dong
1,
Lin Chen
1,
Han-Qing Wu
1,
Li Xie
2,
Jing-Hao Yu
1,
Fan Yang
1,
Yu-Ting Wang
1,
Yu-Rong Liu
1,
Guo-Wei Deng
1,* and
Zhi-Fan Wang
1,*
1
Sichuan Provincial Key Laboratory for Structural Optimization and Application of Functional Molecules, College of Chemistry and Life Science, Chengdu Normal University, Chengdu 611130, China
2
Chengdu Institute for Drug Control, Chengdu 610061, China
*
Authors to whom correspondence should be addressed.
Molecules 2024, 29(23), 5639; https://doi.org/10.3390/molecules29235639
Submission received: 27 October 2024 / Revised: 24 November 2024 / Accepted: 25 November 2024 / Published: 28 November 2024
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Abstract

:
We report a step-economic strategy for the direct synthesis of novel polycyclic N-heterocycle-fused naphthoquinones by merging intramolecular oxidative coupling and cascade [4 + 2] cycloaddition. In the protocol, mechanistic investigations suggest that the cascade reaction involves the intermediate spiro polycyclic N-heterocycles and [4 + 2] cycloaddition processes. This protocol is featured with moderate to excellent yields, wide substrate scope, and divergent structures of products. In addition, the photophysical properties of the synthesized products were evaluated. These products exhibit interesting fluorescence properties, and surprisingly, the compounds have the ability to selectively recognize trifluoroacetic acid.

1. Introduction

N-Heterocycle-fused polycyclic organic scaffolds are privileged structural motifs that frequently occur in various, drugs, natural products, and functional materials [1,2,3,4,5,6,7]. The representative examples of the quinone-fused polycyclic N-heterocycles Calothrixin A and B both inhibited the in vitro growth of the chloroquine-resistant strain of the human parasite, Plasmodium falciparum, in a dose-dependent manner [8,9]. In addition, staurosporine (kinase inhibitor) [10], a potential candidate for cancer treatment [11], and midostaurin (FDA-approved drugs) were approved as drugs to treat patients diagnosed with a form of blood cancer known as acute myeloid leukemia in 2017 (Figure 1) [12,13]. In addition, some polycyclic compounds containing the basic structure, which are complex molecules, are privileged scaffolds that possess diverse applications in organic electronics [14,15] and a wide range of biological activities [16,17,18,19].
Annellated polycyclic complexes bearing a quinone skeleton are very promising for applications in various areas [20,21,22,23]. However, there are a few related reports on the construction of quinone-fused polycyclic N-heterocycles. The D–A addition reaction is one of the efficient strategies for constructing cyclized derivatives from naphthoquinones. For instance, in 1990, the Pindur group reported the first structural example of indolocarbazole-fused naphthoquinone by a Diels–Alder reaction of naphthoquinones and 3-vinylindole in only 10% yield [24]. In 2019, Fu’s group developed a formal [4 + 2] annulation of 2-methyl-3-oxoacetate indoles with naphthalene-1,4-dione [25]. In 2021, Wang’s research groups published B(C6F5)3-catalyzed three-component tandem reaction of naphthoquinone, indole, and maleimide [26]. In addition, the cycloaddition reaction is one of the effective methods for building complex cyclic structures from substituted naphthoquinones. For instance, in 2010, Zhang’s group reported a strategy to synthesize anthraquinone from bromoquinone and arylpropanoic acid [27]. In 2019, Albrecht’s group reported a [6 + 4]-cycloaddition reaction of 2-substituted 1,4-naphthoquinones with 8,8-dicyanoheptafulvene [28]. The cycloaddition reaction is also a classic strategy from indolenaphthoquinones. For instance, in 2020, Wang’s research groups realized the Co(II)-catalyzed cyclization reaction of indolequinones and aniline [29]. In 2023, they also reported the B(C6F5)3-catalyzed [4 + 2] cyclization/oxidative reaction of indolequinones and dimethyl butynedioates [30]. Despite their merits, many existing synthetic approaches have several shortcomings, such as the preparation of the prerequisite functional groups, multiple reaction steps, harsh reaction conditions, expensive catalysts, and low product yields.
In order to develop better methods, we have developed a strategy for the synthesis of polycyclic N-heterocycle- and indolecarbazole-fused naphthoquinones by merging oxidative coupling and cascade palladium-catalyzed intramolecular oxidative cyclization from bi-indolylnaphthoquinones (Scheme 1a) [31]. Herein, we report a step-economic strategy for the direct synthesis of novel polycyclic N-heterocycle-fused naphthoquinones by merging intramolecular oxidative coupling and cascade [4 + 2] cycloaddition. In the protocol, mechanistic investigations suggest that the cascade reaction involves the intermediate spiro polycyclic N-heterocycles and [4 + 2] cycloaddition processes (Scheme 1b).

2. Results

2.1. Synthesis

We commenced our investigation of oxidative coupling using bi-indolnaphthoquinone 1a and maleimide 2a as model substrates with the aim of obtaining the novel polycyclic N-heterocycle 3aa (Table 1). Next, we proceeded to investigate if the merging intramolecular oxidative coupling and cascade [4 + 2] cycloaddition process of bi-indolnaphthoquinones gave the intermediate spiro polycyclic N-heterocycle and maleimide 2a (Table 1). Other palladium catalysts were less effective than Pd(OTf)2 (entry 2; Supplementary Materials). Moreover, other catalysts and other oxidants were less effective than AgOAc and K2S2O8, respectively (entries 3 and 4; Supplementary Materials). Changing their composition led to low yields of 3aa (entry 5; Supplementary Materials), suggesting that the additives create suitable conditions for the cascade [4 + 2] cycloaddition. Switching the solvent and decreasing the reaction temperature was also ineffective in improving the yield of 3aa (entries 6–7; Supplementary Materials). After rigorous optimization studies, we found the initial conditions to be optimal (Table 1, entry 1), providing the product 3aa in 82% yield.
With the optimized conditions in hand, now, the scope of merging intramolecular oxidative coupling and cascade [4 + 2] cycloaddition process was explored, and the results are summarized in Table 2. First, we examined the scope of maleimides 2 by using 1a as the partner. Various N-alkyl-substituted maleimides such as –Me (2a), –Et (2b), –Pr(2c), –nBu (2d), –iBu (2e), –tBu (2f), n-pentyl (2g), n-hexyl (2h), cyclopropyl (2i), cyclopentyl (2j), and cyclohenxyl (2k) all reacted smoothly with bi-indolnaphthoquinone 1a to provide their corresponding polycyclic N-heterocycle products (3aa–3ak) in good yields (53–82%). The structure of 3ae was determined using single-crystal X-ray diffraction analysis (Table 2). N-unsubstituted maleimides (2l) successfully provided the desired product 3al (63%). Similarly, substituted N-benzylmaleimide (2m-2u) and ethylbenzene (2v) reacted well under this protocol to deliver the corresponding products 3am-3av, respectively, in good yields (57–81%). Further, maleimides derived from 2-ethoxyethyl amine (2w), thiophenemethyl amine (2x), thiophenethyl amine (2y), and 5-aminoindole (2z) all successfully gave their polycyclic N-heterocycle products 3aw–3az (in 53–79% yields).
Next, the merging intramolecular oxidative coupling and the cascade [4 + 2] cycloaddition reaction of bi-indolnaphthoquinone 1 that gave the intermediate spiro polycyclic N-heterocycle and maleimide 2 was investigated, and the results are listed in Table 3. N-alkyl-substituted indoles, such as Et, readily underwent the cascade [4 + 2] reaction to product 4a in yields of 78%. The reaction was compatible with a variety of indole moieties bearing electron-donating and electron-withdrawing substituents to produce the desired polycyclic N-heterocycle products (4b–4n) in moderate to good yields (52–78%). The structure of the polycyclic N-heterocycle 4i was confirmed by X-ray analysis. To our delight, the reaction also showed good compatibility with a wide range of valuable functional groups such as fluoro (4c and 4m), chloro (4d, 4f, and 4n), and bromo (4g). Tolerance to the halogen atoms was noteworthy since they have been frequently used for further modification. Moreover, we were pleased to find that the position of the substituent on the indole moiety showed no obvious influence on the reaction outcome, and substitutions at the C5, C6, or C7 were all well tolerated in the cascade [4 + 2] cycloaddition reaction.
The theoretical calculation part was completed by the Beijing density function (BDF) program (2024A) (Figure S1 in Supplementary Materials) [32]. The studies demonstrated the importance of K2S2O8 and Pd(OTf)2. Under the conditions of AgOAc and HOAc, the reaction of cyclization product intermediate 5 and 2a generated the polycyclic N-heterocycle product 3aa in a yield of 81% (Scheme 2, (d)). We surmised that the cyclization product 5 should be a key intermediate in this reaction. In the absence of AgOAc or HOAc, the reaction of compound 5 and 2a generated the polycyclic N-heterocycle product 3aa in just 69%, 66%, and 38% yield (Scheme 2, (e–g)). The studies demonstrated the importance of AgOAc and HOAc. A control experiment involved using AgOAc without Pd for substrates 1a and 2a, and the reaction of the polycyclic N-heterocycle product 3aa in a yield of 43% (Scheme 2, (h)). The studies demonstrated the importance of AgOAc and Pd(OTf)2.
On the basis of literature precedents and control experiments, a plausible mechanism is proposed in Scheme 3 [25,26,31,33,34,35]. Initially, the attack of the OH+ ion of (NH4)2S2O8 onto the nucleophilic center C-3 of indole (1a) generates enol intermediate (C) in situ through the intermediate compounds A and B. Palladium-catalyzed intramolecular nucleophilic attack of enol intermediate C form hydroquinone intermediate D. Then, the hydroquinone intermediate D further oxidized to spiro-cyclized polycyclic N-heterocycle products (5) by (NH4)2S2O8. At the same time, N-methylmaleimide (2a) is activated by AgOAc and HOAc, making intermediate E undergo the cascade [4 + 2] cycloaddition reaction with intermediate 5 to produce the final product 3aa.

2.2. Photophysical Properties

During the experiment, we found that the series of compounds showed an interesting photophysical phenomenon under 365 nm UV (Figure 2), so the photophysical properties of these compounds were characterized in the works (Figure 2, ESI Table S7 and Figures S2–S8). After comparing the fluorescence emission spectra of all products in ethyl acetate (EA) at a low concentration (3 × 10−5 M) (ESI Table S7, Figures S6 and S7), some interesting results were delivered. They emit between 565 and 662 nm in EA with moderate to good quantum yields (ranging from 0.10 to 0.83). The results indicated that the change of the functional groups on the indole-naphthoquinone skeletons had a greater impact on the relative quantum yield (ΦF) of compounds, while the change of the N-substituents of the maleimide had no significant impact on the photophysical properties of the compounds. Overall, these compounds had excellent relative fluorescence quantum yields, which provided them the potential for becoming fluorescent probes or chromogenic chemosensors.
To examine the selectivity, a fluorescence screening of various acids was carried out (Figure 3). Hence, 3aa as the model compound (3.0 × 10−5 M) in dichloromethane (DCM) interacted with 1000 equiv of different acids such as H3PO4, H2SO4, HCl, HNO3, TFA, benzoic acid, oxalic acid, HAc, phenylboronic acid, and benzenesulfonic acid. While strong emission enhancement was observed for the majority of the acids tested, surprisingly, nearly no fluorescence was observed due to fluorescence quenching with the TFA added into the solution, confirming its suitability for the selective sensing of TFA (Figure 4). Furthermore, using this, one can detect TFA selectively as it changes to a distinctly different color (red to purple) (Figure 3). The quantitative analysis was carried out by fluorescence spectral titration of 3aa with varying concentrations of TFA (0–1000 equiv) in DCM (Figure S8; Supplementary Materials). The colorimetric sensors are even better, as the signaling event can be detected by the naked eye itself.

3. Materials and Methods

Chemicals and analytical-grade solvents were purchased from commercial suppliers and used without further purification unless otherwise stated. All reagents were weighed and handled in air at room temperature. Analytical thin-layer chromatography was performed on glass plates of silica gel GF–254 with detection by UV light (254 and 365 nm). Column chromatography was carried out on silica gel (200–300 mesh). 1H NMR spectra were recorded at 400 MHz and 13C NMR spectra were recorded at 101 MHz by using Agilent 400 MHz NMR spectrometer (Swiss Bruker Company, Fällanden, Switzerland). Chemical shifts were calibrated using residual undeuterated solvent as an internal reference (1H NMR: CDCl3 7.26 ppm, DMSO-d6 2.50 ppm, 13C NMR: CDCl3 77.16 ppm, DMSO-d6 39.52 ppm). Data were reported as follows: chemical shift, multiplicity (s = singlet, br s = broad singlet, d = doublet, t = triplet, q = quartet, m = multiplet). Coupling constants (J) were reported in Hertz (Hz). Melting points were measured with a micro melting point apparatus. HRESIMS spectra were acquired using the waters G2-Xs qtof mass spectrometer (Waters, Milford, MA, USA). Single-crystal X-ray diffraction data were collected using a Bruker D8 Quest diffractometer (Swiss Bruker Company, Fällanden, Switzerland). (Mo Kα, λ = 0.71073 Å). Photophysical properties were evaluated on a Unic 4802 UV-Vis Double Beam spectrophotometer and a Horiba (Dual-fl) fluorescence spectrophotometer (Swiss Bruker Company, Fällanden, Switzerland).
To a solution of bi-indolnaphthoquinone 1 (0.1 mmol) and Pd(OTf)2 (0.03 mmol), AgOAc (0.03 mmol), K2S2O8 (0.2 mmol), and HOAc (0.3 mmol) in CH3CN (2 mL) was added maleimide 2. The reaction mixture was stirred at 100 °C under a sealed tube for 1 h. After the completion of the reaction (monitored by TLC), the reaction was quenched with saturated salt water (6 mL), and the mixture was extracted with EtOAc (3 × 3 mL). The organic extracts were washed with brine, dried over Na2SO4, filtered, and the solvent was removed in vacuo. The crude product was purified by silica gel column chromatography to give 3 or 4.
1,5′,7′-trimethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (3aa): A pink solid (44 mg, 82% yield); mp 293–295 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.53 (d, J = 7.7 Hz, 1H), 8.26 (d, J = 7.7 Hz, 1H), 7.99 (d, J = 7.8 Hz, 1H), 7.77 (t, J = 7.5 Hz, 1H), 7.65 (t, J = 7.5 Hz, 1H), 7.45 (t, J = 7.8 Hz, 1H), 7.11 (t, J = 7.7 Hz, 1H), 6.96 (d, J = 7.5 Hz, 1H), 6.74 (d, J = 7.8 Hz, 1H), 6.67 (d, J = 9.0 Hz, 2H), 6.54 (t, J = 7.7 Hz, 1H), 4.89 (d, J = 8.0 Hz, 1H), 4.65 (d, J = 8.0 Hz, 1H), 3.34 (s, 3H), 3.01 (s, 3H), 2.71 (s, 3H). 13CNMR (101 MHz, CDCl3) δ 193.23, 178.41, 174.81, 173.66, 171.54, 162.62, 160.85, 143.80, 137.22, 136.75, 135.03, 134.79, 133.30, 129.86, 128.68, 127.52, 127.38, 124.41, 122.82, 121.85, 120.04, 119.77, 118.94, 108.88, 108.47, 85.69, 80.44, 69.23, 47.58, 41.17, 30.80, 26.60, 24.61. HRMS (ESI) m/z calcd for C33H23N3O5Na+(M + Na)+ 564.1533, found 564.1535.
7′-ethyl-1,5′-dimethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (3ab): A pink solid (41 mg, 74% yield); mp 274–276 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.51 (d, J = 7.7 Hz, 1H), 8.27 (d, J = 7.4 Hz, 1H), 8.00 (d, J = 7.4 Hz, 1H), 7.77 (t, J = 7.1 Hz, 1H), 7.65 (t, J = 7.1 Hz, 1H), 7.46 (t, J = 7.3 Hz, 1H), 7.11 (t, J = 7.4 Hz, 1H), 6.95 (t, J = 7.5 Hz, 1H), 6.78–6.66 (m, 3H), 6.55 (t, J = 7.5 Hz, 1H), 4.85 (d, J = 7.9 Hz, 1H), 4.60 (d, J = 7.9 Hz, 1H), 3.34 (s, 3H), 3.30–3.21 (m, 2H), 3.02 (s, 3H), 0.86 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz CDCl3) δ 193.33, 178.23, 174.62, 173.50, 171.49, 162.77, 160.77, 143.82, 137.24, 136.71, 135.01, 134.91, 133.28, 129.84, 128.53, 127.46, 127.37, 124.46, 122.78, 121.94, 120.10, 119.76, 119.01, 108.94, 108.45, 86.01, 80.07, 69.44, 47.45, 41.01, 33.64, 30.86, 26.59, 12.75. HRMS (ESI) m/z calcd for C34H25N3O5Na+ (M + Na)+ 578.1683, found 578.1692.
1,5′-dimethyl-7′-propyl-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (3ac): A pink solid (40 mg, 70% yield); mp 289–291 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.52 (d, J = 7.7 Hz, 1H), 8.27 (d, J = 7.8 Hz, 1H), 7.99 (d, J = 7.7 Hz, 1H), 7.77 (t, J = 7.4 Hz, 1H), 7.64 (t, J = 7.5 Hz, 1H), 7.45 (t, J = 7.7 Hz, 1H), 7.11 (t, J = 7.7 Hz, 1H), 6.94 (t, J = 7.5 Hz, 1H), 6.77–6.65 (m, 3H), 6.55 (t, J = 7.7 Hz, 1H), 4.86 (d, J = 8.0 Hz, 1H), 4.61 (d, J = 8.0 Hz, 1H), 3.34 (s, 3H), 3.15 (t, J = 7.4 Hz, 2H), 3.01 (s, 3H), 1.26 (sextet, J = 7.0 Hz, 2H), 0.74 (t, J = 7.4 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 193.45, 178.22, 174.79, 173.72, 171.47, 162.71, 160.93, 143.81, 137.24, 136.71, 135.02, 134.88, 133.27, 129.84, 128.63, 127.48, 127.35, 124.45, 122.79, 121.94, 120.16, 119.74, 119.02, 108.91, 108.45, 85.87, 80.51, 69.31, 47.47, 41.00, 40.50, 30.84, 26.60, 20.81, 11.27. HRMS (ESI) m/z calcd for C35H27N3O5Na+ (M + Na)+ 592.1854, found 592.1848.
7′-butyl-1,5′-dimethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (3ad): A pink solid (42 mg, 72% yield); mp 299–301 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.52 (d, J = 7.8 Hz, 1H), 8.27 (d, J = 7.8 Hz, 1H), 7.99 (d, J = 7.7 Hz, 1H), 7.76 (t, J = 7.5 Hz, 1H), 7.64 (t, J = 7.5 Hz, 1H), 7.45 (t, J = 7.8 Hz, 1H), 7.11 (t, J = 7.7 Hz, 1H), 6.94 (t, J = 7.5 Hz, 1H), 6.71 (dd, J = 7.6, 7.1 Hz, 3H), 6.55 (t, J = 7.6 Hz, 1H), 4.86 (d, J = 8.0 Hz, 1H), 4.61 (d, J = 8.0 Hz, 1H), 3.33 (s, 3H), 3.19 (t, J = 5.9 Hz, 2H), 3.01 (s, 3H), 1.23–1.05 (m, 4H), 0.84 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 188.66, 173.40, 170.04, 169.01, 166.71, 157.93, 156.09, 139.05, 132.53, 131.96, 130.27, 130.11, 128.50, 125.08, 123.90, 122.72, 122.59, 119.70, 118.05, 117.20, 115.59, 114.92, 114.28, 104.18, 103.70, 81.12, 76.17, 64.55, 42.73, 36.25, 33.93, 28.94, 26.11, 24.62, 21.85, 14.53. HRMS (ESI) m/z calcd for C36H29N3O5Na+ (M + Na)+ 606.2010, found 606.2005.
7′-isobutyl-1,5′-dimethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (3ae): A pink solid (36 mg, 61% yield); mp 252–254 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.52 (d, J = 7.8 Hz, 1H), 8.26 (d, J = 7.8 Hz, 1H), 7.99 (d, J = 7.7 Hz, 1H), 7.76 (t, J = 7.5 Hz, 1H), 7.64 (t, J = 7.5 Hz, 1H), 7.44 (t, J = 7.7 Hz, 1H), 7.11 (t, J = 7.7 Hz, 1H), 6.93 (t, J = 7.5 Hz, 1H), 6.78–6.62 (m, 3H), 6.54 (t, J = 7.7 Hz, 1H), 4.89 (d, J = 8.2 Hz, 1H), 4.64 (d, J = 8.2 Hz, 1H), 3.34 (s, 3H), 3.03 (d, J = 11.1 Hz, 5H), 1.67 (dt, J = 20.6, 6.9 Hz, 1H), 0.70 (dd, J = 19.0, 6.7 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 193.22, 178.24, 175.05, 174.00, 171.42, 162.63, 161.00, 143.80, 137.26, 136.74, 135.03, 134.84, 133.28, 129.84, 128.85, 127.48, 127.32, 124.44, 122.81, 121.93, 120.46, 119.67, 119.04, 108.90, 108.44, 85.70, 80.87, 69.17, 47.42, 46.47, 41.00, 30.81, 27.01, 26.61, 20.08, 20.05. HRMS (ESI) m/z calcd for C36H29N3O5Na+ (M + Na)+ 606.2010, found 606.2005.
7′-(tert-butyl)-1,5′-dimethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (3af): A pink solid (38 mg, 65% yield); mp 291–293 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.55 (d, J = 7.8 Hz, 1H), 8.27 (d, J = 7.9 Hz, 1H), 7.98 (d, J = 7.7 Hz, 1H), 7.76 (t, J = 7.5 Hz, 1H), 7.64 (t, J = 7.6 Hz, 1H), 7.46 (t, J = 7.8 Hz, 1H), 7.10 (t, J = 7.7 Hz, 1H), 6.95 (t, J = 7.5 Hz, 1H), 6.75–6.66 (m, 3H), 6.54 (t, J = 7.7 Hiiz, 1H), 4.70 (d, J = 8.3 Hz, 1H), 4.49 (d, J = 8.3 Hz, 1H), 3.33 (s, 3H), 3.00 (s, 3H), 1.28 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 193.44, 178.44, 176.11, 175.00, 171.47, 162.85, 160.84, 143.84, 137.24, 136.61, 135.06, 134.91, 133.57, 133.30, 129.76, 128.48, 127.34, 127.24, 124.45, 122.71, 122.01, 120.30, 119.60, 119.16, 108.87, 108.40, 86.34, 80.18, 69.74, 58.90, 47.49, 40.57, 30.83, 28.64, 28.04, 26.58. HRMS (ESI) m/z calcd for C36H29N3O5Na+ (M + Na)+ 606.2012, found 606.2005.
1,5′-dimethyl-7′-pentyl-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (3ag): A pink solid (32 mg, 54% yield); mp 242–244 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.52 (d, J = 7.7 Hz, 1H), 8.27 (d, J = 7.8 Hz, 1H), 7.99 (d, J = 7.6 Hz, 1H), 7.77 (t, J = 7.4 Hz, 1H), 7.64 (t, J = 7.5 Hz, 1H), 7.45 (t, J = 7.6 Hz, 1H), 7.11 (t, J = 7.7 Hz, 1H), 6.94 (t, J = 7.5 Hz, 1H), 6.71 (dd, J = 25.7, 6.9 Hz, 3H), 6.55 (t, J = 7.7 Hz, 1H), 4.86 (d, J = 8.0 Hz, 1H), 4.61 (d, J = 8.0 Hz, 1H), 3.34 (s, 3H), 3.18 (td, J = 7.5, 3.2 Hz, 2H), 3.01 (s, 3H), 1.25 (d, J = 6.2 Hz, 4H), 1.08 (q, J = 7.5 Hz, 2H), 0.84 (t, J = 7.3 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 193.33, 178.14, 174.78, 173.73, 171.47, 162.69, 160.81, 143.81, 137.29, 136.68, 135.01, 134.88, 133.24, 129.82, 128.65, 127.47, 127.33, 124.45, 122.80, 121.96, 120.29, 119.69, 119.03, 108.92, 108.45, 85.88, 80.02, 69.33, 47.47, 41.00, 38.86, 30.86, 29.68, 28.71, 27.22, 26.60, 22.14, 13.73. HRMS (ESI) m/z calcd for C37H31N3O5Na+ (M + Na)+ 620.2168, found 620.2161.
7′-hexyl-1,5′-dimethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (3ah): A pink solid (32 mg, 53% yield); mp 331–333 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.51 (d, J = 7.8 Hz, 1H), 8.27 (d, J = 7.8 Hz, 1H), 7.99 (d, J = 7.7 Hz, 1H), 7.77 (t, J = 7.4 Hz, 1H), 7.64 (t, J = 7.4 Hz, 1H), 7.45 (t, J = 7.6 Hz, 1H), 7.11 (t, J = 7.6 Hz, 1H), 6.94 (t, J = 7.5 Hz, 1H), 6.71 (dd, J = 26.3, 7.7 Hz, 3H), 6.55 (t, J = 7.6 Hz, 1H), 4.86 (d, J = 7.9 Hz, 1H), 4.60 (d, J = 7.9 Hz, 1H), 3.34 (s, 3H), 3.18 (s, 2H), 3.01 (s, 3H), 1.59 (s, 2H), 1.17 (dd, J = 40.6, 6.0 Hz, 6H), 0.86 (t, J = 6.7 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 193.21, 178.14, 174.77, 173.46, 171.47, 162.59, 160.61, 143.81, 137.28, 136.69, 135.01, 134.77, 133.24, 129.82, 128.64, 127.48, 127.34, 124.45, 122.80, 121.94, 120.28, 119.69, 119.03, 108.92, 108.45, 85.83, 80.43, 69.22, 47.48, 40.99, 38.87, 31.22, 30.86, 27.48, 26.60, 26.33, 22.31, 14.02. HRMS (ESI) m/z calcd for C38H33N3O5Na+ (M + Na)+ 634.2322, found 634.2318.
7′-cyclopropyl-1,5′-dimethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (3ai): A pink solid (34 mg, 60% yield); mp 273–275 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.51 (d, J = 7.7 Hz, 1H), 8.28 (d, J = 7.7 Hz, 1H), 7.99 (d, J = 7.7 Hz, 1H), 7.77 (t, J = 7.5 Hz, 1H), 7.65 (t, J = 7.5 Hz, 1H), 7.46 (t, J = 7.7 Hz, 1H), 7.11 (t, J = 7.7 Hz, 1H), 6.96 (t, J = 7.4 Hz, 1H), 6.77–6.65 (m, 3H), 6.54 (t, J = 7.6 Hz, 1H), 4.81 (d, J = 8.0 Hz, 1H), 4.56 (d, J = 8.0 Hz, 1H), 3.33 (s, 3H), 3.00 (s, 3H), 2.24 (dd, J = 11.4, 7.7 Hz, 1H), 0.81–0.65 (m, 2H), 0.55 (dd, J = 10.2, 5.3 Hz, 1H), 0.42–0.33 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 193.10, 178.42, 175.30, 174.12, 171.27, 162.65, 160.58, 143.80, 137.10, 136.84, 135.05, 134.90, 133.35, 129.85, 128.32, 127.48, 127.38, 124.42, 122.76, 121.90, 119.99, 119.85, 118.77, 109.04, 108.46, 86.12, 79.72, 69.26, 47.09, 40.54, 30.85, 26.60, 21.50, 5.14. HRMS (ESI) m/z calcd for C35H25N3O5Na+ (M + Na)+ 590.1694, found 590.1692.
7′-cyclopentyl-1,5′-dimethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (3aj): A pink solid (37 mg, 65% yield); mp 205–207 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.52 (d, J = 7.8 Hz, 1H), 8.27 (d, J = 7.8 Hz, 1H), 7.99 (d, J = 7.7 Hz, 1H), 7.77 (t, J = 7.4 Hz, 1H), 7.65 (t, J = 7.5 Hz, 1H), 7.46 (t, J = 7.7 Hz, 1H), 7.11 (t, J = 7.7 Hz, 1H), 6.95 (t, J = 7.5 Hz, 1H), 6.76–6.66 (m, 3H), 6.54 (t, J = 7.7 Hz, 1H), 4.80 (d, J = 8.0 Hz, 1H), 4.56 (d, J = 8.0 Hz, 1H), 4.15–4.08 (m, 1H), 3.33 (s, 3H), 3.01 (s, 3H), 1.79–1.57 (m, 8H). 13C NMR (101 MHz, CDCl3) δ 193.08, 178.08, 175.17, 173.96, 171.51, 162.78, 160.56, 143.81, 137.23, 136.67, 134.98, 133.27, 129.80, 128.52, 127.46, 127.32, 124.44, 122.75, 121.98, 120.19, 119.72, 119.11, 108.90, 108.43, 85.52, 79.69, 69.42, 51.83, 47.25, 40.61, 30.86, 29.68, 28.07, 26.59, 24.67. HRMS (ESI) m/z calcd for C37H29N3O5Na+ (M + Na)+ 618.2010, found 618.2005.
7′-cyclohexyl-1,5′-dimethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (3ak): A pink solid (35 mg, 57% yield); mp 292–294 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.52 (d, J = 7.8 Hz, 1H), 8.27 (d, J = 7.8 Hz, 1H), 7.99 (d, J = 7.8 Hz, 1H), 7.76 (t, J = 7.6 Hz, 1H), 7.64 (t, J = 7.5 Hz, 1H), 7.45 (t, J = 7.8 Hz, 1H), 7.10 (t, J = 7.7 Hz, 1H), 6.95 (t, J = 7.5 Hz, 1H), 6.76–6.65 (m, 3H), 6.54 (t, J = 7.7 Hz, 1H), 4.79 (d, J = 8.0 Hz, 1H), 4.56 (d, J = 8.0 Hz, 1H), 3.63 (dd, J = 16.3, 8.0 Hz, 1H), 3.33 (s, 3H), 3.00 (s, 3H), 1.88–1.65 (m, 4H), 1.50 (d, J = 12.5 Hz, 1H), 1.36 (d, J = 12.1 Hz, 2H), 1.16–0.98 (m, 3H). 13C NMR (101 MHz, CDCl3) δ 193.34, 178.23, 174.98, 173.92, 171.47, 162.77, 160.82, 143.82, 137.20, 136.66, 134.98, 133.24, 129.80, 128.52, 127.51, 127.30, 124.43, 122.74, 121.97, 120.25, 119.74, 119.12, 112.31, 108.87, 108.42, 86.00, 80.27, 69.43, 51.73, 47.22, 40.55, 30.86, 28.27, 28.19, 26.59, 25.69, 24.79. HRMS (ESI) m/z calcd for C38H31N3O5Na+ (M + Na)+ 632.2167, found 632.2161.
1,5′-dimethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (3al): A pink solid (33 mg, 63% yield); mp 271–273 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.58 (d, J = 7.7 Hz, 1H), 8.27 (d, J = 7.6 Hz, 1H), 7.98 (d, J = 7.4 Hz, 1H), 7.76 (t, J = 7.4 Hz, 1H), 7.63 (dd, J = 6.7, 8.0 Hz, 2H), 7.45 (t, J = 7.7 Hz, 1H), 7.11 (t, J = 7.7 Hz, 1H), 6.95 (t, J = 7.5 Hz, 1H), 6.76–6.65 (m, 3H), 6.56 (t, J = 7.6 Hz, 1H), 4.93 (d, J = 8.0 Hz, 1H), 4.69 (d, J = 8.1 Hz, 1H), 3.33 (s, 3H), 2.99 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 188.87, 178.25, 174.21, 173.12, 171.47, 162.41, 161.13, 137.16, 136.78, 135.06, 134.67, 133.35, 129.91, 128.90, 127.56, 127.35, 124.42, 122.88, 121.69, 120.23, 119.78, 118.87, 109.98, 108.89, 108.50, 85.40, 80.49, 68.87, 48.67, 42.40, 30.73, 26.61. HRMS (ESI) m/z calcd for C32H21N3O5Na+ (M + Na)+ 550.1384, found 550.1379.
7′-benzyl-1,5′-dimethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (3am): A pink solid (50 mg, 81% yield); mp 242–244 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.26–8.19 (m, 2H), 7.98 (d, J = 7.7 Hz, 1H), 7.76 (t, J = 7.4 Hz, 1H), 7.64 (t, J = 7.4 Hz, 1H), 7.41 (t, J = 7.6 Hz, 1H), 7.31–7.24 (m, 3H), 7.11–7.02 (m, 3H), 6.88 (t, J = 7.5 Hz, 1H), 6.74–6.51 (m, 4H), 4.89 (d, J = 8.1 Hz, 1H), 4.65 (d, J = 8.1 Hz, 1H), 4.38 (d, J = 14.1 Hz, 1H), 4.33 (d, J = 14.2 Hz, 1H), 3.32 (s, 3H), 2.99 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 193.27, 177.75, 174.46, 173.35, 171.41, 162.46, 160.75, 143.79, 137.38, 136.62, 135.02, 134.94, 134.79, 133.21, 132.72, 129.82, 128.98, 128.67, 128.47, 127.68, 127.42, 127.27, 124.42, 122.81, 121.90, 120.19, 119.47, 118.84, 112.41, 108.71, 108.45, 85.79, 80.92, 69.18, 47.54, 42.46, 41.08, 30.84, 26.59. HRMS (ESI) m/z calcd for C39H27N3O5Na+ (M + Na)+ 640.1848, found 640.1848.
7′-(2-chlorobenzyl)-1,5′-dimethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (3an): A pink solid (47 mg, 72% yield); mp 244–246 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.53 (d, J = 7.8 Hz, 1H), 8.23 (d, J = 7.8 Hz, 1H), 7.98 (d, J = 7.7 Hz, 1H), 7.74 (t, J = 7.5 Hz, 1H), 7.63 (t, J = 7.6 Hz, 1H), 7.42 (t, J = 7.8 Hz, 1H), 7.33 (t, J = 7.5 Hz, 1H), 7.30–7.16 (m, 2H), 7.12 (t, J = 7.7 Hz, 1H), 6.91 (t, J = 7.5 Hz, 2H), 6.75 (d, J = 7.8 Hz, 1H), 6.66 (t, J = 9.2 Hz, 2H), 6.56 (t, J = 7.7 Hz, 1H), 4.99 (d, J = 8.3 Hz, 1H), 4.74 (d, J = 8.3 Hz, 1H), 4.54 (s, 2H), 3.34 (s, 3H), 3.02 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 193.14, 178.40, 174.39, 172.99, 171.35, 162.68, 161.57, 143.50, 137.18, 136.87, 135.05, 134.72, 133.31, 132.57, 131.71, 129.91, 129.33, 128.78, 128.61, 128.03, 127.56, 127.37, 124.42, 122.88, 121.81, 120.53, 119.68, 118.91, 108.95, 108.51, 84.95, 80.88, 68.82, 47.62, 41.23, 40.38, 30.79, 26.63. HRMS (ESI) m/z calcd for C39H26N3O5NaCl+ (M + Na)+ 674.1453, found 674.1459.
7′-(3-chlorobenzyl)-1,5′-dimethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (3ao): A pink solid (48 mg, 73% yield); mp 349–351 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.22 (d, J = 7.7 Hz, 1H), 8.15 (d, J = 7.8 Hz, 1H), 7.97 (d, J = 7.6 Hz, 1H), 7.77 (dd, J = 10.7, 4.4 Hz, 1H), 7.65 (t, J = 6.9 Hz, 1H), 7.43 (t, J = 7.8 Hz, 1H), 7.33 (d, J = 8.0 Hz, 1H), 7.26–7.21 (m, 1H), 7.13–7.04 (m, 2H), 6.93–6.87 (m, 2H), 6.73 (d, J = 7.7 Hz, 1H), 6.65–6.51 (m, 3H), 4.89 (d, J = 8.1 Hz, 1H), 4.64 (d, J = 8.0 Hz, 1H), 4.32 (d, J = 13.8 Hz, 1H), 4.30 (d, J = 13.6 Hz, 1H), 3.33 (s, 3H), 2.99 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 193.32, 177.60, 174.32, 173.20, 171.42, 162.45, 160.69, 143.78, 137.34, 136.64, 135.06, 134.78, 134.33, 133.23, 130.10, 129.83, 129.03, 128.92, 128.16, 127.46, 127.24, 127.06, 124.41, 122.83, 121.81, 119.83, 119.64, 118.75, 108.69, 108.46, 85.80, 80.37, 69.35, 47.42, 41.83, 41.10, 30.84, 26.60. HRMS (ESI) m/z calcd for C39H26N3O5NaCl+ (M + Na)+ 674.1461, found 674.1459.
7′-(3-bromobenzyl)-1,5′-dimethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (3ap): A pink solid (52 mg, 75% yield); mp 234–236 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 7.8 Hz, 1H), 7.91 (d, J = 7.8 Hz, 1H), 7.74 (d, J = 7.7 Hz, 1H), 7.54 (t, J = 7.5 Hz, 1H), 7.42 (t, J = 7.5 Hz, 1H), 7.26–7.17 (m, 2H), 7.03–6.92 (m, 3H), 6.86 (t, J = 7.5 Hz, 1H), 6.74–6.65 (m, 2H), 6.49 (d, J = 7.8 Hz, 1H), 6.38 (dd, J = 7.3, 8.0 Hz, 2H), 6.28 (t, J = 7.6 Hz, 1H), 4.65 (d, J = 8.0 Hz, 1H), 4.40 (d, J = 8.0 Hz, 1H), 4.08 (d, J = 14.0 Hz, 1H), 4.03 (d, J = 14.1 Hz, 1H), 3.09 (s, 3H), 2.76 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 193.19, 177.58, 174.42, 173.23, 171.63, 162.26, 160.42, 143.91, 137.32, 136.96, 136.64, 135.06, 134.78, 133.24, 131.91, 131.09, 130.42, 129.83, 128.91, 127.56, 127.51, 127.24, 124.42, 122.82, 122.47, 121.81, 119.88, 119.69, 118.74, 108.69, 108.46, 85.76, 80.52, 69.29, 47.43, 41.76, 41.10, 30.85, 26.60. HRMS (ESI) m/z calcd for C39H26N3O5NaBr+ (M + Na)+ 718.0958, found 718.0954.
1,5′-dimethyl-7′-(4-methylbenzyl)-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (3aq): A pink solid (43 mg, 68% yield); mp 302–304 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.24 (dd, J = 7.1, 3.9 Hz, 2H), 7.98 (d, J = 7.7 Hz, 1H), 7.77 (t, J = 7.4 Hz, 1H), 7.64 (t, J = 7.2 Hz, 1H), 7.41 (t, J = 7.5 Hz, 1H), 7.08 (dd, J = 6.3, 7.4 Hz, 3H), 6.95–6.84 (m, 3H), 6.73 (d, J = 7.8 Hz, 1H), 6.65–6.58 (m, 2H), 6.52 (t, J = 7.6 Hz, 1H), 4.87 (d, J = 8.1 Hz, 1H), 4.62 (d, J = 8.1 Hz, 1H), 4.37–4.26 (m, 2H), 3.32 (s, 3H), 2.99 (s, 3H), 2.37 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 193.35, 177.98, 174.46, 173.35, 171.41, 162.45, 160.77, 143.79, 137.39, 137.33, 136.61, 135.01, 134.81, 133.21, 132.01, 129.80, 129.31, 128.94, 128.45, 127.42, 127.28, 124.42, 122.79, 121.92, 120.19, 119.36, 118.84, 108.70, 108.43, 85.79, 80.52, 69.17, 47.56, 42.19, 41.03, 30.83, 26.59, 21.18. HRMS (ESI) m/z calcd for C40H29N3O5Na+ (M + Na)+ 654.2008, found 654.2005.
7′-(4-methoxybenzyl)-1,5′-dimethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (3ar): A pink solid (40 mg, 62% yield); mp 344–346 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.24 (t, J = 7.2 Hz, 2H), 7.98 (d, J = 7.7 Hz, 1H), 7.77 (t, J = 7.5 Hz, 1H), 7.64 (d, J = 7.5 Hz, 1H), 7.41 (t, J = 7.8 Hz, 1H), 7.09 (t, J = 7.7 Hz, 1H), 6.98 (d, J = 8.4 Hz, 2H), 6.87 (d, J = 7.5 Hz, 1H), 6.75 (dd, J = 7.8, 8.1 Hz, 3H), 6.65–6.59 (m, 2H), 6.51 (t, J = 7.7 Hz, 1H), 4.86 (d, J = 8.1 Hz, 1H), 4.62 (d, J = 8.1 Hz, 1H), 4.34–4.23 (m, 2H), 3.86 (s, 3H), 3.32 (s, 3H), 2.99 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 193.32, 177.58, 174.28, 173.36, 171.28, 162.24, 160.53, 159.14, 143.79, 137.32, 136.60, 135.00, 134.73, 133.20, 129.98, 129.80, 128.95, 127.40, 127.36, 127.27, 124.42, 122.78, 121.78, 120.02, 119.36, 118.79, 114.07, 108.69, 108.43, 85.80, 80.63, 68.60, 55.36, 47.50, 41.88, 41.02, 30.82, 26.58. HRMS (ESI) m/z calcd for C40H29N3O6K+ (M + K)+ 686.1696, found 686.1693.
7′-(4-fluorobenzyl)-1,5′-dimethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (3as): A pink solid (36 mg, 57% yield); mp 335–337 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.20 (dd, J = 29.8, 7.7 Hz, 2H), 7.98 (d, J = 7.6 Hz, 1H), 7.78 (t, J = 7.4 Hz, 1H), 7.65 (t, J = 7.4 Hz, 1H), 7.41 (t, J = 7.6 Hz, 1H), 7.26 (d, J = 3.9 Hz, 2H), 7.09 (t, J = 7.6 Hz, 1H), 7.00–6.87 (m, 3H), 6.73 (d, J = 7.7 Hz, 1H), 6.66–6.50 (m, 3H), 4.89 (d, J = 8.0 Hz, 1H), 4.64 (d, J = 8.0 Hz, 1H), 4.31 (dd, J = 49.3, 14.1 Hz, 2H), 3.32 (s, 3H), 2.98 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 192.87, 177.51, 174.27, 173.26, 171.46, 162.29 (d, JF = 156 Hz), 160.73, 143.70, 137.33, 136.71, 135.08, 134.77, 133.68, 133.25, 130.04, 129.85, 128.90, 128.86, 127.42 (d, JF = 12 Hz), 127.30, 124.41, 122.83, 121.81, 120.03, 119.45, 118.62, 112.35, 108.70 (d, JF = 24 Hz), 108.46, 85.73, 80.47, 69.16, 47.51, 41.80, 41.02, 30.81, 26.60. 19F NMR (376 MHz, CDCl3) δ 85.04. HRMS (ESI) m/z calcd for C39H26N3O5NaF+ (M + Na)+ 658.1758.
7′-(4-chlorobenzyl)-1,5′-dimethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (3at): A pink solid (41 mg, 63% yield); mp 349–351 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.20 (t, J = 8.9 Hz, 2H), 7.98 (d, J = 7.7 Hz, 1H), 7.77 (t, J = 7.3 Hz, 1H), 7.65 (t, J = 7.3 Hz, 1H), 7.42 (t, J = 7.4 Hz, 1H), 7.13–6.87 (m, 6H), 6.73 (d, J = 7.7 Hz, 1H), 6.65–6.50 (m, 3H), 4.88 (d, J = 8.1 Hz, 1H), 4.36 (d, J = 14.1 Hz, 1H), 4.27 (d, J = 14.1 Hz, 1H), 3.32 (s, 3H), 2.99 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 193.05, 177.65, 174.34, 172.98, 171.34, 163.48, 162.41, 160.35, 143.76, 137.30, 136.68, 135.06, 134.74, 133.25, 130.72, 130.70, 130.49, 130.41, 129.84, 128.84, 127.39, 127.30, 124.41, 122.84, 121.74, 120.09, 119.43, 118.59, 115.64, 115.43, 108.72, 108.46, 85.61, 80.52, 69.00, 47.48, 41.72, 41.04, 30.82, 26.60. HRMS (ESI) m/z calcd for C39H26N3O5NaCl+ (M + Na)+ 674.1463, found 674.1459.
7′-(4-iodobenzyl)-1,5′-dimethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (3au): A pink solid (50 mg, 67% yield); mp 246–248 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.24 (d, J = 7.8 Hz, 1H), 8.13 (d, J = 7.7 Hz, 1H), 7.98 (d, J = 7.8 Hz, 1H), 7.78 (t, J = 7.5 Hz, 1H), 7.64 (dd, J = 6.8, 7.7 Hz, 3H), 7.41 (t, J = 7.7 Hz, 1H), 7.09 (t, J = 7.6 Hz, 1H), 6.93 (t, J = 7.5 Hz, 1H), 6.75 (dd, J = 6.9, 7.8 Hz, 3H), 6.56 (dt, J = 15.3, 8.3 Hz, 3H), 4.88 (d, J = 8.1 Hz, 1H), 4.63 (d, J = 8.1 Hz, 1H), 4.36 (d, J = 14.0 Hz, 1H), 4.20 (d, J = 14.1 Hz, 1H), 3.32 (s, 3H), 2.98 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 193.45, 177.52, 174.40, 173.23, 171.22, 162.36, 160.61, 143.75, 137.86, 137.28, 136.72, 135.09, 134.76, 134.41, 133.25, 130.63, 129.85, 128.91, 127.44, 127.31, 124.42, 122.83, 121.75, 120.06, 119.52, 118.63, 108.68, 108.47, 93.65, 85.81, 80.43, 68.99, 47.52, 41.98, 41.00, 30.82, 26.60. HRMS (ESI) m/z calcd for C39H26N3O5NaI+ (M + Na)+ 766.0822, found 766.0815.
1,5′-dimethyl-7′-phenethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (3av): A pink solid (51 mg, 80% yield); mp 171–173 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.52 (s, 1H), 8.29 (d, J = 7.7 Hz, 1H), 8.01 (d, J = 7.6 Hz, 1H), 7.78 (t, J = 7.5 Hz, 1H), 7.66 (t, J = 7.5 Hz, 1H), 7.47 (t, J = 7.8 Hz, 1H), 7.26–7.07 (m, 6H), 6.95 (t, J = 7.5 Hz, 1H), 6.72 (dd, J = 8.3, 7.9 Hz, 3H), 6.55 (t, J = 7.7 Hz, 1H), 4.88 (d, J = 8.0 Hz, 1H), 4.63 (d, J = 7.9 Hz, 1H), 3.46–3.39 (m, 2H), 3.35 (s, 3H), 3.03 (s, 3H), 2.52 (ddd, J = 31.9, 10.3, 6.0 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 193.22, 178.21, 174.58, 173.51, 171.47, 162.75, 160.76, 143.81, 137.73, 137.24, 136.80, 135.08, 134.89, 133.32, 129.88, 128.69, 128.56, 128.44, 127.55, 127.38, 126.53, 124.45, 122.82, 121.90, 120.24, 119.85, 119.00, 108.98, 108.49, 85.96, 80.49, 69.37, 47.52, 41.02, 39.87, 33.49, 30.88, 26.62. HRMS (ESI) m/z calcd for C40H29N3O5Na+ (M + Na)+ 654.2007, found 654.2005.
7′-(2-ethoxyethyl)-1,5′-dimethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (3aw): A pink solid (46 mg, 76% yield); mp 254–256 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.54 (d, J = 7.7 Hz, 1H), 8.26 (d, J = 7.8 Hz, 1H), 7.98 (d, J = 7.7 Hz, 1H), 7.76 (t, J = 7.5 Hz, 1H), 7.64 (t, J = 7.5 Hz, 1H), 7.45 (t, J = 7.7 Hz, 1H), 7.11 (t, J = 7.6 Hz, 1H), 6.94 (t, J = 7.5 Hz, 1H), 6.70 (dd, J = 7.2, 7.8 Hz, 3H), 6.54 (t, J = 7.7 Hz, 1H), 4.88 (d, J = 8.0 Hz, 1H), 4.64 (d, J = 8.0 Hz, 1H), 3.45–3.35 (m, 4H), 3.33 (s, 3H), 3.20 (dd, J = 15.5, 6.6 Hz, 2H), 3.01 (s, 3H), 1.08 (t, J = 7.0 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 193.07, 178.16, 174.58, 173.51, 171.43, 162.67, 160.82, 143.81, 137.24, 136.71, 135.01, 134.79, 133.28, 129.86, 128.60, 127.48, 127.37, 124.43, 122.81, 121.90, 120.12, 119.72, 118.99, 109.92, 108.94, 108.47, 85.78, 80.57, 69.26, 66.09, 66.02, 47.49, 41.06, 37.89, 30.84, 26.61, 14.92. HRMS (ESI) m/z calcd for C36H29N3O6Na+ (M + Na)+ 622.1962, found 622.1954.
1,5′-dimethyl-7′-(thiophen-2-ylmethyl)-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (3ax): A pink solid (48 mg, 77% yield); mp 277–279 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.23 (d, J = 7.7 Hz, 2H), 7.98 (d, J = 7.7 Hz, 1H), 7.78 (t, J = 7.3 Hz, 1H), 7.65 (t, J = 7.3 Hz, 1H), 7.44 (d, J = 7.5 Hz, 1H), 7.22 (d, J = 4.8 Hz, 1H), 7.09 (t, J = 7.6 Hz, 1H), 6.91 (dd, J = 9.3, 6.0 Hz, 2H), 6.75 (dd, J = 17.7, 5.1 Hz, 2H), 6.63 (dd, J = 15.8, 8.0 Hz, 2H), 6.53 (t, J = 7.6 Hz, 1H), 4.88 (d, J = 8.1 Hz, 1H), 4.63 (d, J = 8.1 Hz, 1H), 4.51 (s, 2H), 3.32 (s, 3H), 3.00 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 193.30, 177.74, 173.96, 172.91, 171.40, 162.48, 160.61, 143.78, 137.42, 136.62, 136.09, 135.04, 134.79, 133.20, 129.82, 129.06, 127.98, 127.44, 127.29, 126.84, 125.88, 124.43, 122.82, 121.87, 120.07, 119.43, 118.86, 108.71, 108.44, 85.80, 80.45, 69.20, 47.47, 41.05, 36.14, 30.84, 26.59. HRMS (ESI) m/z calcd for C37H25N3O5NaS+ (M + Na)+ 646.1420, found 646.1413.
1,5′-dimethyl-7′-(2-(thiophen-2-yl)ethyl)-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (3ay): A pink solid (49 mg, 79% yield); mp 235–237 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.52 (d, J = 7.8 Hz, 1H), 8.28 (d, J = 7.7 Hz, 1H), 8.00 (d, J = 7.7 Hz, 1H), 7.78 (t, J = 7.6 Hz, 1H), 7.66 (t, J = 7.5 Hz, 1H), 7.47 (t, J = 7.7 Hz, 1H), 7.11 (dd, J = 6.6, 5.9 Hz, 2H), 6.95 (t, J = 7.5 Hz, 1H), 6.86 (d, J = 4.9 Hz, 1H), 6.72 (dd, J = 6.5, 8.8 Hz, 4H), 6.55 (t, J = 7.7 Hz, 1H), 4.88 (d, J = 8.0 Hz, 1H), 4.63 (d, J = 8.0 Hz, 1H), 3.45 (d, J = 6.8 Hz, 2H), 3.34 (s, 3H), 3.02 (s, 3H), 2.84–2.66 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 192.97, 178.23, 174.51, 173.43, 171.44, 162.73, 160.58, 143.71, 139.64, 137.25, 136.84, 135.08, 134.86, 133.33, 129.89, 128.53, 127.58, 127.38, 126.85, 125.51, 124.44, 123.94, 122.83, 121.78, 120.16, 119.89, 118.83, 108.97, 108.49, 85.90, 80.17, 69.14, 47.51, 41.02, 39.89, 30.86, 27.43, 26.61. HRMS (ESI) m/z calcd for C38H27N3O5NaS+ (M + Na)+ 660.1570, found 660.1569.
7′-(1H-indol-5-yl)-1,5′-dimethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (3az): A pink solid (34 mg, 53% yield); mp 272–274 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, DMSO-d6) δ 11.24 (s, 1H), 8.49 (d, J = 7.7 Hz, 1H), 8.18 (d, J = 7.7 Hz, 1H), 7.89 (dd, J = 6.9, 7.6 Hz, 2H), 7.77 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.6 Hz, 1H), 7.38–7.32 (m, 2H), 7.16 (d, J = 7.7 Hz, 1H), 7.02–6.90 (m, 4H), 6.57 (dt, J = 7.1, 8.0 Hz, 3H), 6.40 (s, 1H), 4.92 (d, J = 8.1 Hz, 1H), 4.65 (d, J = 8.0 Hz, 1H), 3.28 (s, 3H), 2.96 (s, 3H). 13C NMR (101 MHz, DMSO-d6) δ 193.59, 177.52, 175.54, 174.13, 170.43, 163.35, 161.37, 144.47, 137.44, 137.03, 136.96, 136.16, 135.62, 134.63, 134.44, 130.51, 127.88, 127.76, 127.67, 127.45, 127.24, 123.62, 123.56, 122.74, 122.03, 120.52, 120.02, 119.09, 119.00, 111.75, 110.03, 109.98, 109.83, 101.86, 85.22, 80.94, 68.56, 48.48, 41.47, 28.76, 26.93. HRMS (ESI) m/z calcd for C40H26N4O5Na+ (M + Na)+ 665.1804, found 665.1801.
1,5′-diethyl-7′-methyl-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (4a): A pink solid (44 mg, 78% yield); mp 326–328 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.54 (d, J = 7.8 Hz, 1H), 8.26 (d, J = 7.8 Hz, 1H), 8.00 (d, J = 7.8 Hz, 1H), 7.76 (t, J = 7.5 Hz, 1H), 7.64 (t, J = 7.4 Hz, 1H), 7.43 (t, J = 7.7 Hz, 1H), 7.09 (t, J = 7.7 Hz, 1H), 6.91 (t, J = 7.5 Hz, 1H), 6.75 (d, J = 7.8 Hz, 1H), 6.64 (t, J = 6.8 Hz, 2H), 6.52 (t, J = 7.7 Hz, 1H), 4.80 (d, J = 7.9 Hz, 1H), 4.65 (d, J = 7.9 Hz, 1H), 3.89 (q, J = 7.5 Hz, 2H), 3.54–3.34 (m, 2H), 2.71 (s, 3H), 1.37 (t, J = 7.1 Hz, 3H), 0.96 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 193.27, 178.25, 174.80, 171.07, 161.33, 161.22, 142.69, 137.22, 136.78, 134.95, 134.81, 133.23, 129.80, 128.85, 127.46, 127.37, 124.66, 122.66, 122.14, 119.73, 119.17, 118.58, 108.43, 108.30, 85.46, 80.93, 69.21, 47.28, 41.53, 38.41, 34.93, 24.60, 13.82, 12.18. HRMS (ESI) m/z calcd for C35H27N3O5Na+ (M + Na)+ 592.1854, found 592.1848.
1,2′,5,5′,7′-pentamethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (4b): A pink solid (34 mg, 59% yield); mp 331–333 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.32–8.25 (m, 2H), 8.00 (d, J = 7.5 Hz, 1H), 7.79 (d, J = 7.9 Hz, 1H), 7.66 (d, J = 7.6 Hz, 1H), 7.28 (d, J = 8.0 Hz, 1H), 6.91 (d, J = 7.9 Hz, 1H), 6.65–6.59 (m, 2H), 6.45 (s, 1H), 4.86 (d, J = 8.0 Hz, 1H), 4.63 (d, J = 8.0 Hz, 1H), 3.31 (s, 3H), 2.99 (s, 3H), 2.70 (s, 3H), 2.38 (s, 3H), 1.88 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 193.51, 178.15, 174.63, 173.93, 171.33, 161.21, 141.34, 138.35, 137.33, 134.98, 134.93, 133.20, 132.08, 130.21, 129.26, 128.20, 127.42, 127.36, 125.24, 121.90, 119.38, 118.97, 108.78, 108.13, 85.90, 80.28, 68.99, 47.73, 41.19, 31.03, 26.60, 24.61, 21.22, 20.79. HRMS (ESI) m/z calcd for C35H27N3O5Na+ (M + Na)+ 592.1851, found 592.1848.
2′,5-difluoro-1,5′,7′-trimethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (4c): A pink solid (32 mg, 55% yield); mp 232–234 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.25 (dd, J = 6.0, 6.7 Hz, 2H), 8.01 (d, J = 7.7 Hz, 1H), 7.81 (t, J = 7.2 Hz, 1H), 7.69 (t, J = 7.1 Hz, 1H), 7.24–7.16 (m, 1H), 6.84 (dd, J = 8.6, 6.6 Hz, 1H), 6.66 (ddd, J = 6.9, 8.7, 3.8 Hz, 2H), 6.39 (d, J = 6.7 Hz, 1H), 4.87 (d, J = 8.0 Hz, 1H), 4.64 (d, J = 7.9 Hz, 1H), 3.32 (s, 3H), 3.00 (s, 3H), 2.72 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 193.51, 178.15, 174.63 (d, JF = 70 Hz), 173.93, 171.33, 161.32 (d, JF = 4 Hz), 161.28, 141.34, 138.35, 137.33, 134.98 (d, JF = 5 Hz), 134.93, 133.20 (d, JF = 112 Hz), 132.08, 130.21, 129.26, 128.20, 127.42 (d, JF = 6 Hz), 127.36, 125.24, 121.90, 119.38, 118.97, 108.78 (d, JF = 65 Hz), 108.13, 85.90, 80.28, 68.99, 47.73, 41.19, 31.03, 26.60, 24.61, 21.22, 20.79. 1HRMS (ESI) m/z calcd for C33H21N3O5NaF2+ (M + Na)+ 600.1353, found 600.1347.
2′,5-dichloro-1,5′,7′-trimethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (4d): A pink solid (32 mg, 52% yield); mp 240–242 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.55 (s, 1H), 8.32 (d, J = 7.6 Hz, 1H), 8.06 (d, J = 7.6 Hz, 1H), 7.87 (t, J = 7.5 Hz, 1H), 7.75 (t, J = 7.1 Hz, 1H), 7.46 (d, J = 8.2 Hz, 1H), 7.17 (d, J = 8.0 Hz, 1H), 6.76–6.63 (m, 3H), 4.89 (d, J = 7.8 Hz, 1H), 4.67 (d, J = 7.9 Hz, 1H), 3.37 (s, 3H), 3.04 (s, 3H), 2.77 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 192.78, 178.13, 174.40, 173.45, 170.86, 160.88, 158.79, 142.40, 136.91, 136.73, 135.38, 134.79, 133.72, 130.17, 128.12, 127.73, 127.62, 127.51, 125.13, 124.64, 123.35, 120.89, 119.51, 110.07, 109.52, 85.92, 80.33, 69.41, 47.24, 41.11, 31.05, 26.78, 24.76. HRMS (ESI) m/z calcd for C33H21N3O5NaCl2+ (M + Na)+ 632.0759, found 632.0756.
3′,6-dimethoxy-1,5′,7′-trimethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (4e): An orange solid (44 mg, 73% yield); mp 211–213 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.55 (t, J = 9.3 Hz, 1H), 8.33 (d, J = 7.6 Hz, 1H), 8.07 (d, J = 7.5 Hz, 1H), 7.85 (t, J = 7.0 Hz, 1H), 7.75–7.69 (m, 1H), 6.69–6.59 (m, 2H), 6.39 (s, 1H), 6.23–6.08 (m, 2H), 4.90 (d, J = 8.0 Hz, 1H), 4.67 (d, J = 8.0 Hz, 1H), 3.94 (s, 3H), 3.71 (s, 3H), 3.40 (s, 3H), 3.09 (s, 3H), 2.81 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 193.62, 177.75, 175.03, 173.96, 171.97, 167.71, 165.12, 161.02, 160.26, 137.40, 134.93, 132.68, 129.93, 127.25, 125.35, 116.36, 113.78, 113.15, 112.40, 109.06, 106.31, 96.42, 92.62, 86.21, 69.00, 55.63, 55.24, 47.93, 41.37, 30.64, 29.68, 26.59, 24.59. HRMS (ESI) m/z calcd for C35H27N3O7Na+ (M + Na)+ 624.1752, found 624.1747.
3′,6-dichloro-1,5′,7′-trimethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (4f): An orange solid (40 mg, 66% yield); mp 327–329 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.43 (d, J = 8.3 Hz, 1H), 8.24 (d, J = 7.8 Hz, 1H), 8.00 (d, J = 7.8 Hz, 1H), 7.80 (d, J = 7.3 Hz, 1H), 7.69 (d, J = 7.5 Hz, 1H), 6.91 (d, J = 8.3 Hz, 1H), 6.75 (s, 1H), 6.67 (s, 1H), 6.54 (s, 2H), 4.83 (d, J = 8.0 Hz, 1H), 4.61 (d, J = 8.0 Hz, 1H), 3.32 (s, 3H), 2.98 (s, 3H), 2.72 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 192.96, 178.33, 174.48, 173.42, 170.93, 162.47, 159.03, 144.82, 143.46, 136.86, 136.01, 135.25, 134.68, 133.63, 129.28, 127.58, 127.53, 125.18, 122.78, 120.66, 120.38, 119.89, 117.22, 109.39, 109.26, 85.83, 80.28, 69.21, 47.32, 41.19, 30.74, 26.75, 24.70. HRMS (ESI) m/z calcd for C33H21N3O5NaCl2+ (M + Na)+ 632.0748, found 632.0756.
3′,6-dibromo-1,5′,7′-trimethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indolne-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (4g): An orange solid (42 mg, 60% yield); mp 351–353 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.35 (d, J = 8.3 Hz, 1H), 8.24 (d, J = 7.8 Hz, 1H), 8.01 (d, J = 7.6 Hz, 1H), 7.79 (t, J = 7.6 Hz, 1H), 7.69 (t, J = 7.4 Hz, 1H), 7.07 (d, J = 8.3 Hz, 1H), 6.87 (d, J = 7.1 Hz, 2H), 6.70 (d, J = 8.3 Hz, 1H), 6.47 (d, J = 8.2 Hz, 1H), 4.83 (d, J = 8.0 Hz, 1H), 4.60 (d, J = 8.0 Hz, 1H), 3.31 (s, 3H), 2.98 (s, 3H), 2.72 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 192.77, 178.28, 178.24, 174.50, 173.54, 173.45, 171.03, 162.54, 159.29, 144.86, 136.93, 135.26, 134.74, 133.65, 132.32, 129.29, 127.60, 127.54, 125.75, 125.45, 124.01, 123.45, 120.68, 120.47, 119.51, 117.59, 112.32, 112.18, 85.62, 80.53, 69.13, 47.26, 41.19, 30.73, 26.75, 24.70. HRMS (ESI) m/z calcd for C33H21N3O5NaBr2+ (M + Na)+ 719.9745, found 719.9746.
1,4′,5′,7,7′-pentamethyl-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (4h): A pink solid (37 mg, 65% yield); mp 286–288 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.48 (d, J = 8.0 Hz, 1H), 8.25 (d, J = 7.7 Hz, 1H), 7.99 (d, J = 7.6 Hz, 1H), 7.76 (t, J = 7.5 Hz, 1H), 7.64 (t, J = 7.6 Hz, 1H), 7.18 (d, J = 7.4 Hz, 1H), 6.89–6.81 (m, 2H), 6.50 (d, J = 7.9 Hz, 1H), 6.40 (t, J = 7.7 Hz, 1H), 4.92 (d, J = 7.9 Hz, 1H), 4.62 (d, J = 7.9 Hz, 1H), 3.63 (s, 3H), 3.28 (s, 3H), 2.71 (s, 3H), 2.51 (s, 3H), 2.42 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 193.19, 178.31, 174.86, 173.70, 172.51, 161.32, 141.59, 139.97, 137.24, 136.98, 134.97, 134.70, 133.73, 133.14, 127.52, 127.29, 126.77, 122.55, 122.46, 122.29, 120.71, 120.32, 120.18, 119.84, 119.30, 86.46, 79.94, 69.28, 47.93, 41.50, 34.38, 30.18, 24.58, 19.77, 19.52. HRMS (ESI) m/z calcd for C35H27N3O5Na+ (M + Na)+ 592.1846, found 592.1848.
7′-phenyl-1,5′-dipropyl-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (4j): A pink solid (38 mg, 58% yield); mp 341–343 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, DMSO-d6) δ 8.48 (d, J = 7.6 Hz, 1H), 8.19–8.15 (m, 1H), 7.87 (dd, J = 22.9, 7.3 Hz, 2H), 7.73 (d, J = 7.3 Hz, 1H), 7.44 (t, J = 7.4 Hz, 1H), 7.33 (dd, J = 15.1, 7.4 Hz, 3H), 7.14–7.08 (m, 1H), 6.89 (ddd, J = 7.6, 8.1, 6.2 Hz, 5H), 6.54 (t, J = 6.1 Hz, 2H), 4.90 (d, J = 8.0 Hz, 1H), 4.64 (d, J = 7.9 Hz, 1H), 3.84–3.60 (m, 3H), 3.45–3.38 (m, 1H), 1.71 (dd, J = 14.5, 7.4 Hz, 2H), 1.28–1.23 (m, 2H), 1.04 (t, J = 7.4 Hz, 3H), 0.54 (t, J = 7.3 Hz, 3H). 13C NMR (101 MHz, DMSO-d6) δ 193.10, 177.80, 174.48, 172.90, 170.84, 162.47, 161.41, 143.66, 137.28, 136.98, 135.80, 134.66, 134.09, 132.09, 130.49, 129.33, 128.99, 127.97, 127.58, 127.33, 127.18, 123.90, 122.53, 121.90, 119.45, 118.46, 112.53, 109.55, 85.92, 81.08, 69.30, 48.03, 45.85, 41.81, 22.22, 20.67, 11.77, 10.88. HRMS (ESI) m/z calcd for C42H33N3O5Na+ (M + Na)+ 682.2325, found 682.2318.
1,3′,5′,6-tetramethyl-7′-phenyl-5b′,8a′-dihydro-5′H,6′H-spiro[indolne-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (4k): An orange solid (41 mg, 65% yield); mp 243–245 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.49 (d, J = 8.0 Hz, 1H), 8.24 (d, J = 7.8 Hz, 1H), 7.98 (d, J = 7.7 Hz, 1H), 7.72 (t, J = 7.6 Hz, 1H), 7.60 (t, J = 7.5 Hz, 1H), 7.38–7.21 (m, 3H), 6.93 (d, J = 7.5 Hz, 2H), 6.78 (d, J = 8.1 Hz, 1H), 6.63–6.55 (m, 2H), 6.47 (s, 1H), 6.37 (d, J = 7.9 Hz, 1H), 5.01 (d, J = 8.1 Hz, 1H), 4.77 (d, J = 8.1 Hz, 1H), 3.34 (s, 3H), 3.02 (s, 3H), 2.35 (s, 3H), 2.17 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 193.47, 178.22, 174.12, 173.03, 171.84, 163.29, 160.81, 148.90, 143.88, 140.25, 137.32, 134.94, 133.06, 131.30, 129.21, 128.73, 128.16, 127.54, 127.31, 126.63, 124.24, 123.43, 121.77, 118.90, 118.76, 116.90, 109.43, 86.51, 79.75, 69.51, 47.86, 41.30, 30.79, 26.59, 22.96, 21.60. HRMS (ESI) m/z calcd for C40H29N3O5Na+ (M + Na)+ 654.2012, found 654.2005.
3′,6-dimethoxy-1,5′-dimethyl-7′-phenyl-5b′,8a′-dihydro-5′H,6′H-spiro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (4l): An orange solid (48 mg, 73% yield); mp 232–234 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.54 (d, J = 8.7 Hz, 1H), 8.23 (d, J = 7.6 Hz, 1H), 7.98 (d, J = 7.7 Hz, 1H), 7.72 (t, J = 7.4 Hz, 1H), 7.59 (t, J = 7.4 Hz, 1H), 7.39–7.20 (m, 3H), 6.94 (d, J = 7.4 Hz, 2H), 6.64 (d, J = 8.5 Hz, 1H), 6.52 (d, J = 8.7 Hz, 1H), 6.32 (s, 1H), 6.07 (d, J = 8.8 Hz, 2H), 4.97 (d, J = 8.1 Hz, 1H), 4.74 (d, J = 8.1 Hz, 1H), 3.83 (s, 3H), 3.64 (s, 3H), 3.33 (s, 3H), 3.02 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 193.77, 173.99, 173.31, 172.13, 167.80, 161.22, 160.24, 145.20, 137.44, 134.90, 134.80, 132.92, 132.45, 130.07, 129.22, 128.61, 127.40, 127.24, 126.63, 125.55, 116.43, 113.66, 112.98, 110.02, 109.14, 106.50, 96.66, 92.78, 86.84, 55.57, 55.26, 48.03, 41.27, 30.65, 26.56. HRMS (ESI) m/z calcd for C40H29N3O7Na+ (M + Na)+ 686.1898, found 686.1903.
3′,6-difluoro-1,5′-dimethyl-7′-phenyl-5b′,8a′-dihydro-5′H,6′H-spro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (4m): An orange solid (35 mg, 54% yield); mp 165–167 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.61 (dd, J = 8.6, 5.9 Hz, 1H), 8.24 (d, J = 7.7 Hz, 1H), 8.00 (d, J = 7.6 Hz, 1H), 7.70 (dt, J = 43.3, 7.5 Hz, 3H), 7.32 (dt, J = 21.8, 7.2 Hz, 2H), 6.92 (d, J = 7.3 Hz, 2H), 6.67 (dd, J = 8.0, 6.0 Hz, 2H), 6.51 (dd, J = 8.5, 2.1 Hz, 1H), 6.37–6.26 (m, 2H), 4.99 (d, J = 8.1 Hz, 1H), 4.76 (d, J = 8.1 Hz, 1H), 3.34 (s, 3H), 3.02 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 192.84, 178.38, 173.88, 172.65 (d, JF = 119 Hz), 171.46, 170.58, 167.85 (d, JF = 279 Hz), 165.06, 164.47, 164.25, 159.35, 145.53, 136.99, 135.19, 134.86, 133.49, 131.17(d, JF = 59 Hz), 130.58, 130.46, 129.29, 128.89, 127.65 (d, JF = 20 Hz), 127.45, 126.50, 125.76 (d, JF = 9 Hz), 125.67 (d, J = 19.8 Hz), 109.18, 108.96 (d, JF = 22 Hz), 108.67, 108.40, 97.67, 97.39, 96.68, 96.39, 86.81, 69.60, 47.54, 41.23, 30.85, 29.68, 26.81. 19F NMR (376 MHz, CDCl3) δ −96.76, −108.84. HRMS (ESI) m/z calcd for C38H23N3O5NaF2+ (M + Na)+ 662.1500, found 662.1503.
3′,6-dichloro-1,5′-dimethyl-7′-phenyl-5b′,8a′-dihydro-5′H,6′H-spro[indoline-3,15′-[5a,8b]methanonaphtho[2,3-c]pyrrolo[3,4-a]carbazole]-2,6′,8′,9′,14′(7′H)-pentaone (4n): An orange solid (46 mg, 68% yield); mp 347–349 °C; purified over a column of silica gel (petroleum ether/EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 8.52 (d, J = 8.1 Hz, 1H), 8.24 (d, J = 7.2 Hz, 1H), 8.00 (d, J = 7.3 Hz, 1H), 7.70 (dd, J = 34.4, 7.1 Hz, 2H), 7.32 (dd, J = 14.1, 6.7 Hz, 3H), 6.91 (s, 3H), 6.77 (s, 1H), 6.62 (dd, J = 22.1, 14.2 Hz, 3H), 4.99 (d, J = 7.8 Hz, 1H), 4.77 (d, J = 7.7 Hz, 1H), 3.34 (s, 3H), 3.01 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 192.84, 178.33, 173.83, 172.60, 171.11, 162.68, 159.21, 144.95, 143.63, 136.91, 136.08, 135.25, 134.86, 133.63, 131.09, 129.31, 129.09, 128.93, 127.71, 127.52, 126.47, 125.22, 122.80, 120.88, 120.56, 119.87, 117.35, 109.45, 109.40, 86.24, 79.50, 69.53, 47.41, 41.23, 30.83, 26.79. HRMS (ESI) m/z calcd for C38H23N3O5NaCl+ (M + Na)+ 694.0917, found 694.0912.

4. Conclusions

In summary, a strategy for the direct synthesis of novel polycyclic N-heterocycle-fused naphthoquinones by merging intramolecular oxidative coupling and cascade [4 + 2] cycloaddition is presented. In the protocol, mechanistic investigations suggest that the cascade reaction involves the intermediate spiro polycyclic N-heterocycles and [4 + 2] cycloaddition processes. The notable features of this method include easily obtainable substrates and compatibility of good functional groups in the formation of the products. Further application of the method for the preparation of new luminescent material molecules is ongoing in our group. The synthetic compounds exhibit interesting fluorescence properties, and the selective sensing of TFA experiments was conducted to show the application in fluorescent probes.

Supplementary Materials

The following supporting information can be downloaded at https://www.mdpi.com/article/10.3390/molecules29235639/s1: Figure S1: DFT calculation; Figures S2–S8: Experimental Section for Photo-Physical Studies; Figures S9–S10: Crystal data and structure refinement of product 5ae and 6i; Figures S11–S92: Copies of 1H, 13C, and 19F NMR spectra for all compounds. Tables S1–S6: Optimization of reaction conditions; Table S7: Photophysical characterization data of all compounds; Tables S8–S22: Crystal data and structure refinement of product 5ae and 6i (see [36,37,38]).

Author Contributions

Conceptualization, Y.D.; methodology, L.C. and H.-Q.W.; investigation, L.X. and J.-H.Y.; resources, F.Y. and Y.-T.W.; data curation Z.-F.W.; visualization, Y.-R.L.; funding acquisition, G.-W.D. All authors have read and agreed to the published version of the manuscript.

Funding

We are grateful for the support from the Opening Project of Structural Optimization and Application of Functional Molecules Key Laboratory of Sichuan Province (2023GNFZ-06) and Project supported by Natrual Science Foundation of Sichuan Province (25QNJJ1390), the financial support from the project supported by the National undergraduate training program for innovation and entrepreneurship (Grant No. 202414389032 and S202414389150), the financial support from the Foundation of Applied Basic Research Project of Sichuan Provincial Science and Technology Department (2023YFG0237), and the Foundation of Chengdu Normal University Talent Introduction Research Funding (CS23XMPY0103).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The original contributions presented in the study are included in the article/Supplementary Materials, further inquiries can be directed to the corresponding author/s.

Acknowledgments

We are grateful to HZWTECH for providing the computation facilities.

Conflicts of Interest

The authors declare no conflicts of interest.

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Molecules 29 05639 g001
Figure 1. The representative examples of polycyclic N-heterocycles.
Figure 1. The representative examples of polycyclic N-heterocycles.
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Molecules 29 05639 sch001
Scheme 1. The synthesis of novel polycyclic N-heterocycle-fused naphthoquinones. (a) Our previous work [31]. (b) This work.
Scheme 1. The synthesis of novel polycyclic N-heterocycle-fused naphthoquinones. (a) Our previous work [31]. (b) This work.
Molecules 29 05639 sch001
Molecules 29 05639 sch002
Scheme 2. Control experiments for obtaining polycyclic N-heterocycles.
Scheme 2. Control experiments for obtaining polycyclic N-heterocycles.
Molecules 29 05639 sch002
Molecules 29 05639 sch003
Scheme 3. Plausible reaction mechanism.
Scheme 3. Plausible reaction mechanism.
Molecules 29 05639 sch003
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Figure 2. Some compounds (3ac, 3ai, 3an, 3as, 3ay, 4k, 4m) under 365 nm UV.
Figure 2. Some compounds (3ac, 3ai, 3an, 3as, 3ay, 4k, 4m) under 365 nm UV.
Molecules 29 05639 g002
Molecules 29 05639 g003
Figure 3. Colorimetric responses of 3aa (5 × 10−5 M) in DCM after the addition of 1000 equiv of different acids (H3PO4, H2SO4, HCl, HNO3, TFA = trifluoroacetic acid, BZA = benzoic acid, OA = oxalic acid, HOAc, PBA = phenylboronic acid, BSA = benzenesulfonic acid).
Figure 3. Colorimetric responses of 3aa (5 × 10−5 M) in DCM after the addition of 1000 equiv of different acids (H3PO4, H2SO4, HCl, HNO3, TFA = trifluoroacetic acid, BZA = benzoic acid, OA = oxalic acid, HOAc, PBA = phenylboronic acid, BSA = benzenesulfonic acid).
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Molecules 29 05639 g004
Figure 4. Changes in the fluorescence spectra of 3aa (5 × 10−5 M) with acid.
Figure 4. Changes in the fluorescence spectra of 3aa (5 × 10−5 M) with acid.
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Table 1. Optimization of the reaction conditions a.
Table 1. Optimization of the reaction conditions a.
Molecules 29 05639 i001
EntryVariation from the Standard ConditionsYield (%)b 3aa
1Standard conditions82
2Other palladium catalyst instead of Pd(OTf)2<50
3Other catalyst instead of AgOAc<40
4Other oxidants instead of K2S2O8<60
51 equiv instead of 3 equiv of HOAc76
680 °C instead of 100 °C61
7DMSO instead of CH3CN<10
a Standard conditions: 1a (0.1 mmol), 2a (0.3 mmol) Pd(OTf)2 (30 mol%), K2S2O8 (2 equiv), AgOAc (30 mol%), HOAc (3 equiv), CH3CN (2 mL), 100 °C, sealed tube for 1 h. b Isolated yields.
Table 2. Scope of maleimides a.
Table 2. Scope of maleimides a.
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Molecules 29 05639 i003
a Reaction conditions: 1a (0.1 mmol), 2 (0.3 mmol) Pd(OTf)2 (30 mol%), K2S2O8 (2 equiv), AgOAc (30 mol%), HOAc (3 equiv), CH3CN (2 mL), 100 °C, sealed tube for 1 h. Isolated yields are indicated.
Table 3. Scope for bi-indolylnaphthoquinones a.
Table 3. Scope for bi-indolylnaphthoquinones a.
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Molecules 29 05639 i005
a Reaction conditions: 1 (0.1 mmol), 2 (0.3 mmol) Pd(OTf)2 (30 mol%), K2S2O8 (2 equiv), AgOAc (30 mol%), HOAc (3 equiv), CH3CN (2 mL), 100 °C, sealed tube for 1 h. Isolated yields are indicated.
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Dong, Y.; Chen, L.; Wu, H.-Q.; Xie, L.; Yu, J.-H.; Yang, F.; Wang, Y.-T.; Liu, Y.-R.; Deng, G.-W.; Wang, Z.-F. Pd/Ag-Cocatalyzed Merging Intramolecular Oxidative Coupling and Cascade [4 + 2] Cycloaddition: Synthesis and Photophysical Properties of Novel Polycyclic N-Heterocycles Fused Naphthoquinones. Molecules 2024, 29, 5639. https://doi.org/10.3390/molecules29235639

AMA Style

Dong Y, Chen L, Wu H-Q, Xie L, Yu J-H, Yang F, Wang Y-T, Liu Y-R, Deng G-W, Wang Z-F. Pd/Ag-Cocatalyzed Merging Intramolecular Oxidative Coupling and Cascade [4 + 2] Cycloaddition: Synthesis and Photophysical Properties of Novel Polycyclic N-Heterocycles Fused Naphthoquinones. Molecules. 2024; 29(23):5639. https://doi.org/10.3390/molecules29235639

Chicago/Turabian Style

Dong, Yu, Lin Chen, Han-Qing Wu, Li Xie, Jing-Hao Yu, Fan Yang, Yu-Ting Wang, Yu-Rong Liu, Guo-Wei Deng, and Zhi-Fan Wang. 2024. "Pd/Ag-Cocatalyzed Merging Intramolecular Oxidative Coupling and Cascade [4 + 2] Cycloaddition: Synthesis and Photophysical Properties of Novel Polycyclic N-Heterocycles Fused Naphthoquinones" Molecules 29, no. 23: 5639. https://doi.org/10.3390/molecules29235639

APA Style

Dong, Y., Chen, L., Wu, H. -Q., Xie, L., Yu, J. -H., Yang, F., Wang, Y. -T., Liu, Y. -R., Deng, G. -W., & Wang, Z. -F. (2024). Pd/Ag-Cocatalyzed Merging Intramolecular Oxidative Coupling and Cascade [4 + 2] Cycloaddition: Synthesis and Photophysical Properties of Novel Polycyclic N-Heterocycles Fused Naphthoquinones. Molecules, 29(23), 5639. https://doi.org/10.3390/molecules29235639

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