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Article

Oxidative Dearomative Cross-Dehydrogenative Coupling of Indoles with Diverse C-H Nucleophiles: Efficient Approach to 2,2-Disubstituted Indolin-3-ones

by
Xue Yan
1,2,
Ying-De Tang
1,2,
Cheng-Shi Jiang
2,
Xigong Liu
2,3,* and
Hua Zhang
2,*
1
School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, China
2
School of Biological Science and Technology, University of Jinan, Jinan 250022, China
3
School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China
*
Authors to whom correspondence should be addressed.
Molecules 2020, 25(2), 419; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25020419
Submission received: 23 December 2019 / Revised: 12 January 2020 / Accepted: 15 January 2020 / Published: 20 January 2020
(This article belongs to the Special Issue Advances in Cross-Coupling Reactions)
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Abstract

:
The oxidative, dearomative cross-dehydrogenative coupling of indoles with various C-H nucleophiles is developed. This process features a broad substrate scope with respect to both indoles and nucleophiles, affording structurally diverse 2,2-disubstituted indolin-3-ones in high yields (up to 99%). The oxidative dimerization and trimerization of indoles has also been demonstrated under the same conditions.

Graphical Abstract

1. Introduction

Direct C-H functionalization has emerged as an elegant approach to the construction of C-C bonds [1,2,3,4,5,6,7]. Particularly, oxidative cross-dehydrogenative coupling (CDC) from two readily available C-H bonds features the advantage of high step- and atom-economy, as it does not require pre-functionalized substrates [8,9,10,11,12]. Over the past decades, oxidative CDC reactions have gained tremendous attention since the pioneering work of Li, and numerous oxidative systems have been successfully developed [13,14,15,16,17,18]. Under the developed oxidative conditions, indoles have been widely used as nucleophiles in a number of CDC reactions owing to the strong nucleophilicity of indole rings [19,20,21,22,23,24,25,26,27,28,29]. In contrast, reactions of indoles with other nucleophiles have not been well investigated [30,31,32,33,34,35]. Therefore, the development of CDC reactions from indoles with various C-H nucleophiles will provide straightforward access to structurally diverse indole derivatives and is thus highly desired.
As illustrated in Figure 1, 2,2-disubstituted indolin-3-ones are core scaffolds of a wide range of bioactive molecules [36,37,38,39,40,41,42], and have also been widely used as key intermediates in the total synthesis of a variety of natural products [43,44,45,46,47,48]. Therefore, great efforts have been devoted to the construction of these structures. Current syntheses are mainly based on four strategies, i.e., the oxidative rearrangement of 2,3-disubstituted indoles [49,50,51,52,53], cyclization reactions from acyclic starting materials [54,55,56,57,58,59,60,61,62], direct transformation from corresponding 3H-indol-3-ones or indolin-3-ones [63,64,65,66,67,68,69,70,71], and oxidative dearomatization of indoles [72,73,74,75,76]. Direct C-H functionalization of indoles with different C-H nucleophiles presents an atom-economic protocol without prior installation of activating groups and is thus very attractive. However, most of these reactions focus on the construction of di- or trimerization of indoles [50,77,78,79,80], and the reactions of indoles with dissimilar C-H nucleophiles are considerably rare [81,82,83]. Recently, we reported an efficient oxidative dearomatization reaction of indoles [84,85]. Encouraged by these results, we envisioned that oxidative dearomatization of indoles with C-H nucleophiles could be achieved under suitable conditions. Herein, we present an effective oxidative, dearomative cross-dehydrogenative coupling of indoles with a variety of C-H nucleophiles (Figure 2), affording structurally diverse 2,2-disubstituted indolin-3-ones in high yields.

2. Results and Discussion

The reaction of 2-phenyl-indole 1a with diethyl malonate 2a was initially selected to start our investigation in the presence of TEMPO+ClO4− (TEMPO oxoammonium perchlorate) (Table 1). No expected product was observed when the reaction was conducted without any additive, while the dimerization product (6a) of 1a was obtained in 96% yield (Table 1, entry 1). To improve the nucleophilicity of 2a, various metal additives were applied to activate the 1,3-dicarbonyls. To our delight, the desired product 3a was obtained in 79% yield using CuCl as additive (Table 1, entry 2). Further screening of additives revealed that this reaction proceeded more efficiently when a catalytic amount of Cu(OTf)2 was used, affording 3a in 95% yield as the sole product (Table 1, entries 3–6). Next, different TEMPO oxoammonium salts were investigated (Table 1, entries 7–9), and the yield of product 3a increased to 98% when TEMPO+BF4− was used as oxidant. Notably, decreasing the amount of Cu(OTf)2 to 0.005 equivalent had no effect on the reactivity of the reaction (Table 1, entry 10). Moreover, under the optimized conditions, the dimer 6a was obtained in 98% yield when no extra nucleophile was added (entry 11). Finally, the optimal conditions were established as: TEMPO+BF4− (1.0 eq)/Cu(OTf)2 (0.005 eq)/THF.
With the optimized conditions in hand, the scope with respect to both indoles (1) and dicarbonyl compounds (2) was explored (Figure 3). In general, structurally and electronically varied 2-phenyl indoles were compatible with the reaction conditions, affording the desired 2,2-disubstituted indolin-3-ones in excellent yields (3a–3f). Notably, when the reaction of 1a and 2a was performed in gram scale, the desired product was obtained in 96% yield. Moreover, 2-aryl indoles bearing either electron-donating or withdrawing functional groups on the aryl moiety participated in the reactions smoothly, giving indolin-3-ones 3g–3j in high yields (83–99%). Electron-rich 2-aryl indoles like 1h and 1j afforded comparable results to that of 2-phenyl indole, while electron-deficient indoles like 1g and 1i gave slightly reduced yields. Excitingly, 2-methyl indole was also tolerated with the reaction conditions in good yield, which provided a straightforward approach to 2,2-dialkyl substituted indolin-3-ones. Furthermore, a variety of commercially available malonates, such as dimethyl, diisopropyl, ditert-butyl, dibutyl, and dibenzyl malonates, smoothly participated in the reaction, giving 2,2-disubstituted indolin-3-ones 3l–3p in 95–99% yields. Additionally, acetylacetone was also a suitable substrate for the reaction, with only a moderately reduced yield (3q, 80%).
Bisindole scaffolds exist in a number of bioactive natural products [42,86,87,88]. For example, isatisine A from the leaves of Isatis indigotica showed anti-HIV activity [89], while halichrome A from a metagenomic library derived from the marine sponge Halichondria okadai exhibited cytotoxicity against B16 melanoma cells [89]. Herein, the cross-dehydrogenative coupling of C-2 substituted indoles (1) with dissimilar indole nucleophiles (4) was next explored (Figure 4). When the reaction was conducted at 0 °C, a similar scope of C-2 substituted indoles as for the aforementioned dicarbonyls were tried, providing the corresponding 2,2-disusbtituted indolin-3-ones in excellent yields. The reaction of 2-phenyl indole bearing an electron-withdrawing group on indole ring gave the indolin-3-one 5b with a slightly decreased yield. Moreover, a number of 2-alkyl indoles were also suitable for the reaction with very decent product yields (5h–5k) and displayed excellent regio-selectivity, as no benzylic oxidation products were observed. It is worth noting that natural product halichrome A (5i) was successfully synthesized in 92% yield using the current method. A broad range of electronically varied indoles with different substitution patterns were also found to be appropriate nucleophiles for this process, affording the expected products 5l–5q in excellent yields. However, when C-3 substituted indoles such as 3-methylindole, melatonine, and tryptamine derivative were subjected to the reaction, the expected 2,2′-bisindolin-3-ones 5r–5t were obtained in low yields. Excitingly, MeOH as an additive proved to be beneficial and enhanced the reactivity of the reaction, and satisfying yields (90–92%) of coupling products were achieved [89,90,91,92,93].
The oxidative dimerization of 1a was realized in 96% or 98% yield without any additive and extra nucleophiles using TEMPO+ClO4− or TEMPO+BF4− as oxidant (Table 1, entries 1 and 11). Therefore, the scope of dimerization of C-2 substituted indoles was subsequently investigated (Figure 5). Structurally and electronically varied C-2 substituted indoles proved to be effective substrates, delivering the dimers 6a–6h in excellent yields. Next, the universality of the developed method was further explored in the formation of oxidative trimers (2,2-bis(indol-3-yl)indolin-3-ones). The oxidative process exhibited excellent regio-selectivity and produced the desired trimeric products as single isomers without any 3,3-disubstituted indolin-3-ones generated, and proceeded with moderate yields. Interestingly, yields of the trimers increased remarkably to 80–90% when the reactions were conducted with excess oxidant.
The successful oxidative cross-dehydrogenative coupling of indoles with 1,3-dicarbonyl compounds and indole nucleophiles prompted us to further explore the reaction of indoles with other diverse C-H nucleophiles under the developed conditions (Figure 6). Delightedly, the CDC reactions of 2-phenyl indole 1a with a number of C-H nucleophiles including pyrrole, thiophene, acetaldehyde and acetone, went smoothly to give the desired products 8–12 in good yields. It was noteworthy that C-3 position was the major reactive nucleophilic site of N-methyl pyrrole. However, π-rich arenes did not afford the desired products.

3. Materials and Methods

3.1. Materials

THF (Tianjin Fuyu Fine Chemical Co. Ltd., Tianjin, China) was freshly distilled over Na. Other reagents and solvents (J&K Inc. Ltd., Shanghai, China) were used as commercially available products without further purification unless specified. Proton (1H) and carbon (13C) nuclear magnetic resonance (NMR) spectra were recorded on a Bruker AVANCE DRX600 NMR spectrometer (Bruker BioSpin AG, Fällanden, Switzerland). The chemical shifts were given in parts per million (ppm) on the delta (δ) scale, and the residual solvent peaks were used as references as follows: CDCl3 δH 7.26, δC 77.16 ppm; acetone-d6 δH 2.05, δC 29.84 ppm; DMSO-d6 δH 2.50, δC 39.52 ppm. Analytical TLC was performed on precoated silica gel GF254 plates (Qingdao Haiyang Chemical Co. Ltd., Qingdao, China). Column chromatography was carried out on silica gel (200–300 mesh, Qingdao Haiyang Chemical Co. Ltd., Qingdao, China). ESIMS analyses were performed on an Agilent 1260-6460 Triple Quad LC-MS spectrometer (Agilent Technologies Inc., Waldbronn, Germany). HR-ESIMS were carried out on an Agilent 6520 Q-TOF MS spectrometer (Agilent Technologies Inc., Waldbronn, Germany).

3.2. General Procedure for the Oxidative Dearomative Cross-Dehydrogenative Coupling Reactions

General procedure A: To a solution of 1 (0.1 mmol), 2 (0.2 mmol) and Cu(OTf)2 (0.005 eq.) in THF (1.0 mL) was added TEMPO+BF4− (0.1 mmol) at room temperature. The mixture was further stirred until the disappearance of starting indole by TLC analysis at room temperature. Then, the solvent was removed, and the residue was purified by flash chromatography using acetone-petroleum ether as eluent to afford the desired product.
General procedure B: To a solution of 1 (0.1 mmol) and 4 (0.2 mmol) in THF (1.0 mL) was added TEMPO+BF4− (0.1 mmol) at 0 °C. The mixture was further stirred until the disappearance of starting material 1 by TLC analysis at 0 °C. The solvent was removed and the residue was purified by flash chromatography using acetone-petroleum ether as eluent to afford the desired product.
General procedure C: To a solution of 1 (0.1 mmol) and MeOH (0.5 mmol) in THF (1.0 mL) was added TEMPO+BF4− (0.1 mmol) at 0 °C. The mixture was stirred at 0 °C until the disappearance of 1. Nucleophiles 4r–4t (0.2 mmol) were added to the mixture and the reaction was further stirred until the disappearance of intermediates by TLC analysis at 0 °C. Then, the solvent was removed and the residue was purified by flash chromatography using acetone-petroleum ether as eluent to afford the desired product.
General procedure D: To a solution of C2-substituted indole (0.2 mmol) or indole (0.3 mmol) in THF (1.0 mL) was added TEMPO+BF4− (0.1 mmol). The mixture was stirred at room temperature for 6 h. The solvent was removed and the residue was purified by flash chromatography using acetone-petroleum ether as eluent to afford the desired product.
For original 1H and 13C NMR spectra of all synthesized compounds please see the Supplementary Materials.
Diethyl 2-(3-oxo-2-phenylindolin-2-yl)malonate (3a). According to procedure A, 3a was obtained as a yellow solid in 98% yield (36.0 mg; flash chromatographic condition: petroleum ether-acetone 90:10). 1H NMR (600 MHz, CDCl3) δ 7.56 (d, J = 7.7 Hz, 1H), 7.54–7.51 (m, 2H), 7.49–7.45 (m, 1H), 7.30 (t, J = 7.6 Hz, 2H), 7.25 (t, J = 7.3 Hz, 1H), 6.97 (d, J = 8.2 Hz, 1H), 6.81 (t, J = 7.4 Hz, 1H), 6.09 (s, 1H), 4.72 (s, 1H), 4.10–3.99 (m, 3H), 3.91 (dq, J = 10.8, 7.1 Hz, 1H), 1.02 (t, J = 7.1 Hz, 3H), 0.85 (t, J = 7.2 Hz, 3H); 13C NMR (151 MHz, CDCl3) δ 198.1 (C=O), 167.9 (C=O), 166.4 (C=O), 160.2 (Cq), 137.4 (CH), 136.9 (Cq), 128.9 (CH, 2C), 128.2 (CH), 125.5 (CH), 125.4 (CH, 2C), 119.6 (Cq), 119.2 (CH), 111.5 (CH), 70.4 (Cq), 62.0 (CH2), 61.7 (CH2), 58.8 (CH), 13.8 (CH3), 13.4 (CH3); HR-ESIMS m/z calcd for C21H22NO5 [M + H]+ 368.1492, found 368.1494.
Diethyl 2-(5-chloro-3-oxo-2-phenylindolin-2-yl)malonate (3b). According to procedure A, 3b was obtained as a yellow solid in 90% yield (36.1 mg; flash chromatographic condition: petroleum ether-acetone 90:10). 1H NMR (600 MHz, CDCl3) δ 7.53 (d, J = 2.2 Hz, 1H), 7.50 (t, J = 1.7 Hz, 1H), 7.49 (t, J = 1.7 Hz, 1H), 7.42 (dd, J = 8.7, 2.2 Hz, 1H), 7.33–7.30 (m, 2H), 7.27 (dt, J = 14.4, 1.1 Hz, 1H), 6.94 (d, J = 8.6 Hz, 1H), 6.13 (s, 1H), 4.70 (s, 1H), 4.09–4.01 (m, 3H), 3.96 (dq, J = 10.8, 7.1 Hz, 1H), 1.02 (t, J = 7.1 Hz, 3H), 0.95 (t, J = 7.1 Hz, 3H); 13C NMR (151 MHz, CDCl3) δ 196.0 (C=O), 166.8 (C=O), 165.2 (C=O), 157.4 (Cq), 136.3 (CH), 135.4 (Cq), 128.1 (CH, 2C), 127.5 (CH), 124.4 (CH, 2C), 123.8 (CH), 123.4 (Cq), 119.8 (Cq), 111.7 (CH), 70.0 (Cq), 61.2 (CH2), 60.9 (CH2), 57.8 (CH), 12.9 (CH3), 12.6 (CH3); HR-ESIMS m/z calcd for C21H21ClNO5 [M + H]+ 402.1103, found 402.1103.
Diethyl 2-(5-methyl-3-oxo-2-phenylindolin-2-yl)malonate (3c). According to procedure A, 3c was obtained as a yellow solid in 95% yield (36.2 mg; flash chromatographic condition: petroleum ether-acetone 90:10). 1H NMR (600 MHz, CDCl3) δ 7.52–7.48 (m, 2H), 7.36 (s, 1H), 7.32–7.28 (m, 3H), 7.25 (d, J = 7.3 Hz, 1H), 6.90 (d, J = 8.3 Hz, 1H), 5.92 (s, 1H), 4.71 (s, 1H), 4.10–3.99 (m, 3H), 3.92 (dq, J = 10.8, 7.1 Hz, 1H), 2.27 (s, 3H), 1.02 (t, J = 7.1 Hz, 3H), 0.89 (t, J = 7.1 Hz, 3H); 13C NMR (151 MHz, CDCl3) δ 198.2 (C=O), 167.9 (C=O), 166.5 (C=O), 158.7 (Cq), 138.8 (CH), 137.2 (Cq), 128.9 (CH, 2C), 128.8 (Cq), 128.1 (CH), 125.4 (CH, 2C), 124.9 (CH), 119.8 (Cq), 111.5 (CH), 70.8 (Cq), 62.0 (CH2), 61.7 (CH2), 58.9 (CH), 20.6 (CH3), 13.9 (CH3), 13.5 (CH3); HR-ESIMS m/z calcd for C22H24NO5 [M + H]+ 382.1649, found 382.1650.
Diethyl 2-(5-methoxy-3-oxo-2-phenylindolin-2-yl)malonate (3d). According to procedure A, 3d was obtained as a yellow solid in 98% yield (38.9 mg; flash chromatographic condition: petroleum ether-acetone 90:10). 1H NMR (600 MHz, CDCl3) δ 7.52–7.48 (m, 2H), 7.36 (s, 1H), 7.32–7.28 (m, 3H), 7.25 (d, J = 7.3 Hz, 1H), 6.90 (d, J = 8.3 Hz, 1H), 5.92 (s, 1H), 4.71 (s, 1H), 4.10–3.99 (m, 3H), 3.92 (dq, J = 10.8, 7.1 Hz, 1H), 2.27 (s, 3H), 1.02 (t, J = 7.1 Hz, 3H), 0.89 (t, J = 7.1 Hz, 3H); 13C NMR (151 MHz, CDCl3) δ 198.1 (C=O), 167.6 (C=O), 166.2 (C=O), 155.8 (Cq), 153.4 (Cq), 136.9 (Cq), 128.7 (CH, 2C), 127.9 (CH), 127.6 (CH), 125.2 (CH, 2C), 119.6 (Cq), 112.9 (CH), 105.3 (CH), 71.1 (Cq), 61.8 (CH2), 61.5 (CH2), 58.7 (CH3), 55.6 (CH), 13.6 (CH3), 13.4 (CH3); HR-ESIMS m/z calcd for C22H24NO6 [M + H]+ 398.1598, found 398.1600.
Diethyl 2-(6-methyl-3-oxo-2-phenylindolin-2-yl)malonate (3e). According to procedure A, 3e was obtained as a yellow solid in 94% yield (35.8 mg; flash chromatographic condition: petroleum ether-acetone 90:10). 1H NMR (600 MHz, CDCl3) δ 7.51 (d, J = 7.6 Hz, 2H), 7.45 (d, J = 7.9 Hz, 1H), 7.29 (t, J = 7.6 Hz, 2H), 7.24 (t, J = 7.3 Hz, 1H), 6.78 (s, 1H), 6.64 (d, J = 7.9 Hz, 1H), 6.00 (s, 1H), 4.70 (s, 1H), 4.09–3.98 (m, 3H), 3.92 (dq, J = 10.8, 7.1 Hz, 1H), 2.38 (s, 3H), 1.02 (t, J = 7.1 Hz, 3H), 0.89 (t, J = 7.1 Hz, 3H); 13C NMR (151 MHz, CDCl3) δ 197.4 (C=O), 167.9 (C=O), 166.4 (C=O), 160.7 (Cq), 149.1 (Cq), 137.3 (Cq), 128.9 (CH, 2C), 128.1 (CH), 125.4 (CH, 2C), 125.3 (CH), 121.0 (CH), 117.4 (Cq), 111.6 (CH), 70.6 (Cq), 62.0 (CH2), 61.7 (CH2), 58.7 (CH), 22.6 (CH3), 13.8 (CH3), 13.5 (CH3); HR-ESIMS m/z calcd for C22H24NO5 [M + H]+ 382.1649, found 382.1648.
Diethyl 2-(7-methyl-3-oxo-2-phenylindolin-2-yl)malonate (3f). According to procedure A, 3f was obtained as a yellow solid in 91% yield (34.6 mg; flash chromatographic condition: petroleum ether-acetone 90:10). 1H NMR (600 MHz, CDCl3) δ 7.51 (d, J = 7.5 Hz, 2H), 7.43 (d, J = 7.7 Hz, 1H), 7.34–7.29 (m, 3H), 7.25 (t, J = 7.3 Hz, 1H), 6.76 (t, J = 7.4 Hz, 1H), 5.87 (s, 1H), 4.72 (s, 1H), 4.04 (m, 3H), 3.88 (dq, J = 10.7, 7.1 Hz, 1H), 2.35 (s, 3H), 1.05 (t, J = 7.1 Hz, 3H), 0.84 (t, J = 7.1 Hz, 3H); 13C NMR (151 MHz, CDCl3) δ 198.4 (C=O), 168.0 (C=O), 166.3 (C=O), 159.4 (Cq), 137.4 (CH), 137.1 (Cq), 128.9 (CH, 2C), 128.2 (CH), 125.4 (CH, 2C), 122.9 (CH), 120.7 (Cq), 119.4 (CH), 119.1 (Cq), 70.6 (Cq), 62.0 (CH2), 61.8 (CH2), 58.8 (CH), 15.9 (CH3), 13.9 (CH3), 13.4 (CH3); HR-ESIMS m/z calcd for C22H24NO5 [M + H]+ 382.1649, found 382.1649.
Diethyl 2-(2-(4-fluorophenyl)-3-oxoindolin-2-yl)malonate (3g). According to procedure A, 3g was obtained as a yellow solid in 90% yield (34,6 mg; flash chromatographic condition: petroleum ether-acetone 90:10). 1H NMR (600 MHz, CDCl3) δ 7.57 (d, J = 7.7 Hz, 1H), 7.56–7.52 (m, 2H), 7.50–7.46 (m, 1H), 7.03–6.95 (m, 3H), 6.83 (t, J = 7.4 Hz, 1H), 6.10 (s, 1H), 4.64 (s, 1H), 4.12–3.97 (m, 3H), 3.91 (dq, J = 10.8, 7.1 Hz, 1H), 1.06 (t, J = 7.1 Hz, 3H), 0.86 (t, J = 7.1 Hz, 4H); 13C NMR (151 MHz, CDCl3) δ 198.1 (C=O), 167.8 (C=O), 166.1 (C=O), 163.6 (Cq), 161.9 (Cq), 160.1 (Cq), 137.6 (CH), 132.8 (Cq), 132.8 (Cq), 127.5 (CH, 2C), 127.4 (CH, 2C), 125.6 (CH), 119.6 (Cq), 119.4 (CH), 115.9 (CH, 2C), 115.8 (CH, 2C), 111.6 (CH), 69.8 (Cq), 62.2 (CH2), 61.9 (CH2), 58.9 (CH), 13.9 (CH3), 13.4 (CH3); HR-ESIMS m/z calcd for C21H21FNO5 [M + H]+ 386.1398, found 386.1402.
Diethyl 2-(3-oxo-2-(p-tolyl)indolin-2-yl)malonate (3h). According to procedure A, 3h was obtained as a yellow solid in 99% yield (37.7 mg; flash chromatographic condition: petroleum ether-acetone 90:10). 1H NMR (600 MHz, CDCl3) δ 7.56 (d, J = 7.6 Hz, 1H), 7.46 (t, J = 7.6 Hz, 1H), 7.38 (d, J = 8.2 Hz, 2H), 7.11 (d, J = 8.1 Hz, 2H), 6.96 (d, J = 8.2 Hz, 1H), 6.80 (t, J = 7.4 Hz, 1H), 6.03 (s, 1H), 4.70 (s, 1H), 4.12–3.98 (m, 3H), 3.90 (dq, J = 10.8, 7.1 Hz, 1H), 2.28 (s, 3H), 1.06 (t, J = 7.1 Hz, 3H), 0.85 (t, J = 7.1 Hz, 3H); 13C NMR (151 MHz, CDCl3) δ 198.2 (C=O), 167.9 (C=O), 166.5 (C=O), 160.2 (Cq), 137.9 (Cq), 137.3 (CH), 133.9 (Cq), 129.7 (CH, 2C), 125.6 (CH), 125.2 (CH, 2C), 119.7 (Cq), 119.2 (CH), 111.5 (CH), 70.3 (Cq), 62.0 (CH2), 61.7 (CH2), 58.7 (CH), 21.0 (CH3), 13.9 (CH3), 13.4 (CH3); HR-ESIMS m/z calcd for C22H24NO5 [M + H]+ 382.1649, found 382.1651.
Diethyl 2-(3-oxo-2-(4-(trifluoromethoxy)phenyl)indolin-2-yl)malonate (3i). According to procedure A, 3i was obtained as a yellow solid in 83% yield (37.4 mg; flash chromatographic condition: petroleum ether-acetone 90:10). 1H NMR (600 MHz, CDCl3) δ 7.63–7.60 (m, 2H), 7.58 (d, J = 7.7 Hz, 1H), 7.51–7.47 (m, 1H), 7.16 (d, J = 8.3 Hz, 2H), 6.98 (d, J = 8.2 Hz, 1H), 6.84 (t, J = 7.4 Hz, 1H), 6.11 (s, 1H), 4.64 (s, 1H), 4.09–4.03 (m, 2H), 4.00 (ddd, J = 14.3, 9.0, 5.4 Hz, 1H), 3.91 (dq, J = 10.8, 7.1 Hz, 1H), 1.03 (t, J = 7.1 Hz, 3H), 0.87 (t, J = 7.1 Hz, 3H); 13C NMR (151 MHz, CDCl3) δ 197.9 (C=O), 167.8 (C=O), 165.9 (C=O), 160.1 (Cq), 149.2 (Cq) 137.7 (CH), 135.9 (Cq), 127.3 (CH, 2C), 125.6 (CH), 121.3 (Cq), 121.2 (CH, 2C), 119.6 (Cq), 119.5 (CH), 119.5 (Cq), 111.7 (CH), 69.8 (Cq), 62.2 (CH2), 61.9 (CH2), 58.9 (CH), 13.8 (CH3), 13.5 (CH3); HR-ESIMS m/z calcd for C22H21F3NO6 [M + H]+ 452.1315, found 452.1314.
Diethyl 2-(2-(3-methoxyphenyl)-3-oxoindolin-2-yl)malonate (3j). According to procedure A, 3j was obtained as a yellow solid in 99% yield (39.3 mg; flash chromatographic condition: petroleum ether-acetone 90:10). 1H NMR (600 MHz, CDCl3) δ 7.56 (d, J = 7.7 Hz, 1H), 7.47 (ddd, J = 8.3, 7.2, 1.3 Hz, 1H), 7.22 (t, J = 8.0 Hz, 1H), 7.09 (ddd, J = 7.9, 1.8, 0.8 Hz, 1H), 7.07–7.05 (m, 1H), 6.96 (d, J = 8.2 Hz, 1H), 6.83–6.77 (m, 2H), 6.04 (s, 1H), 4.70 (s, 1H), 4.13–3.98 (m, 3H), 3.90 (dq, J = 10.7, 7.2 Hz, 1H), 3.77 (s, 3H), 1.06 (t, J = 7.1 Hz, 3H), 0.85 (t, J = 7.1 Hz, 3H); 13C NMR (151 MHz, CDCl3) δ 197.9 (C=O), 167.9 (C=O), 166.4 (C=O), 160.2 (Cq), 159.9 (Cq), 138.6 (Cq), 137.4 (CH), 129.9 (CH), 125.5 (CH), 119.6 (Cq), 119.3 (CH), 117.7 (CH), 113.3 (CH), 111.6 (CH), 111.5 (CH), 70.3 (Cq), 62.0 (CH2), 61.8 (CH2), 58.7 (CH3), 55.3 (CH), 13.9 (CH3), 13.4 (CH3); HR-ESIMS m/z calcd for C22H24NO6 [M + H]+ 398.1598, found 398.1599.
Diethyl 2-(2-methyl-3-oxoindolin-2-yl)malonate (3k). According to procedure A, 3k was obtained as a yellow solid in 84% yield (25.6 mg; flash chromatographic condition: petroleum ether-acetone 90:10). 1H NMR (600 MHz, CDCl3) δ 7.63 (d, J = 7.7 Hz, 1H), 7.45–7.41 (m, 1H), 6.85–6.79 (m, 2H), 5.45 (s, 1H), 4.36–4.27 (m, 2H), 3.98 (s, 1H), 3.97–3.93 (m, 1H), 3.89–3.83 (m, 1H), 1.35 (s, 3H), 1.33 (t, J = 7.1 Hz, 3H), 0.85 (t, J = 7.1 Hz, 3H); 13C NMR (151 MHz, CDCl3) δ 201.6 (C=O), 168.4 (C=O), 166.5 (C=O), 159.8 (Cq), 137.2 (CH), 125.0 (CH), 120.1 (Cq), 119.0 (CH), 112.3 (CH), 65.3 (Cq), 61.9 (CH2), 61.9 (CH2), 57.8 (CH), 22.3 (CH3), 14.2 (CH3), 13.4 (CH3); HR-ESIMS m/z calcd for C16H20NO5 [M + H]+ 306.1336, found 306.1335.
Dimethyl 2-(3-oxo-2-phenylindolin-2-yl)malonate (3l). According to procedure A, 3l was obtained as a yellow solid in 97% yield (32.8 mg; flash chromatographic condition: petroleum ether-acetone 90:10). 1H NMR (600 MHz, CDCl3) δ 7.57 (d, J = 7.7 Hz, 1H), 7.53–7.50 (m, 2H), 7.50–7.46 (m, 1H), 7.31 (t, J = 7.6 Hz, 2H), 7.26 (dd, J = 7.9, 5.9 Hz, 1H), 6.98 (d, J = 8.2 Hz, 1H), 6.82 (t, J = 7.4 Hz, 1H), 6.08 (s, 1H), 4.76 (s, 1H), 3.58 (s, 3H), 3.49 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 198.1 (C=O), 168.4 (C=O), 166.6 (C=O), 160.2 (Cq), 137.5 (CH), 136.8 (Cq), 129.0 (CH, 2C), 128.3 (CH), 125.6 (CH), 125.3 (CH, 2C), 119.4 (Cq), 119.4 (CH), 111.6 (CH), 70.4 (Cq), 58.6 (CH), 52.8 (CH3, 2C); HR-ESIMS m/z calcd for C19H18NO5 [M + H]+ 340.1179, found 340.1181.
Diisopropyl 2-(3-oxo-2-phenylindolin-2-yl)malonate (3m). According to procedure A, 3m was obtained as a yellow solid in 95% yield (37.5 mg; flash chromatographic condition: petroleum ether-acetone 90:10). 1H NMR (600 MHz, CDCl3) δ 7.56 (d, J = 7.7 Hz, 1H), 7.53–7.50 (m, 2H), 7.46 (t, J = 7.7 Hz, 1H), 7.29 (t, J = 7.6 Hz, 2H), 7.24 (t, J = 7.3 Hz, 1H), 6.96 (d, J = 8.2 Hz, 1H), 6.80 (t, J = 7.4 Hz, 1H), 6.09 (s, 1H), 4.89–4.82 (m, 2H), 4.66 (s, 1H), 1.09 (d, J = 6.3 Hz, 3H), 1.06 (d, J = 6.3 Hz, 3H), 0.98 (d, J = 6.3 Hz, 3H), 0.72 (d, J = 6.3 Hz, 3H); 13C NMR (151 MHz, CDCl3) δ 198.0 (C=O), 167.5 (C=O), 165.9 (C=O), 160.2 (Cq), 137.3 (CH), 137.2 (Cq), 128.9 (CH, 2C), 128.1 (CH), 125.5 (CH), 125.4 (CH, 2C), 119.8 (Cq), 119.2 (CH), 111.5 (CH), 70.4 (CH), 70.1 (CH), 69.4 (Cq), 59.1 (CH), 21.5 (CH3), 21.4 (CH3), 21.3 (CH3), 20.7 (CH3); HR-ESIMS m/z calcd for C23H26NO5 [M + H]+ 396.1805, found 396.1803.
Di-tert-butyl 2-(3-oxo-2-phenylindolin-2-yl)malonate (3n). According to procedure A, 3n was obtained as a yellow solid in 96% yield (32.5 mg; flash chromatographic condition: petroleum ether-acetone 90:10). 1H NMR (600 MHz, CDCl3) δ 7.56 (d, J = 7.6 Hz, 1H), 7.53 (d, J = 7.6 Hz, 2H), 7.48 (ddd, J = 8.3, 7.2, 1.3 Hz, 1H), 7.31 (t, J = 7.6 Hz, 2H), 7.26–7.23 (m, 1H), 6.96 (d, J = 8.2 Hz, 1H), 6.81 (t, J = 7.3 Hz, 1H), 6.07 (s, 1H), 4.56 (s, 1H), 1.23 (s, 9H), 1.14 (s, 9H); 13C NMR (151 MHz, CDCl3) δ 197.9 (C=O), 167.0 (C=O), 165.6 (C=O), 160.1 (Cq), 137.4 (Cq), 137.2 (CH), 128.6 (2C, CH), 127.8 (CH), 125.5 (CH), 125.4 (2C, CH), 119.6 (Cq), 118.9 (CH), 111.2 (CH), 83.1 (Cq), 82.3(Cq), 70.5(Cq), 60.4 (CH), 27.5 (CH3, 3C), 27.4 (CH3, 3C); HR-ESIMS m/z calcd for C25H30NO5 [M + H]+ 424.2118, found 424.2122.
Dibutyl 2-(3-oxo-2-phenylindolin-2-yl)malonate (3o). According to procedure A, 3o was obtained as a yellow solid in 99% yield (41.9 mg; flash chromatographic condition: petroleum ether-acetone 90:10). 1H NMR (600 MHz, CDCl3) δ 7.55 (d, J = 7.7 Hz, 1H), 7.53 (dd, J = 8.2, 0.9 Hz, 2H), 7.48–7.45 (m, 1H), 7.30 (t, J = 7.6 Hz, 2H), 7.25 (t, J = 7.3 Hz, 1H), 6.97 (d, J = 8.2 Hz, 1H), 6.81 (t, J = 7.4 Hz, 1H), 6.09 (s, 1H), 4.74 (s, 1H), 4.02–3.96 (m, 2H), 3.96–3.87 (m, 2H), 1.45–1.35 (m, 2H), 1.27–1.10 (m, 6H), 0.83 (t, J = 7.4 Hz, 3H), 0.78 (t, J = 7.2 Hz, 3H); 13C NMR (151 MHz, CDCl3) δ 198.0 (C=O), 168.1 (C=O), 166.5 (C=O), 160.2 (Cq), 137.4 (CH), 137.0 (Cq), 128.9 (CH, 2C), 128.2 (CH), 125.6 (CH), 125.4 (CH, 2C), 119.6 (Cq), 119.2 (CH), 111.6 (CH), 70.3 (Cq), 65.9 (CH2), 65.5 (CH2), 58.8 (CH), 30.4 (CH2), 30.1 (CH2), 18.9 (CH2, 2C), 13.7 (CH3), 13.6 (CH3); HR-ESIMS m/z calcd for C25H30NO5 [M + H]+ 424.2118, found 424.2120.
Dibenzyl 2-(3-oxo-2-phenylindolin-2-yl)malonate (3p). According to procedure A, 3p was obtained as a yellow solid in 99% yield (48.6 mg; flash chromatographic condition: petroleum ether-acetone 90:10). 1H NMR (600 MHz, CDCl3) δ 7.46 (dd, J = 7.8, 1.6 Hz, 2H), 7.43 (d, J = 7.7 Hz, 1H), 7.40 (ddd, J = 8.3, 7.2, 1.3 Hz, 1H), 7.29–7.18 (m, 9H), 7.01 (t, J = 6.9 Hz, 4H), 6.85 (d, J = 8.2 Hz, 1H), 6.75–6.71 (m, 1H), 6.01 (s, 1H), 4.97 (s, 2H), 4.93 (d, J = 12.2 Hz, 1H), 4.89 (d, J = 12.2 Hz, 1H), 4.84 (s, 1H); 13C NMR (151 MHz, CDCl3) δ 197.7 (C=O), 167.8 (C=O), 166.1 (C=O), 160.0 (Cq), 137.3 (CH), 136.8 (Cq), 134.9 (Cq), 134.6 (Cq), 129.0 (CH, 2C), 128.6 (CH, 2C), 128.5 (CH, 2C), 128.4 (CH), 128.3 (CH, 2C), 128.3 (CH), 128.2 (CH), 128.2 (CH, 2C), 125.6 (CH), 125.4 (CH, 2C), 119.4 (Cq), 119.3 (CH), 111.5 (CH), 70.4 (Cq), 67.8 (CH2), 67.5 (CH2), 58.8 (CH); HR-ESIMS m/z calcd for C31H26NO5 [M + H]+ 492.1805, found 492.1807.
3-(3-oxo-2-phenylindolin-2-yl)pentane-2,4-dione (3q). According to procedure A, 3q was obtained as a yellow solid in 80% yield (24.6 mg; flash chromatographic condition: petroleum ether-acetone 90:10). 1H NMR (600 MHz, CDCl3) δ 7.61 (d, J = 7.4 Hz, 2H), 7.53 (d, J = 7.7 Hz, 1H), 7.48 (ddd, J = 8.3, 7.2, 1.2 Hz, 1H), 7.32 (t, J = 7.7 Hz, 2H), 7.25 (d, J = 7.3 Hz, 1H), 6.99 (d, J = 8.3 Hz, 1H), 6.80 (t, J = 7.2 Hz, 1H), 6.28 (s, 1H), 5.08 (s, 1H), 2.14 (s, 3H), 2.05 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 203.6 (C=O), 200.1 (C=O), 199.6 (C=O), 160.8 (Cq), 138.1 (CH), 137.5 (Cq), 129.0 (CH, 2C), 128.2 (CH), 125.5 (CH, 2C), 125.4 (CH), 119.4 (CH), 119.2 (Cq), 112.3 (CH), 71.2 (Cq), 71.1 (CH), 33.1 (CH3), 31.3 (CH3); HR-ESIMS m/z calcd for C19H18NO3 [M + H]+ 308.1281, found 308.1280.
2-(1H-Indol-3-yl)-2-phenylindolin-3-one (5a). According to procedure B, 5a was obtained as a yellow solid in 98% yield (31.8 mg; flash chromatographic condition: petroleum ether-acetone 85:15). 1H NMR (600 MHz, acetone-d6) δ 10.28 (s, 1H), 7.61 (d, J = 7.6 Hz, 2H), 7.57 (d, J = 7.7 Hz, 1H), 7.53 (ddd, J = 8.4, 7.1, 1.4 Hz, 1H), 7.43 (d, J = 8.2 Hz, 1H), 7.36–7.23 (m, 4H), 7.21 (s, 1H), 7.16 (d, J = 8.0 Hz, 1H), 7.08 (t, J = 9.0 Hz, 2H), 6.90–6.79 (m, 2H); 13C NMR (151 MHz, acetone-d6) δ 200.9(C=O), 161.9(Cq), 141.4(Cq), 138.3(CH), 138.2(Cq), 128.9(CH, 2C), 128.2(CH), 127.7(CH, 2C), 126.8(Cq), 125.5(CH), 124.9(CH), 122.5(CH), 121.0(CH), 119.8(CH), 119.6(Cq), 119.0(CH), 116.3(Cq), 113.3(CH), 112.6(CH), 71.9(Cq); HR-ESIMS m/z calcd for C22H17N2O [M + H]+ 325.1335, found 325.1337.
5-Chloro-2-(1H-indol-3-yl)-2-phenylindolin-3-one (5b). According to procedure B, 5b was obtained as a yellow solid in 90% yield (32.3 mg; flash chromatographic condition: petroleum ether-acetone 85:15). 1H NMR (600 MHz, CDCl3) δ 8.25 (s, 1H), 7.64 (d, J = 2.2 Hz, 1H), 7.57–7.51 (m, 2H), 7.44 (dd, J = 8.7, 2.2 Hz, 1H), 7.36 (d, J = 8.2 Hz, 1H), 7.33–7.28 (m, 3H), 7.18 (t, J = 7.6 Hz, 1H), 7.13 (d, J = 8.0 Hz, 1H), 7.09 (d, J = 2.5 Hz, 1H), 6.99 (t, J = 7.6 Hz, 1H), 6.86 (d, J = 8.7 Hz, 1H), 5.43 (s, 1H); 13C NMR (151 MHz, CDCl3) δ 199.6 (C=O), 158.9 (Cq), 139.1 (Cq), 137.6 (CH), 137.1 (Cq), 128.7 (CH, 2C), 128.1 (CH), 126.8 (CH, 2C), 125.6 (Cq), 124.9 (CH), 124.9 (Cq), 123.9 (CH), 122.8 (CH), 120.7 (Cq), 120.3 (CH), 119.7 (CH), 115.3 (Cq), 114.2 (CH), 111.9 (CH), 72.3 (Cq); HR-ESIMS m/z calcd for C22H16ClN2O [M + H]+ 359.0946, found 359.0950.
2-(1H-Indol-3-yl)-5-methyl-2-phenylindolin-3-one (5c). According to procedure B, 5c was obtained as a yellow solid in 95% yield (32.2 mg; flash chromatographic condition: petroleum ether-acetone 85:15). 1H NMR (600 MHz, CDCl3) δ 8.16 (s, 1H), 7.56 (dt, J = 3.8, 2.1 Hz, 2H), 7.50 (s, 1H), 7.38 (d, J = 8.2 Hz, 1H), 7.35 (dd, J = 8.3, 1.7 Hz, 1H), 7.32–7.27 (m, 3H), 7.20–7.15 (m, 3H), 6.99 (dd, J = 11.2, 4.0 Hz, 1H), 6.87 (d, J = 8.3 Hz, 1H), 5.23 (s, 1H), 2.33 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 200.9 (C=O), 159.2 (Cq), 139.8(Cq), 139.1 (CH), 137.0 (Cq), 129.4 (Cq), 128.5 (CH, 2C), 127.8 (CH), 126.9 (CH, 2C), 125.8 (Cq), 125.0 (CH), 123.9 (CH), 122.6 (CH), 120.1(CH), 119.9 (Cq), 119.9 (CH), 115.8 (Cq), 113.1 (CH), 111.8 (CH), 71.8 (Cq), 20.7 (CH3); HR-ESIMS m/z calcd for C23H19N2O [M + H]+ 339.1492, found 339.1495.
2-(1H-Indol-3-yl)-5-methoxy-2-phenylindolin-3-one (5d). According to procedure B, 5d was obtained as a yellow solid in 98% yield (34.6 mg; flash chromatographic condition: petroleum ether-acetone 85:15). 1H NMR (600 MHz, CDCl3) δ 8.27 (s, 1H), 7.56 (dd, J = 8.1, 1.7 Hz, 2H), 7.34 (d, J = 8.3 Hz, 1H), 7.32–7.24 (m, 3H), 7.21–7.09 (m, 5H), 6.97 (t, J = 7.5 Hz, 1H), 6.89 (d, J = 8.8 Hz, 1H), 5.13 (s, 1H), 3.77 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 201.2 (C=O), 156.6 (Cq), 154.0 (Cq), 139.8 (Cq), 137.0 (Cq), 128.5 (CH, 2C), 128.3 (CH), 127.8 (CH), 126.9 (CH, 2C), 125.7 (Cq), 123.8 (Cq), 122.6 (CH), 120.1 (CH), 120.0 (CH), 119.8(CH), 115.8 (Cq), 114.8 (CH), 111.8 (CH), 105.2 (CH), 72.4 (Cq), 55.9 (CH3); HR-ESIMS m/z calcd for C23H19N2O2 [M + H]+ 355.1441, found 355.1443.
2-(1H-Indol-3-yl)-6-methyl-2-phenylindolin-3-one (5e). According to procedure B, 5e was obtained as a yellow solid in 94% yield (31.8 mg; flash chromatographic condition: petroleum ether-acetone 85:15). 1H NMR (600 MHz, acetone-d6) δ 10.24 (s, 1H), 7.61–7.56 (m, 2H), 7.43 (d, J = 8.1 Hz, 1H), 7.41 (d, J = 8.2 Hz, 1H), 7.33–7.24 (m, 3H), 7.19–7.12 (m, 3H), 7.07 (ddd, J = 8.2, 7.0, 1.1 Hz, 1H), 6.89–6.81 (m, 2H), 6.65 (dd, J = 7.9, 1.1 Hz, 1H), 2.34 (s, 3H); 13C NMR (151 MHz, acetone-d6) δ 200.1 (C=O), 162.4 (Cq), 149.6 (Cq), 141.8 (Cq), 138.3 (Cq), 128.9 (CH, 2C), 128.2 (CH), 127.8 (CH, 2C), 126.9 (Cq), 125.4 (CH), 125.0 (CH), 122.5 (CH), 121,1 (CH), 120.9 (CH), 119.8 (CH), 117.5 (Cq), 116.7 (Cq), 113.2 (CH), 112.5 (CH), 72.2 (Cq), 22.5 (CH3); HR-ESIMS m/z calcd for C23H19N2O [M + H]+ 339.1492, found 339.1494.
2-(1H-Indol-3-yl)-7-methyl-2-phenylindolin-3-one (5f). According to procedure B, 5f was obtained as a yellow solid in 91% yield (30.8 mg; flash chromatographic condition: petroleum ether-acetone 85:15). 1H NMR (600 MHz, CDCl3) δ 8.19 (s, 1H), 7.62–7.53 (m, 3H), 7.38–7.25 (m, 5H), 7.21–7.13 (m, 3H), 6.99 (t, J = 7.5 Hz, 1H), 6.85 (t, J = 7.5 Hz, 1H), 5.12 (s, 1H), 2.27 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 201.1(C=O), 159.8 (Cq), 139.7 (Cq), 137.5 (CH), 137.0 (Cq), 128.5 (CH, 2C), 127.8 (CH), 126.9 (CH, 2C), 125.8 (Cq), 124.0 (CH), 123.0 (CH), 122.5 (CH), 122.1 (Cq), 120.1 (CH), 119.9 (CH), 119.9 (CH), 119.3 (Cq), 115.8 (Cq), 111.7 (CH), 71.4 (Cq), 15.9 (CH3); HR-ESIMS m/z calcd for C23H19N2O [M + H]+ 339.1492, found 339.1496.
2-(4-Fluorophenyl)-2-(1H-indol-3-yl)indolin-3-one (5g). According to procedure B, 5g was obtained as a yellow solid in 97% yield (33.2 mg; flash chromatographic condition: petroleum ether-acetone 85:15). 1H NMR (600 MHz, CDCl3) δ 8.29 (s, 1H), 7.70 (dd, J = 7.7, 1.3 Hz, 1H), 7.56–7.48 (m, 3H), 7.26 (s, 1H), 7.18 (ddd, J = 8.2, 7.0, 1.1 Hz, 1H), 7.16–7.09 (m, 2H), 7.03–6.94 (m, 3H), 6.94–6.88 (m, 2H), 5.37 (s, 1H); 13C NMR (151 MHz, CDCl3 ) δ 200.7 (C=O), 163.5 (Cq), 161.8 (Cq), 160.7 (Cq), 137.8 (CH), 137.1 (Cq), 135.4 (Cq), 135.4 (Cq), 128.8 (CH, 2C), 128.7 (CH, 2C), 125.7 (CH), 125.6 (Cq), 123.8 (CH), 122.8 (CH), 120.2 (CH), 120.0 (CH), 119.7 (CH), 119.6 (Cq), 115.5 (Cq), 115.4 (CH, 2C), 115.3 (CH, 2C), 113.2 (CH), 111.9 (CH), 70.9 (Cq); HR-ESIMS m/z calcd for C22H16FN2O [M + H]+ 343.1241, found 343.1238.
2-(1H-Indol-3-yl)-2-methylindolin-3-one (5h). According to procedure B, 5h was obtained as a yellow solid in 95% yield (24.9 mg; flash chromatographic condition: petroleum ether-acetone 85:15). 1H NMR (600 MHz, acetone-d6) δ 10.20 (s, 1H), 7.57–7.49 (m, 2H), 7.43–7.34 (m, 3H), 7.06 (ddd, J = 8.0, 6.9, 1.1 Hz, 1H), 7.00 (d, J = 8.1 Hz, 1H), 6.87 (t, J = 7.5 Hz, 1H), 6.84–6.75 (m, 2H), 1.75 (s, 3H); 13C NMR (151 MHz, acetone-d6) δ 203.6 (C=O), 161.5 (Cq), 138.2(Cq), 138.0 (CH), 126.3 (Cq), 125.3 (CH), 123.8 (CH), 122.2 (CH), 121.0 (CH), 119.9 (Cq), 119.6 (CH), 118.5 (CH), 116.4 (Cq), 113.1 (CH), 112.3 (CH), 66.4(Cq), 24.1 (CH3); HR-ESIMS m/z calcd for C17H15N2O [M + H]+ 263.1179, found 263.1176.
2-Ethyl-2-(1H-indol-3-yl)indolin-3-one (5i). According to procedure B, 5i was obtained as a yellow solid in 92% yield (25.3 mg; flash chromatographic condition: petroleum ether-acetone 85:15). 1H NMR (600 MHz, acetone-d6) δ 10.19 (s, 1H), 7.65 (d, J = 8.1 Hz, 1H), 7.55–7.45 (m, 2H), 7.41–7.33 (m, 2H), 7.11–6.99 (m, 2H), 6.92 (ddd, J = 8.1, 7.0, 1.1 Hz, 1H), 6.85 (s, 1H), 6.76 (ddd, J = 7.9, 7.1, 0.9 Hz, 1H), 2.35–2.30 (m, 1H), 2.26–2.21 (m, 1H), 0.89 (t, J = 7.4 Hz, 3H); 13C NMR (151 MHz, acetone-d6) δ 202.8 (C=O), 161.9 (Cq), 137.9 (Cq), 137.5 (CH), 126.0 (Cq), 124.6 (CH), 123.3 (CH), 121.9 (CH), 121.1 (CH), 120.6 (Cq), 119.3 (CH), 118.0 (CH), 115.2 (Cq), 112.4 (CH), 112.0 (CH), 70.1 (Cq), 30.5 (CH2), 8.1 (CH3); HR-ESIMS m/z calcd for C18H17N2O [M + H]+ 277.1335, found 277.1333.
2-(Cyclopropylmethyl)-2-(1H-indol-3-yl)indolin-3-one (5j). According to procedure B, 5j was obtained as a yellow solid in 90% yield (27.2 mg; flash chromatographic condition: petroleum ether-acetone 85:15). 1H NMR (600 MHz, CDCl3) δ 8.25 (s, 1H), 7.66 (dd, J = 7.7, 1.3 Hz, 1H), 7.55 (d, J = 8.1 Hz, 1H), 7.51 (ddd, J = 8.4, 7.1, 1.4 Hz, 1H), 7.32 (d, J = 8.2 Hz, 1H), 7.18–7.13 (m, 2H), 7.03 (ddd, J = 8.1, 7.0, 1.0 Hz, 1H), 6.94 (d, J = 8.2 Hz, 1H), 6.87–6.83 (m, 1H), 5.20 (s, 1H), 2.57 (dd, J = 14.0, 4.7 Hz, 1H), 1.82 (dd, J = 14.0, 8.7 Hz, 1H), 0.81–0.72 (m, 1H), 0.41–0.29 (m, 2H), 0.19 (dq, J = 9.6, 4.9 Hz, 1H), 0.13–0.07 (m, 1H); 13C NMR (151 MHz, CDCl3) δ 203.6 (C=O), 160.8 (Cq), 137.5 (CH), 137.0 (Cq), 125.3 (Cq), 125.2 (CH), 122.7 (CH), 122.4 (CH), 120.9 (Cq), 120.3 (CH), 120.0 (CH), 119.0 (CH), 115.2 (Cq), 112.3 (CH), 111.6 (CH), 70.0 (Cq), 42.3 (CH2), 6.1 (CH2), 5.3 (CH2), 4.0 (CH); HR-ESIMS m/z calcd for C20H19N2O [M + H]+ 303.1492, found 303.1493.
Ethyl 5-(2-(1H-indol-3-yl)-3-oxoindolin-2-yl)pentanoate (5k). According to procedure B, 5k was obtained as a yellow solid in 96% yield (36.1 mg; flash chromatographic condition: petroleum ether-acetone 85:15). 1H NMR (600 MHz, CDCl3) δ 8.49 (s, 1H), 7.65–7.61 (m, 1H), 7.49 (ddd, J = 8.3, 7.1, 1.4 Hz, 1H), 7.44 (d, J = 8.1 Hz, 1H), 7.30 (d, J = 9.0 Hz, 1H), 7.14 (ddd, J = 8.2, 7.0, 1.1 Hz, 1H), 7.05–6.98 (m, 2H), 6.90–6.81 (m, 2H), 5.10 (s, 1H), 4.09 (q, J = 7.1 Hz, 2H), 2.23 (m, 4H), 1.61 (p, J = 7.6 Hz, 2H), 1.45 (m, 1H), 1.25 (m, 1H), 1.21 (t, J = 7.1 Hz, 3H); 13C NMR (151 MHz, CDCl3 ) δ 203.5 (C=O), 173.8 (C=O), 160.9 (Cq), 137.7 (CH), 137.0 (Cq), 125.1 (CH), 125.0 (Cq), 122.8 (CH), 122.3 (CH), 120.7 (Cq), 120.0 (CH), 120.0 (CH), 119.0 (CH), 114.6 (Cq), 112.4 (CH), 111.8 (CH), 69.3(Cq), 60.4 (CH2), 37.0 (CH2), 34.2 (CH2), 25.2 (CH2), 23.1 (CH2), 14.3 (CH3); HR-ESIMS m/z calcd for C23H25N2O3 [M + H]+ 377.1860, found 377.1862.
2-(4-Methyl-1H-indol-3-yl)-2-phenylindolin-3-one (5l). According to procedure B, 5l was obtained as a yellow solid in 98% yield (33.2 mg; flash chromatographic condition: petroleum ether-acetone 85:15). 1H NMR (600 MHz, CDCl3) δ 8.44 (s, 1H), 7.72 (dd, J = 7.8, 1.3 Hz, 1H), 7.53 (ddd, J = 8.4, 7.1, 1.4 Hz, 1H), 7.41–7.35 (m, 2H), 7.31–7.23 (m, 5H), 7.15–7.10 (m, 1H), 7.00–6.91 (m, 2H), 6.86 (dt, J = 7.2, 1.0 Hz, 1H), 5.33 (s, 1H), 2.09 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 201.2 (C=O), 160.6 (Cq), 141.6 (Cq), 138.1 (Cq), 137.7 (CH), 129.7 (Cq), 128.7 (CH, 2C), 127.7 (CH), 126.6 (CH), 125.8 (CH, 2C), 125.1 (CH), 124.6 (Cq), 122.8 (CH), 122.5 (CH), 120.1 (CH), 119.8 (Cq), 114.3 (Cq), 113.5 (CH), 109.6 (CH), 72.4 (Cq), 21.9 (CH3); HR-ESIMS m/z calcd for C23H19N2O [M + H]+ 339.1492, found 339.1496.
2-(5-Chloro-1H-indol-3-yl)-2-phenylindolin-3-one (5m). According to procedure B, 5m was obtained as a yellow solid in 90% yield (32.3 mg; flash chromatographic condition: petroleum ether-acetone 85:15). 1H NMR (600 MHz, CDCl3) δ 8.54 (s, 1H), 7.67 (d, J = 7.8 Hz, 1H), 7.57–7.47 (m, 3H), 7.32–7.27 (m, 3H), 7.22 (d, J = 8.6 Hz, 1H), 7.12 (s, 2H), 7.09 (dd, J = 8.5, 2.0 Hz, 1H), 6.94 (d, J = 8.3 Hz, 1H), 6.89 (t, J = 7.4 Hz, 1H), 5.43 (s, 1H); 13C NMR (151 MHz, CDCl3) δ 200.8 (C=O), 160.6 (Cq), 139.3 (CH), 137.9 (Cq), 135.5 (Cq), 128.7 (CH, 2C), 128.1 (CH), 126.8 (CH, 2C), 125.7 (CH), 125.3 (Cq), 123.0(CH), 119.9 (CH), 119.5 (Cq), 119.3 (CH), 115.3 (Cq), 113.0 (CH), 112.9 (Cq), 71.3 (Cq); HR-ESIMS m/z calcd for C22H16ClN2O [M + H]+ 359.0946, found 359.0949.
2-(5-Methyl-1H-indol-3-yl)-2-phenylindolin-3-one (5n). According to procedure B, 5n was obtained as a yellow solid in 95% yield (32.2 mg; flash chromatographic condition: petroleum ether-acetone 85:15). 1H NMR (600 MHz, CDCl3) δ 8.21 (s, 1H), 7.70 (d, J = 7.8 Hz, 1H), 7.59–7.54 (m, 2H), 7.51 (ddd, J = 8.3, 7.1, 1.4 Hz, 1H), 7.34–7.28 (m, 3H), 7.25 (dd, J = 8.3, 2.9 Hz, 1H), 7.10 (d, J = 5.1 Hz, 1H), 7.01 (d, J = 8.3 Hz, 1H), 6.96 (s, 1H), 6.93 (d, J = 8.2 Hz, 1H), 6.90 (t, J = 7.4 Hz, 1H), 5.45 (s, 1H), 2.32 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 200.8 (C=O), 160.8 (Cq), 139.6 (Cq), 137.6 (CH), 135.4 (Cq), 129.4 (CH), 128.5 (CH, 2C), 127.8 (CH), 126.9 (CH, 2C), 125.9 (Cq), 125.7 (CH), 124.2 (CH), 124.0 (Cq), 119.7 (CH), 119.6 (Cq), 119.3 (CH), 114.7 (Cq), 113.0 (CH), 111.5 (CH), 71.5 (Cq), 21.6 (CH3),; HR-ESIMS m/z calcd for C23H19N2O [M + H]+ 339.1492, found 339.1494.
2-(5-Methoxy-1H-indol-3-yl)-2-phenylindolin-3-one (5o). According to procedure B, 5o was obtained as a yellow solid in 98% yield (34.8mg; flash chromatographic condition: petroleum ether-acetone 85:15). 1H NMR (600 MHz, CDCl3) 1H NMR (600 MHz, CDCl3) δ 8.14 (s, 1H), 7.70 (dd, J = 7.8, 1.3 Hz, 1H), 7.65–7.57 (m, 2H), 7.52 (ddd, J = 8.3, 7.1, 1.3 Hz, 1H), 7.36–7.23 (m, 4H), 7.08 (d, J = 5.8 Hz, 1H), 6.94 (d, J = 8.2 Hz, 1H), 6.90 (t, J = 7.4 Hz, 1H), 6.83 (dd, J = 8.6, 2.4 Hz, 1H), 6.57 (d, J = 2.4 Hz, 1H), 5.40 (s, 1H), 3.61 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 200.8 (C=O), 160.5 (Cq), 153.9 (CH), 139.3 (CH), 137.5 (Cq), 132.0 (Cq), 128.3 (CH, 2C), 127.7 (CH), 126.8 (CH, 2C), 126.0 (CH), 125.4 (CH), 124.6 (Cq), 119.6 (Cq), 119.6 (CH), 115.4 (Cq), 112.8 (CH), 112.3 (Cq), 112.2 (CH), 101.8 (CH), 71.2 (Cq), 55.5 (CH3); HR-ESIMS m/z calcd for C23H19N2O2 [M + H]+ 355.1441, found 355.1444.
2-(6-Methyl-1H-indol-3-yl)-2-phenylindolin-3-one (5p). According to procedure B, 5p was obtained as a yellow solid in 94% yield (31.9 mg; flash chromatographic condition: petroleum ether-acetone 85:15). 1H NMR (600 MHz, CDCl3) δ 8.11 (s, 1H), 7.70 (d, J = 7.8 Hz, 1H), 7.59–7.54 (m, 2H), 7.51 (ddd, J = 8.3, 7.1, 1.4 Hz, 1H), 7.33–7.27 (m, 3H), 7.16 (s, 1H), 7.08–7.02 (m, 2H), 6.94–6.87 (m, 2H), 6.83 (dd, J = 8.3, 1.3 Hz, 1H), 5.38 (s, 1H), 2.42 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 200.8 (C=O), 160.7 (Cq), 139.7 (Cq), 137.6 (CH), 137.5 (Cq), 132.5 (Cq), 128.5 (CH, 2C), 127.8 (CH), 126.9 (CH, 2C), 125.7 (CH), 123.5 (Cq), 123.2 (Cq), 121.9 (CH), 119.7 (CH), 119.7 (CH), 119.4 (CH), 115.4 (Cq), 113.0 (CH), 111.7 (CH), 71.5 (Cq), 21.7 (CH3); HRMS m/z calcd for C23H19N2O [M + H]+ 339.1492, found 339.1494.
2-(7-Methyl-1H-indol-3-yl)-2-phenylindolin-3-one (5q). According to procedure B, 5q was obtained as a yellow solid in 91% yield (30.8 mg; flash chromatographic condition: petroleum ether-acetone 85:15). 1H NMR (600 MHz, CDCl3) δ 8.28 (s, 1H), 7.71 (d, J = 7.7 Hz, 1H), 7.61–7.55 (m, 2H), 7.51 (ddd, J = 8.4, 7.1, 1.4 Hz, 1H), 7.32–7.27 (m, 3H), 7.13 (s, 1H), 7.01 (dd, J = 19.3, 7.5 Hz, 2H), 6.95–6.87 (m, 3H), 5.45 (s, 1H), 2.46 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 200.8 (C=O), 160.7 (Cq), 139.6 (CH), 137.6 (Cq), 136.6 (Cq), 128.5 (CH, 2C), 127.8 (CH), 126.9 (CH, 2C), 125.7 (CH), 125.3 (CH), 123.6 (Cq), 123.1 (CH), 121.1 (Cq), 120.3 (CH), 119.7 (CH), 119.6 (Cq), 117.4 (CH), 115.9 (Cq), 113.0 (CH), 71.5 (Cq), 16.7 (CH3); HR-ESIMS m/z calcd for C23H19N2O [M + H]+ 339.1492, found 339.1495.
2-(3-Methyl-1H-indol-2-yl)-2-phenylindolin-3-one (5r). According to procedure C, 5r was obtained as a yellow solid in 90% yield (30.4 mg; flash chromatographic condition: petroleum ether-acetone 85:15). 1H NMR (600 MHz, CDCl3) δ 8.84 (s, 1H), 7.69 (d, J = 7.7 Hz, 1H), 7.59–7.53 (m, 2H), 7.36–7.29 (m, 6H), 7.20 (ddd, J = 8.2, 7.0, 1.2 Hz, 1H), 7.13 (t, J = 7.4 Hz, 1H), 7.01 (d, J = 8.3 Hz, 1H), 6.93 (t, J = 7.4 Hz, 1H), 5.43 (s, 1H), 2.22 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 201.1 (C=O), 161.0 (Cq), 139.6 (Cq), 138.3 (CH), 134.6 (Cq), 131.0 (Cq), 129.6 (Cq), 129.0 (CH, 2C), 128.5 (CH), 126.5 (CH, 2C), 125.8 (CH), 122.4 (CH), 120.3 (CH), 119.6 (Cq), 119.5 (CH), 118.6 (CH), 112.9 (CH), 111.2 (CH), 109.7 (Cq), 71.6 (Cq), 9.6 (CH3); HR-ESIMS m/z calcd for C23H19N2O [M + H]+ 339.1492, found 339.1490.
N-(2-(5-Methoxy-2-(3-oxo-2-phenylindolin-2-yl)-1H-indol-3-yl)ethyl)acetamide (5s). According to procedure C, 5s was obtained as a yellow solid in 92% yield (40.3 mg; flash chromatographic condition: petroleum ether-acetone 60:40). 1H NMR (600 MHz, CDCl3) δ 9.35 (s, 1H), 8.07 (s, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.43 (ddd, J = 8.3, 7.0, 1.3 Hz, 1H), 7.26–7.14 (m, 6H), 7.07 (d, J = 8.3 Hz, 1H), 6.89 (d, J = 2.4 Hz, 1H), 6.80 (dd, J = 8.8, 2.4 Hz, 1H), 6.72 (ddd, J = 7.8, 7.0, 0.8 Hz, 1H), 6.13 (s, 1H), 3.78 (s, 3H), 3.47–3.31 (m, 1H), 3.19–3.13 (m, 1H), 2.84–2.79 (m, 1H), 2.75–2.70 (m, 1H), 1.90 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 201.4 (C=O), 171.7 (C=O), 162.3 (Cq), 154.2 (Cq), 140.0 (Cq), 138.6 (CH), 133.1 (Cq), 129.7 (Cq), 129.0 (Cq), 128.9(CH, 2C), 128.2 (CH), 126.0(CH, 2C), 125.6 (CH), 118.8 (CH), 117.3 (Cq), 112.4 (CH), 112.3 (CH), 112.2 (CH), 110.0 (Cq), 100.2 (CH), 71.1 (Cq), 56.1 (CH3), 41.2 (CH2), 24.6 (CH2), 23.3 (CH3); HR-ESIMS m/z calcd for C27H26N3O3 [M + H]+ 440.1969, found 440.1965.
Methyl (2-(2-(3-oxo-2-phenylindolin-2-yl)-1H-indol-3-yl)ethyl)carbamate (5t). According to procedure C, 5t was obtained as a yellow solid in 90% yield (38.2 mg; flash chromatographic condition: petroleum ether-acetone 60:40). 1H NMR (600 MHz, CDCl3) δ 9.46 (s, 1H), 7.74 (s, 1H), 7.61 (d, J = 7.8 Hz, 1H), 7.56–7.46 (m, 2H), 7.37 (d, J = 8.1 Hz, 1H), 7.30–7.16 (m, 6H), 7.15–7.08 (m, 2H), 6.80 (t, J = 7.4 Hz, 1H), 5.13 (s, 1H), 3.71 (s, 3H), 3.40–3.34 (m, 1H), 3.24–3.19 (m, 1H), 3.03–2.98 (m, 1H), 2.85–2.81 (m, 1H); 13C NMR (151 MHz, CDCl3) δ 201.5 (C=O), 162.2 (Cq), 158.2 (C=O), 140.1 (Cq), 138.6 (CH), 134.6 (Cq), 132.1 (Cq), 128.9 (CH, 2C), 128.6 (Cq), 128.3 (CH), 126.2 (CH, 2C), 125.7 (CH), 122.4 (CH), 119.7 (CH), 118.9 (CH), 118.1 (CH), 117.6 (Cq), 112.4 (CH), 111.6 (CH), 110.5 (Cq), 71.2 (Cq), 52.5 (CH3), 42.2 (CH2), 25.3 (CH2); HR-ESIMS m/z calcd for C26H24N3O3 [M + H]+ 426.1812, found 426.1815.
2-Phenyl-2-(2-phenyl-1H-indol-3-yl)indolin-3-one (6a). According to procedure D, 6a was obtained as a yellow solid in 98% yield (19.2 mg; flash chromatographic condition: petroleum ether-acetone 85:15). 1H NMR (600 MHz, acetone-d6) δ 10.38 (s, 1H), 7.58–7.53 (m, 2H), 7.51 (ddd, J = 8.3, 7.1, 1.3 Hz, 1H), 7.40 (d, J = 8.1 Hz, 1H), 7.28 (d, J = 7.6 Hz, 1H), 7.22–7.14 (m, 4H), 7.14–7.04 (m, 6H), 7.02 (d, J = 8.2 Hz, 1H), 6.81–6.74 (m, 3H); 13C NMR (151 MHz, acetone-d6) δ 200.9 (C=O), 160.9 (Cq), 141.7 (Cq), 138.8 (Cq), 138.0 (CH), 137.2 (Cq), 134.6 (Cq), 130.6 (CH, 2C), 128.8 (Cq), 128.6 (CH, 2C), 128.4 (CH), 128.5 (CH, 2C), 128.1 (CH, 2C), 127.9 (CH), 125.4 (CH), 122.3 (CH), 121.9 (CH), 120.8 (Cq), 119.8 (CH), 119.0 (Cq), 118.9 (CH), 113.1 (CH), 111.9 (CH), 72.5 (Cq); HR-ESIMS m/z calcd for C28H21N2O [M + H]+ 401.1648, found 401.1652.
2-Methyl-2-(2-methyl-1H-indol-3-yl)indolin-3-one (6b). According to procedure D, 6b was obtained as a yellow solid in 90% yield (12.5 mg; flash chromatographic condition: petroleum ether-acetone 85:15). 1H NMR (600 MHz, CDCl3) δ 7.86 (s, 1H), 7.72–7.69 (m, 1H), 7.51 (d, J = 0.9 Hz, 1H), 7.40 (d, J = 8.1 Hz, 1H), 7.24–7.22 (m, 1H), 7.08–7.04 (m, 1H), 6.96 (s, 1H), 6.93–6.85 (m, 3H), 2.42 (s, 3H), 1.92 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 204.4 (C=O), 159.7 (Cq), 137.6 (CH), 135.0 (Cq), 132.7 (Cq), 127.6 (Cq), 125.5 (CH), 121.4 (CH), 119.9 (CH), 119.7 (CH), 119.2 (CH), 112.6 (CH), 110.6 (CH), 110.3 (Cq), 109.7 (Cq), 67.3 (Cq), 25.2 (CH3), 14.8 (CH3); HR-ESIMS m/z calcd for C18H17N2O [M + H]+ 277.1335, found 277.1336.
4-Fluoro-2-(4-fluoro-2-phenyl-1H-indol-3-yl)-2-phenylindolin-3-one (6c). According to procedure D, 6c was obtained as a yellow solid in 88% yield (19.2 mg; flash chromatographic condition: petroleum ether-acetone 85:15). 1H NMR (600 MHz, DMSO-d6) δ 11.64 (s, 1H), 8.62 (s, 1H), 7.48 (d, J = 5.6 Hz, 1H), 7.28–7.23 (m, 2H), 7.20 (d, J = 8.1 Hz, 1H), 7.18–7.04 (m, 6H), 6.96 (d, J = 2.5 Hz, 3H), 6.83 (d, J = 8.3 Hz, 1H), 6.65–6.60 (m, 1H), 6.37 (dd, J = 9.5, 8.0 Hz, 1H); 13C NMR (151 MHz, DMSO-d6) δ 196.4, 160.9, 160.9, 160.0, 158.3, 155.9, 154.3, 139.4, 139.3, 138.7, 138.6, 138.5, 138.4, 132.7, 129.7, 127.6, 127.4, 127.1, 126.9, 122.2, 122.1, 115.8, 108.2, 107.7, 107.7, 107.6, 107.6, 104.6, 104.5, 102.9, 102.8, 79.2, 71.4; HR-ESIMS m/z calcd for C28H19F2N2O [M + H]+ 437.1460, found 437.1461.
5-Chloro-2-(5-chloro-2-phenyl-1H-indol-3-yl)-2-phenylindolin-3-one (6d). According to procedure D, 6d was obtained as a yellow solid in 91% yield (21.4 mg; flash chromatographic condition: petroleum ether-acetone 85:15). 1H NMR (600 MHz, CDCl3) δ 8.17 (s, 1H), 7.44–7.40 (m, 2H), 7.37 (dd, J = 8.6, 2.2 Hz, 1H), 7.32 (d, J = 2.2 Hz, 1H), 7.32–7.28 (m, 1H), 7.25–7.21 (m, 4H), 7.20–7.16 (m, 2H), 7.15–7.12 (m, 2H), 7.10 (dd, J = 8.6, 2.0 Hz, 1H), 6.90 (d, J = 2.0 Hz, 1H), 6.62 (d, J = 8.6 Hz, 1H), 5.12 (s, 1H); 13C NMR (151 MHz, CDCl3) δ 199.1 (C=O), 157.4 (Cq), 139.7 (Cq), 138.5 (Cq), 137.3 (CH), 133.9 (Cq), 132.9 (Cq), 129.8 (CH, 2C), 128.8 (CH), 128.7 (CH, 2C), 128.4 (Cq), 128.2 (CH), 128.0 (CH, 2C), 127.2 (CH, 2C), 125.8 (Cq), 124.7 (CH), 124.5 (Cq), 123.0 (CH), 121.3 (Cq), 121.1 (CH), 113.5 (CH), 111.9 (CH), 111.6 (Cq), 72.9 (Cq); HR-ESIMS m/z calcd for C28H19Cl2N2O [M + H]+ 469.0869, found 469.0869.
5-Methyl-2-(5-methyl-2-phenyl-1H-indol-3-yl)-2-phenylindolin-3-one (6e). According to procedure D, 6e was obtained as a yellow solid in 96% yield (20.6 mg; flash chromatographic condition: petroleum ether-acetone 85:15). 1H NMR (600 MHz, CDCl3) δ 7.99 (s, 1H), 7.54–7.42 (m, 2H), 7.28 (dd, J = 8.3, 1.9 Hz, 1H), 7.25–7.22 (m, 1H), 7.22–7.21 (m, 1H), 7.19 (d, J = 8.2 Hz, 1H), 7.18–7.14 (m, 3H), 7.15–7.11 (m, 4H), 6.97 (dd, J = 8.3, 1.6 Hz, 1H), 6.82–6.80 (m, 1H), 6.65 (d, J = 8.2 Hz, 1H), 5.02 (s, 1H), 2.29 (s, 3H), 2.25(s, 3H); 13C NMR (151 MHz, CDCl3) δ 200.7 (C=O), 158.0 (Cq), 140.8 (Cq), 138.6 (CH), 137.3 (Cq), 134.0 (Cq), 133.6 (Cq), 129.9 (CH, 2C), 129.2 (Cq), 128.9 (Cq), 128.3 (CH, 2C), 128.2 (CH), 127.8 (Cq), 127.7 (CH, 2C), 127.5 (CH), 127.4 (CH, 2C), 124.8 (CH), 124.1 (CH), 121.3 (CH), 120.9 (Cq), 112.5 (CH), 111.9 (Cq), 110.5 (CH), 72.7 (Cq), 21.8(CH3), 20.7(CH3); HR-ESIMS m/z calcd for C30H25N2O [M + H]+ 429.1961, found 429.1963.
5-Methoxy-2-(5-methoxy-2-phenyl-1H-indol-3-yl)-2-phenylindolin-3-one (6f). According to procedure D, 6f was obtained as a yellow solid in 98% yield (22.6 mg; flash chromatographic condition: petroleum ether-acetone 85:15). 1H NMR (600 MHz, CDCl3) δ 8.05 (s, 1H), 7.61–7.49 (m, 2H), 7.25–7.19 (m, 2H), 7.20–7.16 (m, 3H), 7.15–7.12 (m, 2H), 7.12–7.10 (m, 3H), 6.82 (d, J = 2.7 Hz, 1H), 6.78 (dd, J = 8.8, 2.4 Hz, 1H), 6.72 (dd, J = 8.8, 0.5 Hz, 1H), 6.36 (d, J = 2.4 Hz, 1H), 4.96 (s, 1H), 3.72 (s, 3H), 3.51 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 200.9 (C=O), 155.2 (Cq), 153.9 (Cq), 153.8 (Cq), 140.6 (Cq), 137.7 (Cq), 133.4 (Cq), 130.7 (Cq), 129.8 (CH. 2C), 128.3 (CH, 2C), 128.3 (CH), 128.0 (Cq), 127.7 (CH), 127.7(CH, 2C), 127.6 (CH), 127.5(CH, 2C), 121.2 (Cq), 114.2 (CH), 112.7 (CH), 112.3 (Cq), 111.5 (CH), 105.3 (CH), 103.3 (CH), 73.1 (Cq), 55.9(CH3), 55.5(CH3); HR-ESIMS m/z calcd for C30H25N2O3 [M + H]+ 461.1860, found 461.1860.
6-Methyl-2-(6-methyl-2-phenyl-1H-indol-3-yl)-2-phenylindolin-3-one (6g). According to procedure D, 6g was obtained as a yellow solid in 95% yield (20.3 mg; flash chromatographic condition: petroleum ether-acetone 85:15). 1H NMR (600 MHz, acetone-d6) δ 10.19 (s, 1H), 7.51 (d, J = 7.7 Hz, 2H), 7.20–7.16 (m, 4H), 7.14 (s, 1H), 7.09–7.04 (m, 6H), 6.82 (s, 1H), 6.67 (d, J = 8.3 Hz, 1H), 6.61 (d, J = 8.2 Hz, 2H), 2.37 (s, 3H), 2.35 (s, 3H); 13C NMR (151 MHz, acetone-d6) δ 200.1 (C=O), 161.3 (Cq), 149.2 (Cq), 142.0 (Cq), 138.1 (Cq), 137.6 (Cq), 134.8 (Cq), 131.7 (CH), 130.6 (CH, 2C), 128.4 (CH, 2C), 128.2 (CH, 2C), 128.1 (CH), 128.0 (CH, 2C), 127.7 (CH), 126.8 (Cq), 125.1 (CH), 121.7 (CH), 121.5 (CH), 120.6 (Cq), 120.6 (Cq), 118.7 (Cq), 112.9 (CH), 111.7 (CH), 72.7 (Cq), 22.5(CH3), 21.6(CH3); HR-ESIMS m/z calcd for C30H25N2O [M + H]+ 429.1961, found 429.1962.
7-Methyl-2-(7-methyl-2-phenyl-1H-indol-3-yl)-2-phenylindolin-3-one (6h). According to procedure D, 6h was obtained as a yellow solid in 92% yield (19.8 mg; flash chromatographic condition: petroleum ether-acetone 85:15). 1H NMR (600 MHz, CDCl3) δ 7.97 (s, 1H), 7.57–7.43 (m, 2H), 7.33–7.28 (m, 2H), 7.24 (dt, J = 7.1, 1.1 Hz, 1H), 7.23–7.19 (m, 3H), 7.19–7.15 (m, 3H), 6.99–6.91 (m, 2H), 6.87 (dd, J = 8.2, 7.1 Hz, 1H), 6.74 (t, J = 7.4 Hz, 1H), 4.89 (s, 1H), 2.45 (s, 3H), 1.94 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 200.9 (C=O), 158.5 (Cq), 141.0 (Cq), 137.1 (CH), 136.7 (Cq), 135.3 (Cq), 134.0 (Cq), 133.6 (Cq), 129.8 (CH, 2C), 129.2 (Cq), 128.4 (CH, 2C), 128.0 (CH, 2C), 127.7 (CH), 127.5 (CH, 2C), 127.0 (Cq), 123.1 (CH), 122.8 (CH), 121.4 (CH), 120.4 (CH), 119.9 (CH), 119.9 (Cq), 119.4 (CH), 112.6 (Cq), 72.4 (Cq), 16.7 (CH3), 15.6 (CH3); HR-ESIMS m/z calcd for C30H25N2O [M + H]+ 429.1961, found 429.1965.
[3,2′:2′,3″-Terindolin]-3′-one (7a). According to procedure D, 7a was obtained as a yellow solid in 75% yield (18.1 mg; flash chromatographic condition: petroleum ether-acetone 80:20). 1H NMR (600 MHz, acetone-d6) δ 10.16 (s, 2H), 7.56 (d, J = 7.7 Hz, 1H), 7.53–7.49 (m, 1H), 7.46 (d, J = 8.1 Hz, 2H), 7.38 (d, J = 8.2 Hz, 2H), 7.26–7.22 (m, 2H), 7.15 (s, 1H), 7.07–7.01 (m, 3H), 6.84 (ddd, J = 8.1, 7.0, 1.1 Hz, 2H), 6.82–6.77 (m, 1H); 13C NMR (151 MHz, acetone-d6) δ 201.4 (C=O), 161.6 (Cq), 138.4 (Cq, 2C), 138.0 (CH), 127.1 (CH), 125.4 (Cq, 2C), 125.0 (CH, 2C), 122.2 (CH, 2C), 121.8 (CH, 2C), 120.1 (Cq), 119.5 (CH, 2C), 118.6 (CH), 116.0 (CH), 113.1 (Cq, 2C), 112.3 (CH, 2C), 69.0 (Cq); HR-ESIMS m/z calcd for C24H18N3O [M + H]+ 364.1444, found 364.1445.
4,4′,4″-Trifluoro-[3,2′:2′,3″-terindolin]-3′-one (7b). According to procedure D, 7b was obtained as a yellow solid in 74% yield (20.5 mg; flash chromatographic condition: petroleum ether-acetone 80:20). 1H NMR (600 MHz, DMSO-d6) δ 11.29 (s, 2H), 7.69 (s, 1H), 7.43–7.37 (m, 1H), 7.24 (d, J = 8.1 Hz, 2H), 7.10–7.05 (m, 2H), 6.90 (s, 2H), 6.76 (d, J = 8.2 Hz, 1H), 6.71–6.66 (m, 2H), 6.40–6.36 (m, 1H); 13C NMR (151 MHz, DMSO-d6) δ 196.8, 161.6, 161.5, 160.0, 158.3, 156.2, 154.5, 140.0, 140.0, 138.4, 138.4, 125.6, 122.1, 122.0, 114.2, 114.1, 112.1, 112.1, 108.7, 108.7, 108.3, 108.3, 107.0, 106.9, 104.3, 104.2, 102.3, 102.2, 67.2; HR-ESIMS m/z calcd for C24H15F3N3O [M + H]+ 418.1162, found 418.1162.
5,5′,5″-Trifluoro-[3,2′:2′,3″-terindolin]-3′-one (7c). According to procedure D, 7c was obtained as a yellow solid in 73% yield (20.3 mg; flash chromatographic condition: petroleum ether-acetone 80:20).1H NMR (600 MHz, CDCl3) δ 8.08 (s, 2H), 7.38 (dd, J = 7.2, 2.7 Hz, 1H), 7.34–7.26 (m, 2H), 7.25 (s, 1H), 7.18 (s, 2H), 7.06–7.02 (m, 2H), 6.93–6.87 (m, 3H), 5.25 (s, 1H); 13C NMR (151 MHz, CDCl3) δ 200.7, 200.7, 158.5, 157.8, 156.9, 156.8, 156.2, 133.5, 126.0, 125.9, 125.8, 125.5, 120.5, 120.4, 114.9, 114.8, 114.4, 114.4, 112.3, 112.3, 111.1, 110.9, 110.3, 110.2, 105.4, 105.3, 69.0; HR-ESIMS m/z calcd for C24H15F3N3O [M + H]+ 418.1162, found 418.1163.
5,5′,5″-Trimethyl-[3,2′:2′,3″-terindolin]-3′-one (7d). According to procedure D, 7d was obtained as a yellow solid in 72% yield (19.4 mg; flash chromatographic condition: petroleum ether-acetone 80:20). 1H NMR (600 MHz, acetone-d6) δ 10.00 (s, 2H), 7.38–7.34 (m, 2H), 7.28–7.24 (m, 4H), 7.16 (d, J = 2.6 Hz, 2H), 6.96 (dd, J = 8.9, 1.7 Hz, 1H), 6.90–6.84 (m, 3H), 2.29 (s, 3H), 2.22 (s, 6H); 13C NMR (151 MHz, acetone-d6) δ 201.6 (C=O), 160.3 (Cq), 139.3 (CH), 136.9 (Cq, 2C), 128.1 (Cq, 2C), 127.5 (Cq, 2C), 125.1 (CH, 2C), 125.0 (Cq), 124.8 (CH), 123.9 (CH, 2C), 121.6 (CH, 2C), 120.6 (Cq), 115.8 (Cq, 2C), 113.3 (CH), 112.1 (CH, 2C), 69.6 (Cq), 21.9 (CH3, 2C), 20.7 (CH3); HR-ESIMS m/z calcd for C27H24N3O [M + H]+ 406.1914, found 406.1915.
5,5′,5″-Trimethoxy-[3,2′:2′,3″-terindolin]-3′-one (7e). According to procedure D, 7e was obtained as a yellow solid in 66% yield (19.9 mg; flash chromatographic condition: petroleum ether-acetone 80:20). 1H NMR (600 MHz, DMSO-d6) δ 10.79 (s, 2H), 7.79 (s, 1H), 7.27–7.22 (m, 3H), 7.05 (d, J = 2.5 Hz, 2H), 6.99 (s, 1H), 6.95 (d, J = 8.8 Hz, 1H), 6.82 (d, J = 2.5 Hz, 2H), 6.72–6.70 (m, 2H), 3.73 (s, 3H), 3.54 (s, 6H). 13C NMR (151 MHz, DMSO-d6) δ 201.2 (C=O), 156.9 (Cq), 152.6 (Cq, 2C), 151.8 (Cq), 132.1 (Cq, 2C), 127.8 (Cq), 126.1 (Cq, 2C), 124.7 (CH, 2C), 118.0 (CH), 113.7 (Cq, 2C), 113.5 (CH), 112.1 (CH, 2C), 110.6 (CH, 2C), 104.6 (CH), 103.1 (CH, 2C), 68.5 (Cq), 55.6 (CH3), 55.1 (CH3, 2C); HR-ESIMS m/z calcd for C27H24N3O4 [M + H]+ 454.1761, found 454.1761.
6,6′,6″-Trimethyl-[3,2′:2′,3″-terindolin]-3′-one (7f). According to procedure D, 7f was obtained as a yellow solid in 64% yield (17.3 mg; flash chromatographic condition: petroleum ether-acetone 80:20). 1H NMR (600 MHz, acetone-d6) δ 9.97 (s, 2H), 7.43 (d, J = 7.9 Hz, 1H), 7.32 (d, J = 8.1 Hz, 2H), 7.16 (s, 2H), 7.15–7.12 (m, 2H), 6.95 (s, 1H), 6.68 (dd, J = 8.2, 1.5 Hz, 2H), 6.63 (dt, J = 7.9, 1.5 Hz, 1H), 2.35 (s, 3H), 2.34 (s, 6H); 13C NMR (151 MHz, acetone-d6) δ 199.7 (C=O), 161.1 (Cq), 148.1 (Cq), 137.9 (Cq, 2C), 130.6 (Cq, 2C), 124.3 (CH, 2C), 124.2 (CH), 123.3 (Cq, 2C), 120.7 (CH, 2C), 120.3 (CH, 2C), 119.4 (CH), 117.2 (Cq), 115.3 (CH, 2C), 112.1 (CH), 111.2 (Cq, 2C), 68.4 (Cq), 21.6 (CH3), 20.8 (CH3, 2C); HR-ESIMS m/z calcd for C27H24N3O [M + H]+406.1914, found 406.1916.
7,7′,7″-Trimethyl-[3,2′:2′,3″-terindolin]-3′-one (7g). According to procedure D, 7g was obtained as a yellow solid in 65% yield (17.6 mg; flash chromatographic condition: petroleum ether-acetone 80:20). 1H NMR (600 MHz, acetone-d6) δ 8.01 (s, 2H), 7.63–7.58 (m, 1H), 7.35 (dt, J = 7.1, 1.2 Hz, 1H), 7.27 (s, 1H), 7.08 (d, J = 2.3 Hz, 2H), 6.97 (dt, J = 7.1, 1.1 Hz, 2H), 6.91 (dd, J = 8.0, 7.1 Hz, 2H), 6.85 (t, J = 7.5 Hz, 1H), 5.28 (s, 1H), 2.45 (s, 6H), 2.22 (s, 3H); 13C NMR (151 MHz, acetone-d6) δ 201.7 (C=O), 159.7 (Cq), 137.6 (CH), 136.7 (CH), 125.4 (Cq, 2C), 124.1 (Cq, 2C), 122.9 (CH), 122.8 (CH, 2C), 122.1 (Cq), 120.8 (Cq, 2C), 120.2 (CH, 2C), 119.8 (Cq), 119.6 (CH, 2C), 118.2 (CH, 2C), 115.8 (Cq, 2C), 68.6 (Cq), 16.7 (CH3, 2C), 15.9 (CH3); HR-ESIMS m/z calcd for C27H24N3O [M + H]+ 406.1914, found 406.1911.
2-Phenyl-2-(1H-pyrrol-2-yl)indolin-3-one (8). According to procedure B, 8 was obtained as a yellow solid in 94% yield (25.9 mg; flash chromatographic condition: petroleum ether-acetone 80:20). 1H NMR (600 MHz, CDCl3) δ 8.84 (s, 1H), 7.65 (d, J = 7.8 Hz, 1H), 7.51 (ddd, J = 8.4, 7.1, 1.4 Hz, 1H), 7.32–7.21 (m, 5H), 6.94 (d, J = 8.3 Hz, 1H), 6.91–6.86 (m, 1H), 6.79 (td, J = 2.7, 1.5 Hz, 1H), 6.27 (ddd, J = 3.9, 2.6, 1.5 Hz, 1H), 6.21 (dt, J = 3.5, 2.7 Hz, 1H), 5.38 (s, 1H); 13C NMR (151 MHz, CDCl3) δ 201.2 (C=O), 161.0 (Cq), 140.8 (Cq), 138.0 (CH), 129.1 (Cq), 128.9 (CH, 2C), 128.4 (CH), 126.8 (CH, 2C), 125.7 (CH), 119.9 (CH), 119.6 (Cq), 118.7 (CH), 112.8 (CH), 108.5 (CH), 107.2 (CH), 71.0 (Cq); HR-ESIMS m/z calcd for C18H15N2O [M + H]+ 275.1179, found 275.1177.
2-(1-Methyl-1H-pyrrol-3-yl)-2-phenylindolin-3-one(9). According to procedure B, 9 was obtained as a yellow solid in 90% yield (25.9 mg; flash chromatographic condition: petroleum ether-acetone 85:15). 1H NMR (600 MHz, CDCl3) δ 7.62 (d, J = 7.6 Hz, 1H), 7.52 (dd, J = 5.3, 3.4 Hz, 2H), 7.45 (ddd, J = 8.3, 7.1, 1.3 Hz, 1H), 7.31–7.26 (m, 2H), 7.24 (ddd, J = 7.2, 4.3, 1.3 Hz, 1H), 6.90 (d, J = 8.2 Hz, 1H), 6.84–6.80 (m, 1H), 6.56 (dt, J = 5.0, 2.2 Hz, 2H), 5.98 (dd, J = 2.6, 1.9 Hz, 1H), 5.15 (s, 1H), 3.56 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 201.3 (C=O), 160.4 (Cq), 140.9 (Cq), 137.4 (CH), 128.3 (CH, 2C), 127.6 (CH), 126.9 (CH, 2C), 125.6 (CH), 123.9 (Cq), 122.6 (CH), 120.8 (CH), 119.7 (Cq), 119.4 (CH), 112.7 (CH), 107.3 (CH), 71.3 (CH), 36.3 (CH3); HR-ESIMS m/z calcd for C19H17N2O [M + H]+ 289.1335, found 289.1333.
2-Phenyl-2-(thiophen-2-yl)indolin-3-one (10). According to procedure B, 10 was obtained as a yellow solid in 75% yield (21.8 mg; flash chromatographic condition: petroleum ether-acetone 80:20). 1H NMR (600 MHz, CDCl3) δ 7.67 (d, J = 7.7 Hz, 1H), 7.56–7.45 (m, 3H), 7.39–7.29 (m, 3H), 7.25 (d, J = 5.2 Hz, 1H), 7.12 (dd, J = 3.7, 1.2 Hz, 1H), 7.00 (dd, J = 5.1, 3.6 Hz, 1H), 6.96 (d, J = 8.2 Hz, 1H), 6.91 (t, J = 7.4 Hz, 1H), 5.35 (s, 1H); 13C NMR (151 MHz, CDCl3) δ 199.4 (C=O), 160.0 (Cq), 144.6 (Cq), 140.5 (Cq), 137.9 (CH), 128.7 (CH, 2C), 128.4 (CH), 127.3 (CH), 126.9 (CH, 2C), 126.4 (CH), 125.9 (CH), 125.4 (CH), 120.2 (CH), 119.4 (Cq), 112.8 (CH), 72.4 (Cq); HR-ESIMS m/z calcd for C18H14NOS [M + H]+ 292.0791, found 292.0791.
2-(3-Oxo-2-phenylindolin-2-yl)acetaldehyde (11). According to procedure B, 11 was obtained as a yellow solid in 72% yield (18.1 mg; flash chromatographic condition: petroleum ether-acetone 90:10). 1H NMR (600 MHz, CDCl3) δ 9.70 (d, J = 1.7 Hz, 1H), 7.59 (d, J = 7.7 Hz, 1H), 7.53–7.49 (m, 3H), 7.36–7.32 (m, 2H), 7.30–7.28 (m, 1H), 6.97 (d, J = 8.3 Hz, 1H), 6.86 (t, J = 7.4 Hz, 1H), 5.70 (s, 1H), 3.64 (dd, J = 17.6, 1.9 Hz, 1H), 2.98 (d, J = 17.5 Hz, 1H); 13C NMR (151 MHz, CDCl3) δ 199.9 (C=O), 199.8 (C=O), 160.2 (Cq) 138.0 (CH), 137.7 (Cq), 129.1 (CH, 2C), 128.1 (CH), 125.8 (CH), 125.4 (CH, 2C), 119.6 (CH), 118.5 (Cq), 112.1 (CH), 68.7 (Cq), 50.4 (CH2); HR-ESIMS m/z calcd for C16H14NO2 [M + H]+ 252.1019, found 252.1021.
2-(2-Oxopropyl)-2-phenylindolin-3-one (12). According to procedure B using 5 equiv of MsOH as additive, 12 was obtained as a yellow solid in 70% yield (18.5 mg; flash chromatographic condition: petroleum ether-acetone 90:10). 1H NMR (600 MHz, CDCl3) δ 7.57–7.52 (m, 3H), 7.48 (ddd, J = 8.3, 7.0, 1.3 Hz, 1H), 7.34–7.30 (m, 2H), 7.28–7.22 (m, 1H), 6.95 (d, J = 8.3 Hz, 1H), 6.80 (t, J = 7.4 Hz, 1H), 6.13 (s, 1H), 3.73 (d, J = 17.4 Hz, 1H), 2.73 (d, J = 17.4 Hz, 1H), 2.10 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 206.9 (C=O), 200.4 (C=O), 160.2 (Cq), 137.9 (CH), 137.8 (Cq), 128.8 (CH, 2C), 127.8 (CH), 125.6 (CH), 125.5 (CH, 2C), 119.1 (CH), 118.3 (Cq), 112.0 (CH), 69.1 (Cq), 49.6 (CH2), 31.6 (CH3); HR-ESIMS m/z calcd for C17H16NO2 [M + H]+ 265.1103, found 2665.1101.

4. Conclusions

In summary, an oxidative cross-dehydrogenative coupling of indoles with 1,3-dicarbonyl compounds and indoles has been developed. The reaction proceeds smoothly under mild conditions and features a broad substrate scope with excellent functional group tolerance, affording structurally diverse 2,2-disubstituted indolin-3-ones in high yields. Oxidative dimerization or trimerization of indoles was achieved under the same conditions. Moreover, a variety of C-H nucleophiles such as pyrrole, thiophene, acetaldehyde, and acetone were also suitable substrates and all the 2,2-disubstituted indolin-3-ones were obtained as racemic molecules.

Supplementary Materials

The Supplementary Materials are available online.

Author Contributions

The work was designed by X.L. and H.Z.; Synthesis of compounds was performed by X.Y., Y.-D.T., and C.-S.J.; X.L. and X.Y. prepared the manuscript and H.Z. revised and edited it. All authors have read and agreed to the published version of the manuscript.

Funding

We gratefully acknowledge the National Natural Science Foundation of China (No. 21801093), the Natural Science Foundation of Shandong Province (Nos. ZR2017BB006, JQ201721), the Young Taishan Scholars Program (No. tsqn20161037), Shandong Talents Team Cultivation Plan of University Preponderant Discipline (No. 10027).

Conflicts of Interest

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

References

  1. Arndtsen, B.A.; Bergman, R.G.; Mobley, T.A.; Peterson, T.H. Selective Intermolecular Carbon-Hydrogen Bond Activation by Synthetic Metal Complexes in Homogeneous Solution. Acc. Chem. Res. 1995, 28, 154–162. [Google Scholar] [CrossRef]
  2. Wencel-Delord, J.; Dröge, T.; Liu, F.; Glorius, F. Towards mild metal-catalyzed C-H bond activation. Chem. Soc. Rev. 2011, 40, 4740–4761. [Google Scholar] [CrossRef] [PubMed]
  3. Roizen, J.L.; Harvey, M.E.; Du Bois, J. Metal-catalyzed nitrogen-atom transfer methods for the oxidation of aliphatic C-H bonds. Acc. Chem. Res. 2012, 45, 911–922. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  4. Colby, D.A.; Tsai, A.S.; Bergman, R.G.; Ellman, J.A. Rhodium catalyzed chelation-assisted C–H bond functionalization reactions. Acc. Chem. Res. 2012, 45, 814–825. [Google Scholar] [CrossRef] [PubMed]
  5. He, J.; Wasa, M.; Chan, K.S.L.; Shao, Q.; Yu, J.-Q. Palladium-catalyzed transformations of alkyl C-H bonds. Chem. Rev. 2016, 117, 8754–8786. [Google Scholar] [CrossRef] [PubMed]
  6. Wang, C.-S.; Dixneuf, P.H.; Soulé, J.-F. Photoredox catalysis for building C–C bonds from C(sp2)–H bonds. Chem. Rev. 2018, 118, 7532–7585. [Google Scholar] [CrossRef]
  7. Wang, H.; Gao, X.; Lv, Z.; Abdelilah, T.; Lei, A. Recent Advances in Oxidative R1-H/R2-H Cross-Coupling with Hydrogen Evolution via Photo-/Electrochemistry: Focus Review. Chem. Rev. 2019, 119, 6769–6787. [Google Scholar] [CrossRef]
  8. Scheuermann, C. Beyond traditional cross couplings: The scope of the cross dehydrogenative coupling reaction. Chem. Asian J. 2010, 5, 436–451. [Google Scholar] [CrossRef]
  9. Liu, C.; Yuan, J.; Gao, M.; Tang, S.; Li, W.; Shi, R.; Lei, A. Oxidative coupling between two hydrocarbons: An update of recent C–H functionalizations. Chem. Rev. 2015, 115, 12138–12204. [Google Scholar] [CrossRef]
  10. Yang, Y.; Lan, J.; You, J. Oxidative C–H/C–H coupling reactions between two (hetero) arenes. Chem. Rev. 2017, 117, 8787–8863. [Google Scholar] [CrossRef]
  11. Phillips, A.M.S.; Pombeiro, A.J.L. Recent Developments in Transition Metal-Catalyzed Cross-Dehydrogenative Coupling Reactions of Ethers and Thioethers. ChemCatChem 2018, 10, 3354–3383. [Google Scholar] [CrossRef]
  12. Ma, P.; Chen, H. Ligand-Dependent Multi-State Reactivity in Cobalt(III)-Catalyzed C-H Activations. ACS Catal. 2019, 9, 1962–1972. [Google Scholar] [CrossRef]
  13. Li, C. Cross-dehydrogenative coupling (CDC): Exploring C-C bond formations beyond functional group transformations. Acc. Chem. Res. 2009, 42, 335–344. [Google Scholar] [CrossRef] [PubMed]
  14. Yoo, W.-J.; Li, C.-J. Cross-Dehydrogenative Coupling Reactions of sp3-Hybridized C-H Bonds. In Topics in Current Chemistry; Springer: Berlin, Germany, 2009; Volume 292, pp. 281–302. [Google Scholar]
  15. Girard, S.A.; Knauber, T.; Li, C. The Cross-Dehydrogenative Coupling of C-H Bonds: A Versatile Strategy for C-C Bond Formations. Angew. Chem. Int. Ed. 2014, 53, 74–100. [Google Scholar] [CrossRef]
  16. Yeung, C.S.; Dong, V.M. Catalytic dehydrogenative cross-coupling: Forming carbon-carbon bonds by oxidizing two carbon-hydrogen bonds. Chem. Rev. 2011, 111, 1215–1292. [Google Scholar] [CrossRef]
  17. Ashenhurst, J.A. Intermolecular oxidative cross-coupling of arenes. Chem. Soc. Rev. 2010, 39, 540–548. [Google Scholar] [CrossRef]
  18. Liu, C.; Zhang, H.; Shi, W.; Lei, A. Bond formations between two nucleophiles: Transition metal catalyzed oxidative cross-coupling reactions. Chem. Rev. 2011, 111, 1780–1824. [Google Scholar] [CrossRef]
  19. Li, Z.; Li, C. CuBr-catalyzed direct indolation of tetrahydroisoquinolines via Cross-dehydrogenative coupling between sp3 C-H and sp2 C-H Bonds. J. Am. Chem. Soc. 2005, 127, 6968–6969. [Google Scholar] [CrossRef]
  20. Alagiri, K.; Kumara, G.S.R.; Prabhu, K.R. An oxidative cross-dehydrogenative-coupling reaction in water using molecular oxygen as the oxidant: Vanadium catalyzed indolation of tetrahydroisoquinolines. Chem. Commun. 2011, 47, 11787–11789. [Google Scholar] [CrossRef]
  21. Boess, E.; Schmitz, C.; Klussmann, M. A comparative mechanistic study of Cu-catalyzed oxidative coupling reactions with N-phenyltetrahydroisoquinoline. J. Am. Chem. Soc. 2012, 134, 5317–5325. [Google Scholar] [CrossRef]
  22. Ratnikov, M.O.; Xu, X.; Doyle, M.P. Simple and sustainable iron-catalyzed aerobic C-H functionalization of N,N-dialkylanilines. J. Am. Chem. Soc. 2013, 135, 9475–9479. [Google Scholar] [CrossRef] [PubMed]
  23. Li, K.; Tan, G.; Huang, J.; Song, F.; You, J. Iron-catalyzed oxidative C-H/C-H cross-coupling: An efficient route to α-quaternary α-amino acid derivatives. Angew. Chem. Int. Ed. 2013, 52, 12492–12495. [Google Scholar] [CrossRef] [PubMed]
  24. Zhong, J.; Wu, C.; Meng, Q.; Gao, X.; Lei, T.; Tung, C.; Wu, L. A Cascade Cross-Coupling and in Situ Hydrogenation Reaction by Visible Light Catalysis. Adv. Synth. Catal. 2014, 356, 2846–2852. [Google Scholar] [CrossRef]
  25. Xie, Z.; Liu, L.; Chen, W.; Zheng, H.; Xu, Q.; Yuan, H.; Lou, H. Practical Metal-Free C (sp3)-H Functionalization: Construction of Structurally Diverse α-Substituted N-Benzyl and N-Allyl Carbamates. Angew. Chem. Int. Ed. 2014, 53, 3904–3908. [Google Scholar] [CrossRef] [PubMed]
  26. Jin, L.; Feng, J.; Lu, G.; Cai, C. Di-tert-butyl Peroxide (DTBP)-Mediated Oxidative Cross-Coupling of Isochroman and Indole Derivatives. Adv. Synth. Catal. 2015, 357, 2105–2110. [Google Scholar] [CrossRef]
  27. Dutta, B.; Sharma, V.; Sassu, N.; Dang, Y.; Weerakkody, C.; Macharia, J.; Miao, R.; Howell, A.R.; Suib, S.L. Cross dehydrogenative coupling of N-aryltetrahydroisoquinolines (sp3 C-H) with indoles (sp2 C-H) using a heterogeneous mesoporous manganese oxide catalyst. Green Chem. 2017, 19, 5350–5355. [Google Scholar] [CrossRef]
  28. Patil, M.R.; Dedhia, N.P.; Kapdi, A.R.; Kumar, A.V. Cobalt (II)/N-Hydroxyphthalimide-catalyzed cross-dehydrogenative coupling reaction at room temperature under aerobic condition. J. Org. Chem. 2018, 83, 4477–4490. [Google Scholar] [CrossRef] [PubMed]
  29. Haldar, S.; Jana, C.K. Direct (het) arylation of tetrahydroisoquinolines via a metal and oxidant free C (sp 3)–H functionalization enabled three component reaction. Org. Biomol. Chem. 2019, 17, 1800–1804. [Google Scholar] [CrossRef]
  30. Ziegler, F.E.; Belema, M. Cyclization of Chiral Carbon-Centered Aziridinyl Radicals: A New Route to Azirino [2′,3′:3,4] pyrrolo [1,2-a] indoles. J. Org. Chem. 1994, 59, 7962–7967. [Google Scholar] [CrossRef]
  31. Benkovics, T.; Guzei, I.A.; Yoon, T.P. Oxaziridine-Mediated Oxyamination of Indoles: An Approach to 3-Aminoindoles and Enantiomerically Enriched 3-Aminopyrroloindolines. Angew. Chem. Int. Ed. 2010, 49, 9153–9157. [Google Scholar] [CrossRef]
  32. Li, J.; Liu, M.; Li, Q.; Tian, H.; Shi, Y. A facile approach to spirocyclic 2-azido indolines via azidation of indoles with ceric ammonium nitrate. Org. Biomol. Chem. 2014, 12, 9769–9772. [Google Scholar] [CrossRef] [PubMed]
  33. Tomakinian, T.; Guillot, R.; Kouklovsky, C.; Vincent, G. Direct Oxidative Coupling of N-Acetyl Indoles and Phenols for the Synthesis of Benzofuroindolines Related to Phalarine. Angew. Chem. Int. Ed. 2014, 53, 11881–11885. [Google Scholar] [CrossRef] [PubMed]
  34. Liu, K.; Tang, S.; Huang, P.; Lei, A. External oxidant-free electrooxidative [3+2] annulation between phenol and indole derivatives. Nat. Commun. 2017, 8, 775. [Google Scholar] [CrossRef] [PubMed]
  35. Ryzhakov, D.; Jarret, M.; Guillot, R.; Kouklovsky, C.; Vincent, G. Radical-mediated dearomatization of indoles with sulfinate reagents for the synthesis of fluorinated spirocyclic indolines. Org. Lett. 2017, 19, 6336–6339. [Google Scholar] [CrossRef]
  36. Kawada, M.; Sugihara, H.; Mikami, I.; Kawai, K.; Kuzuna, S.; Noguchi, S.; Sanno, Y. Spirocyclopropane Compounds. II. Synthesis and Biological Activities of Spiro [cyclopropane-1,2′-[2H] indol]-3′(1′H)-ones. Chem. Pharm. Bull. 1981, 29, 1912–1919. [Google Scholar] [CrossRef] [Green Version]
  37. Williams, R.M.; Glinka, T.; Kwast, E.; Coffman, H.; Stille, J.K. Asymmetric, stereocontrolled total synthesis of (−)-brevianamide B. J. Am. Chem. Soc. 1990, 112, 808–821. [Google Scholar] [CrossRef]
  38. Wu, P.L.; Hsu, Y.L.; Jao, C.W. Indole alkaloids from Cephalanceropsis gracilis. J. Nat. Prod. 2006, 69, 1467–1470. [Google Scholar] [CrossRef]
  39. Kato, H.; Yoshida, T.; Tokue, T.; Nojiri, Y.; Hirota, H.; Ohta, T.; Williams, R.M.; Tsukamoto, S. Notoamides A–D: Prenylated Indole Alkaloids Isolated from a Marine-Derived Fungus, Aspergillus sp. Angew. Chem. Int. Ed. 2007, 46, 2254–2256. [Google Scholar] [CrossRef]
  40. Tsukamoto, S.; Umaoka, H.; Yoshikawa, K.; Ikeda, T.; Hirota, H. Notoamide O, a Structurally Unprecedented Prenylated Indole Alkaloid, and Notoamides P−R from a Marine-Derived Fungus, Aspergillus sp. J. Nat. Prod. 2010, 73, 1438–1440. [Google Scholar] [CrossRef]
  41. Zhang, X.; Mu, T.; Zhan, F.; Ma, L.; Liang, G. Total Synthesis of (−)-Isatisine A. Angew. Chem. Int. Ed. 2011, 50, 6164–6166. [Google Scholar] [CrossRef]
  42. Abe, T.; Kukita, A.; Akiyama, K.; Naito, T.; Uemura, D. Isolation and structure of a novel biindole pigment substituted with an ethyl group from a metagenomic library derived from the marine sponge Halichondria okadai. Chem. Lett. 2012, 41, 728–729. [Google Scholar] [CrossRef]
  43. Kim, J.; Movassaghi, M. Biogenetically inspired syntheses of alkaloid natural products. Chem. Soc. Rev. 2009, 38, 3035–3050. [Google Scholar] [CrossRef]
  44. Liu, Y.H.; McWhorter, W.W. Synthesis of 8-Desbromohinckdentine A1. J. Am. Chem. Soc. 2003, 125, 4240–4252. [Google Scholar] [CrossRef] [PubMed]
  45. Steven, A.; Overman, L.E. Total synthesis of complex cyclotryptamine alkaloids: Stereocontrolled construction of quaternary carbon stereocenters. Angew. Chem. Int. Ed. 2007, 46, 5488–5508. [Google Scholar] [CrossRef] [PubMed]
  46. Han, S.; Movassaghi, M. Concise total synthesis and stereochemical revision of all (−)-Trigonoliimines. J. Am. Chem. Soc. 2011, 133, 10768–10771. [Google Scholar] [CrossRef] [Green Version]
  47. Arai, S.; Nakajima, M.; Nishida, A. A Concise and Versatile Synthesis of Alkaloids from Kopsia tenuis: Total Synthesis of (±)-Lundurine A and B. Angew. Chem. Int. Ed. 2014, 53, 5569–5572. [Google Scholar] [CrossRef]
  48. Wang, C.; Wang, Z.; Xie, X.; Yao, X.; Li, G.; Zu, L. Total Synthesis of (±)-Grandilodine B. Org. Lett. 2017, 19, 1828–1830. [Google Scholar] [CrossRef]
  49. Hutchison, A.J.; Kishi, Y. Stereospecific total synthesis of dl-austamide. J. Am. Chem. Soc. 1979, 101, 6786–6788. [Google Scholar] [CrossRef]
  50. Zhang, X.; Foote, C.S. Dimethyldioxirane oxidation of indole derivatives. Formation of novel indole-2,3-epoxides and a versatile synthetic route to indolinones and indolines. J. Am. Chem. Soc. 1993, 115, 8867–8868. [Google Scholar] [CrossRef]
  51. Higuchi, K.; Sato, Y.; Tsuchimochi, M.; Sugiura, K.; Hatori, M.; Kawasaki, T. First total synthesis of hinckdentine A. Org. Lett. 2009, 11, 197–199. [Google Scholar] [CrossRef]
  52. Ding, W.; Zhou, Q.Q.; Xuan, J.; Li, T.R.; Lu, L.Q.; Xiao, W.J. Photocatalytic aerobic oxidation/semipinacol rearrangement sequence: A concise route to the core of pseudoindoxyl alkaloids. Tetrahedron. Lett. 2014, 55, 4648–4652. [Google Scholar] [CrossRef]
  53. Schendera, E.; Lerch, S.; Von Drathen, T.; Unkel, L.N.; Brasholz, M. Phosphoric Acid Catalyzed 1, 2-Rearrangements of 3-Hydroxyindolenines to Indoxyls and 2-Oxindoles: Reagent-Controlled Regioselectivity Enabled by Dual Activation. Eur. J. Org. Chem. 2017, 22, 3134–3138. [Google Scholar] [CrossRef]
  54. Ardakani, M.A.; Smalley, R.K. Base-induced intramolecular cyclisation of o-azidophenyl sec-alkyl ketones. A new synthesis of 2,2-dialkylindoxyls. Tetrahedron Lett. 1979, 20, 4769–4772. [Google Scholar] [CrossRef]
  55. Azadi-Ardakani, M.; Alkhader, M.A.; Lippiatt, J.H.; Patel, D.I.; Smalley, R.K.; Higson, S. 2,2-Disubstituted-1,2-dihydro-3H-indol-3-ones by base-and thermal-induced cyclisations of o-azidophenyl s-alkyl ketones and o-azidobenzoyl esters. Chem. Soc. Perkin Trans. 1986, 1, 1107–1111. [Google Scholar] [CrossRef]
  56. Wetzel, A.; Gagosz, F. Gold-Catalyzed Transformation of 2-Alkynyl Arylazides: Efficient Access to the Valuable Pseudoindoxyl and Indolyl Frameworks. Angew. Chem. Int. Ed. 2011, 50, 7354–7358. [Google Scholar] [CrossRef]
  57. Goriya, Y.; Ramana, C.V. Synthesis of pseudo-indoxyl derivatives via sequential Cu-catalyzed SN Ar and Smalley cyclization. Chem. Commun. 2013, 49, 6376–6378. [Google Scholar] [CrossRef]
  58. Mothe, S.R.; Novianti, M.L.; Ayers, B.J.; Chan, P.W.H. Silver-Catalyzed Tandem Hydroamination/Hydroarylation of 1-(2-Allylamino) phenyl-4-hydroxy-but-2-yn-1-ones to 1′-Allylspiro [indene-1,2′-indolin]-3′-ones. Org. Lett. 2014, 16, 4110–4113. [Google Scholar] [CrossRef]
  59. Li, N.; Wang, T.Y.; Gong, L.Z.; Zhang, L. Gold-Catalyzed Multiple Cascade Reaction of 2-Alkynylphenylazides with Propargyl Alcohols. Chem. Eur. J. 2015, 21, 3585–3588. [Google Scholar] [CrossRef]
  60. Liu, R.R.; Ye, S.C.; Lu, C.J.; Zhuang, G.L.; Gao, J.R.; Jia, Y.X. Dual Catalysis for the Redox Annulation of Nitroalkynes with Indoles: Enantioselective Construction of Indolin-3-ones Bearing Quaternary Stereocenters. Angew. Chem. Int. Ed. 2015, 54, 11205–11208. [Google Scholar] [CrossRef]
  61. Li, Y.J.; Yan, N.; Liu, C.H.; Yu, Y.; Zhao, Y.L. Gold/Copper-Co-catalyzed Tandem Reactions of 2-Alkynylanilines: A Synthetic Strategy for the C2-Quaternary Indolin-3-ones. Org. Lett. 2017, 19, 1160–1163. [Google Scholar] [CrossRef]
  62. Fu, W.Q.; Song, Q.L. Copper-Catalyzed Radical Difluoroalkylation and Redox Annulation of Nitroalkynes for the Construction of C2-Tetrasubstituted Indolin-3-ones. Org. Lett. 2018, 20, 393–396. [Google Scholar] [CrossRef] [PubMed]
  63. Mérour, J.Y.; Chichereau, L.; Finet, J.P. Arylation of 3-oxo-2,3-dihydroindoles with aryllead triacetates. Tetrahedron Lett. 1992, 33, 3867–3870. [Google Scholar] [CrossRef]
  64. Rueping, M.; Raja, S.; Núñez, A. Asymmetric Brønsted acid-catalyzed Friedel–crafts reactions of indoles with cyclic imines-efficient generation of nitrogen-substituted quaternary carbon centers. Adv. Synth. Catal. 2011, 353, 563–568. [Google Scholar] [CrossRef]
  65. Jin, C.-Y.; Wang, Y.; Liu, Y.-Z.; Shen, C.; Xu, P.-F. Organocatalytic asymmetric Michael addition of oxindoles to nitroolefins for the synthesis of 2,2-disubstituted oxindoles bearing adjacent quaternary and tertiary stereocenters. J. Org. Chem. 2012, 77, 11307–11312. [Google Scholar] [CrossRef] [PubMed]
  66. Parra, A.; Alfaro, R.; Marzo, L.; Moreno-Carrasco, A.; Luis, J.; Ruano, G.; Alemán, J. Enantioselective aza-Henry reactions of cyclic α-carbonyl ketimines under bifunctional catalysis. Chem. Commun. 2012, 48, 9759–9761. [Google Scholar] [CrossRef]
  67. Liu, J.-X.; Zhou, Q.-Q.; Deng, J.-G.; Chen, Y.-C. An asymmetric normal-electron-demand aza-Diels-Alder reaction via trienamine catalysis. Org. Biomol. Chem. 2013, 11, 8175–8178. [Google Scholar] [CrossRef]
  68. Guo, C.; Schedler, M.; Daniliuc, C.G.; Glorius, F. N-Heterocyclic Carbene Catalyzed Formal [3+2] Annulation Reaction of Enals: An Efficient Enantioselective Access to Spiro-Heterocycles. Angew. Chem. Int. Ed. 2014, 53, 10232–10236. [Google Scholar] [CrossRef]
  69. Zhao, Y.-L.; Wang, Y.; Cao, J.; Liang, Y.-M.; Xu, P.-F. Organocatalytic Asymmetric Michael-Michael Cascade for the Construction of Highly Functionalized N-Fused Piperidinoindoline Derivatives. Org. Lett. 2014, 16, 2438–2441. [Google Scholar] [CrossRef]
  70. Huang, J.-R.; Qin, L.; Zhu, Y.-Q.; Song, Q.; Dong, L. Multi-site cyclization via initial C-H activation using a rhodium (iii) catalyst: Rapid assembly of frameworks containing indoles and indolines. Chem. Commun. 2015, 51, 2844–2847. [Google Scholar] [CrossRef]
  71. Dhara, K.; Mandal, T.; Das, J.; Dash, J. Synthesis of Carbazole Alkaloids by Ring-Closing Metathesis and Ring Rearrangement–Aromatization. Angew. Chem. Int. Ed. 2015, 54, 15831–15835. [Google Scholar] [CrossRef]
  72. Peng, J.-B.; Qi, Y.; Ma, A.-J.; Tu, Y.-Q.; Zhang, F.-M.; Wang, S.-H.; Zhang, S.-Y. Cascade oxidative dearomatization/semipinacol rearrangement: An approach to 2-spirocyclo-3-oxindole derivatives. Chem. Asian J. 2013, 8, 883–887. [Google Scholar] [CrossRef] [PubMed]
  73. Huang, H.; Cai, J.; Ji, X.; Xiao, F.; Chen, Y.; Deng, G.-J. Internal Oxidant-Triggered Aerobic Oxygenation and Cyclization of Indoles under Copper Catalysis. Angew. Chem. Int. Ed. 2016, 55, 307–311. [Google Scholar] [CrossRef] [PubMed]
  74. Kong, L.; Wang, M.; Zhang, F.; Xu, M.; Li, Y. Copper-Catalyzed Oxidative Dearomatization/Spirocyclization of Indole-2-Carboxamides: Synthesis of 2-Spiro-pseudoindoxyls. Org. Lett. 2016, 18, 6124–6127. [Google Scholar] [CrossRef] [PubMed]
  75. Yamashita, M.; Nishizono, Y.; Himekawa, S.; Iida, A. One-pot synthesis of polyhydropyrido [1,2-a] indoles and tetracyclic quinazolinones from 2-arylindoles using copper-mediated oxidative tandem reactions. Tetrahedron 2016, 72, 4123–4131. [Google Scholar] [CrossRef]
  76. Lu, F.Y.; Chen, Y.J.; Chen, Y.; Ding, X.; Guan, Z.; He, Y.H. Highly enantioselective electrosynthesis of C2-quaternary indolin-3-ones. Chem. Commun. 2020, 56, 623–626. [Google Scholar] [CrossRef] [PubMed]
  77. Altinis Kiraz, C.I.; Emge, T.J.; Jimenez, L.S. Oxidation of Indole Substrates by Oxodiperoxomolybdenum∙Trialkyl (aryl)-phosphine Oxide Complexes. J. Org. Chem. 2004, 69, 2200–2202. [Google Scholar] [CrossRef] [PubMed]
  78. Lin, F.; Chen, Y.; Wang, B.-S.; Qin, W.-B.; Liu, L.-X. Silver-catalyzed TEMPO oxidative homocoupling of indoles for the synthesis of 3,3′-biindolin-2-ones. RSC Adv. 2015, 5, 37018–37022. [Google Scholar] [CrossRef]
  79. Zhang, C.-H.; Li, S.-L.; Bureš, F.; Lee, R.; Ye, X.-Y.; Jiang, Z.-Y. Visible Light Photocatalytic Aerobic Oxygenation of Indoles and pH as a Chemoselective Switch. ACS Catal. 2016, 6, 6853–6860. [Google Scholar] [CrossRef]
  80. Deng, Z.-F.; Peng, X.-J.; Huang, P.-P.; Jiang, L.-L.; Ye, D.-N.; Liu, L.-X. A multifunctionalized strategy of indoles to C2-quaternary indolin-3-ones via a TEMPO/Pd-catalyzed cascade process. Org. Biomol. Chem. 2017, 15, 442–448. [Google Scholar] [CrossRef]
  81. Guchhait, S.K.; Chaudhary, V.; Rana, V.A.; Priyadarshani, G.; Kandekar, S.; Kashyap, M. Oxidative dearomatization of indoles via Pd-catalyzed C–H oxygenation: An entry to C2-quaternary indolin-3-ones. Org. Lett. 2016, 18, 1534–1537. [Google Scholar] [CrossRef]
  82. Ding, X.; Dong, C.; Guan, Z.; He, Y. Concurrent Asymmetric Reactions Combining Photocatalysis and Enzyme Catalysis: Direct Enantioselective Synthesis of 2,2-Disubstituted Indol-3-ones from 2-Arylindoles. Angew. Chem. Int. Ed. 2019, 58, 118–124. [Google Scholar] [CrossRef]
  83. Jiang, X.; Zhu, B.; Lin, K.; Wang, G.; Su, W.; Yu, C. Metal-free synthesis of 2,2-disubstituted indolin-3-ones. Org. Biomol. Chem. 2019, 17, 2199–2203. [Google Scholar] [CrossRef] [PubMed]
  84. Liu, X.; Yan, X.; Tang, Y.; Jiang, C.-S.; Yu, J.-H.; Wang, K.; Zhang, H. Direct oxidative dearomatization of indoles: Access to structurally diverse 2,2-disubstituted indolin-3-ones. Chem. Commun. 2019, 55, 6535–6538. [Google Scholar] [CrossRef] [PubMed]
  85. Liu, X.; Yan, X.; Yu, J.-H.; Tang, Y.; Wang, K.; Zhang, H. Organocatalytic Asymmetric Dearomative Oxyalkylation of Indoles Enables Access to C2-Quaternary Indolin-3-ones. Org. Lett. 2019, 21, 5626–5629. [Google Scholar] [CrossRef] [PubMed]
  86. Cacchi, S.; Fabrizi, G. Synthesis and functionalization of indoles through palladium-catalyzed reactions. Chem. Rev. 2005, 105, 2873–2920. [Google Scholar] [CrossRef]
  87. Bartoli, G.; Bencivenni, G.; Dalpozzo, R. Organocatalytic strategies for the asymmetric functionalization of indoles. Chem. Soc. Rev. 2010, 39, 4449–4465. [Google Scholar] [CrossRef]
  88. Liu, J.-F.; Jiang, Z.-Y.; Wang, R.-R.; Zheng, Y.-T.; Chen, J.-J.; Zhang, X.-M.; Ma, Y.-B. Isatisine A, a novel alkaloid with an unprecedented skeleton from leaves of Isatis indigotica. Org. Lett. 2007, 9, 4127–4129. [Google Scholar] [CrossRef]
  89. Meng, Z.; Sun, S.; Yuan, H.; Lou, H.; Liu, L. Catalytic Enantioselective Oxidative Cross-Coupling of Benzylic Ethers with Aldehydes. Angew. Chem. Int. Ed. 2014, 53, 543–547. [Google Scholar] [CrossRef]
  90. Liu, X.; Meng, Z.; Li, C.; Lou, H.; Liu, L. Organocatalytic Enantioselective Oxidative C-H Alkenylation and Arylation of N-Carbamoyl Tetrahydropyridines and Tetrahydro-β-carbolines. Angew. Chem. Int. Ed. 2015, 54, 6012–6015. [Google Scholar] [CrossRef]
  91. Sun, S.; Li, C.; Floreancig, P.E.; Lou, H.; Liu, L. Highly enantioselective catalytic cross-dehydrogenative coupling of N-carbamoyl tetrahydroisoquinolines and terminal alkynes. Org. lett. 2015, 17, 1684–1687. [Google Scholar] [CrossRef]
  92. Liu, X.; Sun, S.; Meng, Z.; Lou, H.; Liu, L. Organocatalytic asymmetric C–H vinylation and arylation of N-acyl tetrahydroisoquinolines. Org. lett. 2015, 17, 2396–2399. [Google Scholar] [CrossRef] [PubMed]
  93. Wan, M.; Sun, S.; Li, Y.; Liu, L. Organocatalytic Redox Deracemization of Cyclic Benzylic Ethers Enabled by An Acetal Pool Strategy. Angew. Chem. Int. Ed. 2017, 56, 5116–5202. [Google Scholar] [CrossRef] [PubMed]
Sample Availability: All samples of the compounds are available from the authors.
Molecules 25 00419 g001 550
Figure 1. Representative bioactive natural products with 2,2-disubstituted indolin-3-one motif.
Figure 1. Representative bioactive natural products with 2,2-disubstituted indolin-3-one motif.
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Molecules 25 00419 g002 550
Figure 2. Oxidative dearomative cross-dehydrogenative coupling of indoles with various C-H nucleophiles.
Figure 2. Oxidative dearomative cross-dehydrogenative coupling of indoles with various C-H nucleophiles.
Molecules 25 00419 g002
Molecules 25 00419 g003 550
Figure 3. Cross-dehydrogenative coupling of indoles with 1,3-dicarbonyl compounds.
Figure 3. Cross-dehydrogenative coupling of indoles with 1,3-dicarbonyl compounds.
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Molecules 25 00419 g004 550
Figure 4. Cross-dehydrogenative coupling of indoles with dissimilar indole substrates.
Figure 4. Cross-dehydrogenative coupling of indoles with dissimilar indole substrates.
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Molecules 25 00419 g005 550
Figure 5. Oxidative dimerization and trimerization of indoles.
Figure 5. Oxidative dimerization and trimerization of indoles.
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Molecules 25 00419 g006 550
Figure 6. Cross-dehydrogenative coupling of indoles with various C-H nucleophiles.
Figure 6. Cross-dehydrogenative coupling of indoles with various C-H nucleophiles.
Molecules 25 00419 g006
Table
Table 1. Optimization of reaction conditions [a].
Table 1. Optimization of reaction conditions [a].
Molecules 25 00419 i001
EntryOxidantadditiveYield (%) [b]
3a6a
1TEMPO+ClO4−-096
2TEMPO+ClO4−CuCl797
3TEMPO+ClO4−CuCl286<5
4TEMPO+ClO4−Cu(OTf)295-
5TEMPO+ClO4−Zn(OTf)292-
6TEMPO+ClO4−Yb(OTf)240<5
7TEMPO+OTf−Cu(OTf)293-
8TEMPO+BF4−Cu(OTf)298-
9TEMPO+PF6−Cu(OTf)290-
10 [c]TEMPO+BF4−Cu(OTf)298-
11 [d]TEMPO+BF4−--98
[a] Reaction conditions: 1a (0.1 mmol), 2a (0.2 mmol), additive (0.05 eq.) and oxidant (0.1 mmol) in THF (1.0 mL) at room temperature. [b] Yield of isolated product. [c] 0.005 eq. Cu(OTf)2 was added. [d] The reaction was performed without extra nucleophile.

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Yan, X.; Tang, Y.-D.; Jiang, C.-S.; Liu, X.; Zhang, H. Oxidative Dearomative Cross-Dehydrogenative Coupling of Indoles with Diverse C-H Nucleophiles: Efficient Approach to 2,2-Disubstituted Indolin-3-ones. Molecules 2020, 25, 419. https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25020419

AMA Style

Yan X, Tang Y-D, Jiang C-S, Liu X, Zhang H. Oxidative Dearomative Cross-Dehydrogenative Coupling of Indoles with Diverse C-H Nucleophiles: Efficient Approach to 2,2-Disubstituted Indolin-3-ones. Molecules. 2020; 25(2):419. https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25020419

Chicago/Turabian Style

Yan, Xue, Ying-De Tang, Cheng-Shi Jiang, Xigong Liu, and Hua Zhang. 2020. "Oxidative Dearomative Cross-Dehydrogenative Coupling of Indoles with Diverse C-H Nucleophiles: Efficient Approach to 2,2-Disubstituted Indolin-3-ones" Molecules 25, no. 2: 419. https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25020419

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