Rearrangement of 5-Indolyl-3-pyrrolin-2-ones into Privileged 4-Indolyl-3-pyrrolin-2-ones Leads to Identification of Antiproliferative Compounds Active under Hypoxia

Dmitrii A Aksenov; Connor Edvall; Shivendran Vytheswaran; Puppala Sathish; Alesia S Akulova; Nicolai A Aksenov; Tatyana S Galushko; Tayyaba Hasan; Alexander V Aksenov; Sanku Mallik; Mohammad A Saad; Alexander Kornienko

doi:10.1021/acs.joc.5c02314

. Author manuscript; available in PMC: 2026 Feb 26.

Published in final edited form as: J Org Chem. 2026 Jan 16;91(4):1571–1587. doi: 10.1021/acs.joc.5c02314

Rearrangement of 5-Indolyl-3-pyrrolin-2-ones into Privileged 4-Indolyl-3-pyrrolin-2-ones Leads to Identification of Antiproliferative Compounds Active under Hypoxia

Dmitrii A Aksenov ^1,^#, Connor Edvall ^2,^#, Shivendran Vytheswaran ^3,^#, Puppala Sathish ⁴, Alesia S Akulova ⁵, Nicolai A Aksenov ⁶, Tatyana S Galushko ⁷, Tayyaba Hasan ⁸, Alexander V Aksenov ⁹, Sanku Mallik ¹⁰, Mohammad A Saad ¹¹, Alexander Kornienko ¹²

¹Department of Chemistry, North Caucasus Federal University, Stavropol 355009, Russian Federation

²Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota 58105, United States

³Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, United States

⁴Department of Chemistry and Biochemistry, Texas State University, San Marcos, Texas 78666, United States

⁵Department of Chemistry, North Caucasus Federal University, Stavropol 355009, Russian Federation

⁶Department of Chemistry, North Caucasus Federal University, Stavropol 355009, Russian Federation

⁷Department of Chemistry, North Caucasus Federal University, Stavropol 355009, Russian Federation

⁸Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, United States; Division of Health Sciences and Technology, Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts 02115, United States

⁹Department of Chemistry, North Caucasus Federal University, Stavropol 355009, Russian Federation

¹⁰Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota 58105, United States

¹¹Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, United States

¹²Department of Chemistry and Biochemistry, Texas State University, San Marcos, Texas 78666, United States

Author Contributions

D.A.A., C.E., and S.V. contributed equally

^✉

Corresponding Authors: Alexander V. Aksenov – Department of Chemistry, North Caucasus Federal University, Stavropol 355009, Russian Federation; aaksenov@ncfu.ru, Sanku Mallik – Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota 58105, United States; sanku.mallik@ndsu.edu, Mohammad A. Saad – Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, United States; msaad1@mgh.harvard.edu, Alexander Kornienko – Department of Chemistry and Biochemistry, Texas State University, San Marcos, Texas 78666, United States; a_k76@txstate.edu

PMCID: PMC12933247 NIHMSID: NIHMS2141551 PMID: 41544024

Abstract

Herein, we describe a synthetic route toward privileged 4-indolyl-3,5-diaryl-3-pyrrolin-2-ones based on a previously reported Friedel–Crafts reaction of 5-hydroxy-3,5-diaryl-3-pyrrolin-2-ones with indole. The intermediate 5-indolyl-3,5-diaryl-3-pyrrolin-2-ones are not isolated but further reacted under one-pot conditions, leading to the indole moiety migration from position C5 to position C4 of the 3-pyrrolin-2-one ring. The optimal reaction conditions found involved stirring with 2 equiv of aluminum chloride in 1,4-dioxane to complete the Friedel–Crafts step and then heating at 130 °C for 40 min in a microwave reactor to achieve the rearrangement step. Using the developed chemistry, a variety of compounds were prepared for biological testing, including those oxidized at C5 because 5-hydroxy-3-pyrrolin-2-ones have been reported to possess diverse biological properties as well. The synthesized compounds were tested for antiproliferative activities against MDA-MB-231 triple-negative breast cancer cells under normoxic and hypoxic conditions at a single concentration of 10 μM, and a number of compounds belonging to each of the series were identified to have noteworthy antiproliferative action under both normoxia and hypoxia. Several compounds from each series were further tested against ovarian cancer cells, and compounds from each series were capable of reducing cell viability of chemotherapy-resistant OVCAR-5 cells by as much as 75–80% at a concentration of 5 μM.

Graphical Abstract

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INTRODUCTION

Since the introduction of the concept by Evans and co-workers in 1988,¹ the utilization of “privileged structures” in modern drug discovery has become an established strategy to generate collections of compounds with high likelihood of biological activities.² Indolylmaleimides and 4-indolyl-3-pyrrolin-2-ones are one type of a privileged scaffold (Figure 1), where the five-membered nitrogen-containing heterocycle (blue) places the indole aromatic system (red) within a vicinal cis-position with another aryl ring (black).

Figure 1. — Structures of biologically active indolylmaleimides and 4-indolyl-3-pyrrolin-2-ones.

Selected examples of bioactive compounds based on this scaffold include a highly potent VEGF-R2/3 inhibitor 1 with an IC₅₀ of 31/37 nM and were found to strongly block angiogenesis in an in vivo model.³ Indolylmaleimide SB-216763 is a classical glycogen synthase kinase 3 inhibitor with over 500 publications describing its use for this purpose. Some recent results, for example, describe its ability to maintain mouse embryonic stem cells (mESCs) in a pluripotent state for more than two months, a finding of potential importance in regenerative medicine.⁴ Primary amine-containing indolylmaleimides of the general structure 2 were found to be potent, with the IC₅₀ values down to 34 nM, inhibitors of Ca²⁺/calmodulin-dependent protein kinases, with these molecules binding at the ATP-active site and the protonated amine making a hydrogen bond contact with Glu106.⁵ Finally, a system containing three aromatic rings, such as 3, was designed using a five-membered core with a three-finger pharmacophore model to inhibit the Mdm2–p53 interaction.⁶ Compound 3 was synthesized and found to be an Mdm2 antagonist with an IC₅₀ of <1 μM.⁶

Synthetically, these molecules are accessed predominantly through organometallic coupling reactions that deliver the aromatic residues (red and black in Figure 1) onto the maleimide or γ-lactam (blue in Figure 1) template. An example of the synthesis of Mdm2 antagonist 3 is shown in Figure 2, as it illustrates the challenges one faces when putting together this privileged scaffold, especially in the case of an unsymmetrical γ-lactam system.⁶

Figure 2. — Illustrative synthesis of 4-indolyl-3-pyrrolin-2-one 3.

Transformation of dibromide 5, accessible from N-methylpyrrole, to indolylmaleimide 6 involves the addition of N–H deprotonated 6-chloroindole with subsequent bromide elimination. The indole N-protection as Boc then gives 6 (Figure 2). Installation of the chlorobenzyl moiety in 7 was then achieved using the Suzuki–Miyaura reaction. The problem step was introduction of the next chlorobenzyl group using the Grignard reaction as the desired compound 9 was obtained as a minor addition product, and the entire design of the synthesis did not include a strategy for differentiation between the two carbonyls of the maleimide template. Removal of the protecting group from 9 then afforded indolyl-γ-lactam 3 with substantial material loss in the final stages of the synthetic pathway. Thus, the inspection of this instructive example and additional synthetic literature in this area^3,7,8 reveals that novel processes involving strategies allowing to differentiate the carbonyls of the 5-membered core maleimide as well as transition-metal—and protecting group—free methodologies would be highly beneficial. In this contribution, we describe a synthetic transformation serendipitously discovered that we believe fulfills some of these criteria and thus could find applications in the construction of medicinally relevant compounds based on the abovementioned privileged scaffolds. Furthermore, our evaluations of these compounds against cancer cells reveal their antiproliferative activity, as would not be unexpected due to the privileged status of the prepared compounds.

RESULTS AND DISCUSSION

We have previously reported Friedel–Crafts alkylation at indole C-3 (10) by 5-hydroxy-3-pyrrolin-2-one 11 to give 5-indolyl-3-pyrrolin-2-one 12 (Figure 3a).⁹ In our explorations of the types of chemistry associated with compounds 12, we attempted a gramine-like process involving ring opening A→B (Figure 3b) and trapping the ring-opened species with cyanide with the expectation to obtain 13aa when 12aa was treated with KCN and TsOH in hot n-BuOH. To our surprise, we isolated 4-indolyl-3-pyrrolin-2-one 14aa, in which the indole moiety rearranged from position C5 of the γ-lactam ring to C4.

Realizing the importance of this “privileged scaffold” in drug discovery as discussed in the Introduction section (Figure 1), we made an effort to optimize this initial modest 26% yield and found right away that the yield was virtually unchanged if 10a was reacted with 11a and Friedel–Crafts product 12aa was not isolated but reacted further under one-pot conditions to yield the desired rearranged compound 14aa (Table 1, entry 1). Optimization of this one-pot process initially centered on the use of various strong protic acids, but the highest yield we were able to achieve was 44% (entry 6). However, the application of a Lewis acid, such as AlCl₃, and microwave heating in 1,4-dioxane gave the highest 66% yield (entry 9).

Table 1.

Optimization of Conditions for the Synthesis of 4-Indolyl-3,5-diaryl-3-pyrrolin-2-ones


#	reagent	solvent	conditions	yield (%)
1	TsOH	1-butanol	rt for 0.5 h, then reflux, 2 h	25
2	TsOH	2-butanol	rt for 0.5 h, then reflux, 1.5 h	37
3	TsOH	1,2-dichloroethane	rt for 1 h, then reflux, 2 h	42
4	TsOH	MeCN	rt for 0.75 h, then reflux, 3 h	22
5	H₃PO₃	HCOOH	rt for 0.5 h, then reflux, 1 h	0^a
6	MsOH	AcOH	rt for 0.5 h, then reflux, 1 h	44
7	AcOH	EtOH	rt for 0.5 h, then reflux, 1 h	0^b
8	ZnCl₂	2-butanol	reflux, 2 h	0^c
9	AlCl₃	1,4-dioxane	rt for 0.5 h, then 130 °C, MW, 40 min	66
10	AlCl₃	2-butanol	rt for 0.5 h, then reflux, 1 h	51
11	AlCl₃	2-butanol	rt for 0.5 h, then 130 °C, MW, 40 min	57

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The rearrangement did not take place, and the Friedel-Crafts product 12aa was isolated in 64% yield.

Similar to the previous one, 12aa was isolated in 58% yield.

Similar to the previous one, 12aa was isolated in 70% yield.

Next, we studied the reaction scope. We found that under optimized conditions, the process worked for the preparation of 4-indolyl-3,5-diaryl-3-pyrrolin-2-ones containing alkyl groups (14ab–af), alkoxy groups (14ag–ak), and halogens (14al–an). Another interesting finding is that the migratory ability can be extended to both electron-donor (14ba) and electron-acceptor (14ea, 14fa, and 14ga) substituted indoles as well as naphthols (14ca) and phenols (14da). The overall yields of compounds 14 are moderate and range from 30 to 66%, but given the complexity of the transformation, the values of the obtained materials are acceptable from a practical perspective. The structures of the final products are clearly established from their NMR spectra, most notably the appearance of H5-proton at δ 5.7–6.0 in ¹H NMR, and confirmed via X-ray analysis of, for example, compound 14ac (Figure 4 and 5). The crystals of this compound suitable for Xray structural work were obtained from the benzene–petroleum ether mixed solvent system, where the material was first dissolved in hot benzene and then upon cooling petroleum ether was added to induce slow crystallization.

Figure 4. — Investigation of the rearrangement scope by preparing diversely substituted 4-indolyl-3,5-diaryl-3-pyrrolin-2-ones and related compounds.

Figure 5. — X-ray structure of **14ac** (a) depicted in panel (b); thermal ellipsoids are shown at 50% probability (CCDC2472264).

The proposed mechanism for indole C5→C4 rearrangement is shown in Figure 6. The protic or Lewis acid activates the 5-hydroxy-3-pyrrolin-2-one 11 component toward the Friedel–Crafts reaction by transforming it into highly electrophilic acyliminum ion A→B. The electrophilic alkylation of indole occurs at position C3 to form 5-indolyl-3-pyrrolin-2-ones C. Subsequent acid activation of D promotes intramolecular Michael addition to give spiro-cyclopropane E. Relevant transformations at C3 of indole involving intramolecular Michael attack leading to spiro-adducts have been described,^10,11 including reactions leading to spiro-cyclopropanes.^12,13 Ring opening of the strained spiro-cyclopropane in E with the formation of acyliminium in F is followed by tautomerization events F→G→H. While we invoke the aromatic form G as a plausible tautomer on route F→H, we do not observe it either by NMR in solution or by X-ray in crystal form. The 4-indolyl-3,5-diaryl-3-pyrrolin-2-one representation of these compounds as shown by structure H is the observed tautomeric form for these compounds.

To compare the biological properties of 5-indolyl-3-pyrrolin-2-ones 12 with the rearranged 4-indolyl-3-pyrrolin-2-ones 14, we isolated these Friedel–Crafts addition products by performing the first step only (Figure 7). Here, we used the new Lewis acid-based conditions developed in this work compared with protic acid catalysis utilized by us previously, which allowed us to obtain significantly higher yields of 5-indolyl-3-pyrrolin-2-ones 12a–n (Figure 7). Since all these compounds are also intermediates toward the rearranged products 14, the same substitution pattern on aromatic rings of 5-hydroxy-3-pyrrolin-2-ones 11a–n worked equally well here as well and the reaction also worked with nonindole electron-rich aromatic compounds to give naphthol (12ca) and phenol (12da), although their yields were somewhat lower.

Figure 7. — Preparation of diversely substituted 5-indolyl-3,5-diaryl-3-pyrrolin-2-ones and related compounds using the newly developed conditions.

Due to the biological activity of the 5-hydroxylated variant of these structures as represented by molecule 3 (Figure 1) as well as related literature on 5-hydroxy-3-pyrrolin-2-ones with different reported biological properties, such as platelet aggregation inhibitory,¹⁴ neuritogenic,¹⁵ anticomplementary,¹⁶ anti-MRSA,¹⁷ we furthered our compound collection diversity for this structural type by oxidizing selected rearranged molecules 14. To achieve transformation of 14aa→15aa, we screened various oxidizing reagents and reaction conditions as summarized in Table 2.

Table 2.

Optimization of Reaction Conditions for the Oxidation of 4-Indolyl-3,5-diaryl-3-pyrrolin-2-ones


#	reagent	solvent	temperature	yield (%)
1	TsOH	DMSO	120 °C	58
2		DMSO	160 °C	42
3	H₂O₂	PhH	rt	23
4	H₂O₂	CH₂Cl₂	rt	12
5	SiO₂	MeCN	reflux	53
6	SeO₂	HCOOH	reflux	82

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For example, a DMSO-based oxidation (entries 1 and 2, Table 2)¹⁸ was moderately successful in this context, whereas peroxide-promoted oxidations (entries 3 and 4)¹⁹ did not give us the expected results. Interestingly, a molecular oxygen-promoted oxidation on the surface of silica gel (entry 5)²⁰ was also moderately successful here, and this method should be definitely further investigated for controlled oxidations of benzylic and allylic positions due to its “green nature.” For the purpose of this investigation, however, we found that selenium dioxide^21,22 in refluxing acetonitrile (entry 6) gave us the highest yield of 15aa, and we chose these conditions for the preparation of C5-oxidized 5-hydroxyl-4-indolyl-3-pyrrolin-2-ones 15 (Figure 8).

Figure 8. — Oxidation at C5 within the 3-pyrrolin-2-one scaffold.

We began our initial evaluation of the synthesized compound for biological activities. Thus, we grouped them into three privileged classes, i.e., 4-indolyl-3-pyrrolin-2-ones 14 (from Figure 4), 5-indolyl-3-pyrrolin-2-ones 12 (from Figure 7), and 5-hydroxy-4-indolyl-3-pyrrolin-2-ones 15 (from Figure 8) and tested them at 10 μM single concentration against MDA-MB-231 triple-negative breast cancer cells (Figure 9). It should be noted that this cell line is commonly used to model late-stage metastatic breast cancer.²³ The experiments were performed under normoxic (21% oxygen) and hypoxic (0.2% oxygen) conditions to mimic the microenvironment of solid triple-negative breast tumors. Hypoxia, a clinically relevant feature of solid tumors, strongly reduces the efficacy of conventional cancer treatments, such as chemotherapy and radiation therapy. The reduction of oxygen in proliferating and advanced tumors leads to a series of genetic, transcriptional, and metabolic changes that promote survival, metastasis, and a clinically malignant phenotype.²⁴ For example, it was reported that hypoxia significantly increased resistance of MDA-MB-231 triple-negative breast cancer cells to cisplatin, a drug used to treat triple-negative breast cancer, by raising its inhibitory IC₅₀ from 17 μM under normoxia to 330 μM under hypoxia.²⁵ Hypoxia also induced resistance of MDA-MB-231 cells to etoposide, daunorubicin, doxorubicin, and mitoxantrone.²⁶ Thus, it was important to ascertain whether our active compounds retained activity under hypoxic conditions. It was interesting to discover that moderate levels of activity were found among each of these groups, although the structure–activity preferences were different in each series. Thus, the most potent compounds incorporated different types of aromatic substituents in each series, e.g., among compounds 14, unsubstituted 3,5-diphenyl compound 14aa led to cell viability decrease by ca. 50% (Figure 9a); among compounds 12, it was compound 12ba containing unsubstituted 3,5-diphenyl rings but incorporating C2-methyl in the indole that led to cell viability decrease by ca. 50% (Figure 9b); finally, among 5-hydroxyl compounds 15, the best one was compound 15ae with the p-isopropyl group in 3-phenyl ring, which led to cell viability decrease by ca. 75% at 10 μM (Figure 9c). And importantly, the compound activities did not seem to be affected by hypoxic conditions.

Figure 9. — Percent cell viability upon treatment with (a) 4-indolyl-3-pyrrolin-2-ones 14, (b) 5-indolyl-3-pyrrolin-2-ones 12, and (c) 5-hydroxy-4-indolyl-3-pyrrolin-2-ones 15. The MDA-MB-231 triple-negative breast cancer was treated at a 10 μM concentration for 72 h. The cell viability of DMSO control is 100%, determined with the Alamar Blue assay.

As the compounds demonstrated the ability to overcome cancer cell resistance to chemotherapy, we further evaluated a few selected analogues from each series against ovarian cancer cells, A2780 and OVCAR-5, which were chosen due to differences in their drug sensitivity. While A2780 cells represent a drug-sensitive cell line and have been shown to be responsive to several chemotherapeutic agents including platinum-based therapeutics, OVCAR-5 is a treatment-resistant model with low response to platinum-based therapies.^27–29 Here, similar to the breast cancer testing results (Figure 9), compounds 14ac and 15af were found to be least potent across both cell lines (Table 3), necessitating the concentration to be raised to 25–50 μM in order to achieve 70–80% cell viability decrease. On the other hand, compounds 14aa, 12af, 12af, and 15ae, representing all three of the synthesized structural subtypes, demonstrated high cytotoxicities against both cell lines even at the lowest tested concentration of 5 μM (Table 3). Interestingly, the performance of these compounds was comparable for both the cell lines, with a decrease in relative viability of approximately 75%, highlighting their therapeutic potential for both treatment-sensitive and treatment-resistant ovarian cancers.³⁰

Table 3.

Percent Ovarian Cancer Cell Viability upon Treatment with Two Selected Compounds from Each of the Structural Subtypes^a

	A2780						OVCAR-5
	5 μM		10 μM		25 μM		5 μM		10 μM		25 μM		50 μM
compound	viab. %	SD %	viab. %	SD %	viab. %	SD %	viab. %	SD %	viab. %	SD %	viab. %	SD %	viab. %	SD %
14aa	20.6	9.2	20.2	8.2	20.9	8.8	41.6	22.6	21.6	3.9	21.6	4.5	18.0	1.5
14ac	79.0	11.8	63.1	9.8	32.3	13.3	100.3	10.2	109.1	14.5	61.7	28.3	18.7	1.9
12ad	20.4	8.7	20.6	8.4	21.7	9.2	23.8	5.4	21.5	4.0	22.2	4.3	21.7	2.1
12af	20.3	8.8	20.5	8.4	26.2	21.3	24.6	4.2	22.1	4.4	21.6	4.3	19.8	1.5
15ae	19.2	8.3	19.5	8.4	20.2	8.1	22.9	4.2	20.9	4.6	20.6	4.4	18.1	0.6
15af	78.9	7.5	59.4	9.5	29.9	12.1	111.3	5.9	114.0	13.2	60.8	24.3	18.6	0.8

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A2780 drug-sensitive and OVCAR-5 drug-resistant cells were treated at a range of concentrations for 72 h. The cell viability of DMSO control was 100%, determined with the MTT assay.

CONCLUSIONS

Indolylmaleimides are an important type of privileged scaffold and thus novel synthetic pathways leading to such compounds could be significant for the preparation of molecules with diverse biological activities. We thus believe that the discovery of the rearrangement of 5-indolyl-3-pyrrolin-2-ones 12 into 4-indolyl-3-pyrrolin-2-ones 14 that could be performed in a one-pot manner without isolation of compounds 12 should find use in medicinal and/or bioorganic areas. Our methodology requires few steps and it does not utilize transition metals or protecting groups. Given the complexity and multistep nature of the transformations 10+11→14 (Figure 4), the obtained yields in the range of 30–66% for most of these transformations are acceptable. The biological relevance of the synthesized scaffolds is confirmed by the identification of antiproliferative activity in all three of the prepared series of compounds, i.e., 4-indolyl-3-pyrrolin-2-ones 14 (from Figure 4), 5-indolyl-3-pyrrolin-2-ones 12 (from Figure 7), and 5-hydroxy-4-indolyl-3-pyrrolin-2-ones 15. Compounds with antiproliferative action under both normoxia and hypoxia against MDA-MB-231 triple-negative breast cancer were identified and could serve as a starting point for more potent molecules. Another significant finding of this study is the comparable toxicity of compounds from each of the synthesized series on both treatment-sensitive and treatment-resistant ovarian cancer cell lines. While these initial biological evaluations highlight the potential of our indolylmaleimides as therapeutic agents, further studies will aim to decipher their mechanism of action and their therapeutic effects on more advanced tumor models.

EXPERIMENTAL SECTION

General Information

¹H and ¹³C{¹H} NMR spectra were recorded on a Bruker Avance-III spectrometer (400 or 101 MHz, respectively) equipped with BBO probe in CDCl₃ or DMSO-d₆ using TMS as an internal standard. High-resolution mass spectra were registered with a Bruker Maxis spectrometer (electrospray ionization, in MeCN solution, using HCO₂Na–HCO₂H for calibration). IR spectra were measured on an FT-IR spectrometer Shimadzu IR Affinity-1S equipped with an ATR sampling module. Melting points were measured with a Stuart SMP30 apparatus. MW-assisted reactions were conducted in G10 or G30 vials using an Anton Paar Monowave 300 reactor (Anton Paar GmbH, Austria, Serial Number 81552252) employing a constant temperature mode with temperature control by an IR sensor. Caution! The pressure in the reactor due to the presence of volatile solvents can reach 20 bar. Only certified pressure vials capable of withstanding such pressure should be used. Reaction progress and purity of isolated compounds were controlled by TLC on ALUGRAM Xtra SIL G UV 254 plates. Column chromatography was performed with Macherey Nagel Silica gel 60 (particle size: 0.063–0.20 mm). The indoles 10a, 10b, 10e, 10f, 10g and phenols 10c, 10d were purchased from commercial vendors. 5-Hydroxy-3-pyrrolin-2-one 11 was obtained using literature methods cited below, with the exception of compounds 11e, 11f, and 11k. These were prepared using General Procedure D and their complete characterization is provided following Procedure D. All reagents and solvents were purchased from commercial vendors and used as received.

General Procedure for the Preparation of 4-(1H-Indol-3-yl)-3,5-diaryl-1,5-dihydro-2H-pyrrol-2-ones (A)

A microwave reaction vial was charged with a desired 5-hydroxy-3,5-diaryl-1,5-dihydro-2H-pyrrol-2-one 11a–n (1 equiv, 1 mmol),³¹ indole 10a–g (1 equiv, 1 mmol), aluminum chloride (2 equiv, 2 mmol), and 1,4-dioxane (1 mL). The reaction mixture was stirred until the Friedel–Crafts reaction was complete, as TLC monitoring indicated. The sealed vial was then placed in the microwave reactor and heated at 130 °C for 40 min with temperature monitoring using an internal IR sensor. The reaction mixture was poured in H₂O (50 mL), treated with NH₄OH (0.5 mL of 25% aq solution), and extracted with EtOAc (4 × 20 mL). The final compounds were purified with column chromatography on silica gel using the hexane/EtOAc (1:2) solvent system.

4-(1H-Indol-3-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (14aa).

This compound was prepared by General Procedure A employing indole (10a, 117 mg, 1.00 mmol) and 5-hydroxy-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11a, 251 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 2:1, v/v). The title compound was obtained as a colorless solid, mp 146.8–148.5 °C (benzene), R_f 0.36 (EtOAc/hexane, 2:1, v/v). Yield 231 mg (0.66 mmol, 66%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.40 (s, 1H), 8.81 (s, 1H), 7.48 (d, J = 2.8 Hz, 1H), 7.40 (q, J = 1.9 Hz, 1H), 7.38 (d, J = 2.0 Hz, 1H), 7.31–7.27 (m, 2H), 7.26–7.23 (m, 4H), 7.21 (d, J = 7.8 Hz, 2H), 7.18–7.09 (m, 1H), 6.97–6.88 (m, 1H), 6.65–6.56 (m, 1H), 6.52 (d, J = 8.1 Hz, 1H), 5.78 (s, 1H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 172.3, 150.0, 139.8, 136.3, 133.3, 129.4 (2C), 128.4 (2C), 127.8 (2C), 127.6, 127.4 (2C), 127.4, 127.2, 127.1, 124.2, 121.4, 120.5, 119.1, 111.7, 108.4, 61.7. IR_νmax: 2884, 1786, 1672, 1557, 1520, 1497, 1420, 1312, 1244 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₄H₁₈N₂NaO [M + Na]⁺, 373.1311; found, 373.1319.

4-(1H-Indol-3-yl)-5-phenyl-3-(p-tolyl)-1,5-dihydro-2H-pyrrol-2-one (14ab).

This compound was prepared by General Procedure A employing indole (10a, 117 mg, 1.00 mmol) and 5-hydroxy-5-phenyl-3-(p-tolyl)-1,5-dihydro-2H-pyrrol-2-one³¹ (11b, 265 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 2:1, v/v). The title compound was obtained as a yellowish solid, mp 135.6–137.7 °C (benzene), R_f 0.65 (EtOAc/hexane, 2:1, v/v). Yield 222 mg (0.61 mmol, 61%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.36 (s, 1H), 8.77 (s, 1H), 7.44 (d, J = 2.7 Hz, 1H), 7.32–7.25 (m, 4H), 7.24–7.18 (m, 3H), 7.16–7.10 (m, 1H), 7.07–7.03 (m, 1H), 6.96–6.90 (m, 1H), 6.68–6.57 (m, 2H), 5.74 (s, 1H), 2.26 (s, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 172.4, 149.4, 139.9, 136.29 136.25, 130.3, 129.2 (2C), 128.4 (2C), 128.3 (2C), 127.6, 127.4 (2C), 127.3 126.9, 124.3, 121.4, 120.5, 119.1, 111.6, 108.5, 61.7, 20.9. IR_νmax: 2998, 1770, 1685, 1637, 1546, 1506, 1422, 1374, 1243 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₅H₂₀N₂NaO [M + Na]⁺, 387.1468; found, 387.1478.

3-(4-Ethylphenyl)-4-(1H-indol-3-yl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (14ac).

This compound was prepared by General Procedure A employing indole (10a, 117 mg, 1.00 mmol) and 3-(4-ethylphenyl)-5-hydroxy-5-phenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11c, 279 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 2:1, v/v). The title compound was obtained as a brown solid, mp 123.5–124.3 °C (benzene), R_f 0.27 (EtOAc/hexane, 2:1, v/v). Yield 207 mg (0.55 mmol, 55%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.37 (s, 1H), 8.79 (s, 1H), 7.37–7.32 (m, 2H), 7.32–7.28 (m, 2H), 7.28–7.19 (m, 3H), 7.17–7.13 (m, 1H), 7.14–7.07 (m, 2H), 6.99–6.90 (m, 1H), 6.67–6.56 (m, 1H), 5.77 (d, J = 1.3 Hz, 2H), 2.57 (q, J = 7.5 Hz, 2H), 1.15 (t, J = 7.6 Hz, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 172.5, 149.5, 142.7, 139.9, 136.3, 130.6, 129.3 (2C), 128.4 (2C), 127.5, 127.5 (2C), 127.4, 127.1 (2C), 126.9, 124.3, 121.4, 120.6, 119.1, 111.6, 108.5, 61.7, 28.0, 15.7. IR_νmax: 2998, 1770, 1685, 1637, 1546, 1506, 1422, 1374, 1243 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₆H₂₂N₂NaO [M + Na]⁺, 401.1624; found, 401.1636.

4-(1H-Indol-3-yl)-3,5-di-p-tolyl-1,5-dihydro-2H-pyrrol-2-one (14ad).

This compound was prepared by General Procedure A employing indole (10a, 117 mg, 1.00 mmol) and 5-hydroxy-3,5-di-p-tolyl-1,5-dihydro-2H-pyrrol-2-one³² (11d, 279 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 2:1, v/v). The title compound was obtained as a yellow solid, mp 139.5–140.9 °C (benzene), R_f 0.35 (EtOAc/hexane, 2:1, v/v). Yield 215 mg (0.57 mmol, 57%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.36 (s, 1H), 8.73 (s, 1H), 7.43 (d, J = 2.7 Hz, 1H), 7.29 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 8.1 Hz, 1H), 7.15 (d, J = 8.0 Hz, 2H), 7.05 (d, J = 7.9 Hz, 2H), 7.02 (s, 2H), 7.02–6.87 (m, 1H), 6.68–6.57 (m, 2H), 5.70 (d, J = 1.3 Hz, 1H), 2.26 (s, 3H), 2.16 (s, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 172.5, 149.6, 136.8, 136.7, 136.3, 136.3, 130.4, 129.2 (2C), 129.0 (2C), 128.4 (2C), 127.29 (2C), 127.26, 126.9, 124.3, 121.4, 120.6, 119.2, 111.7, 108.6, 61.5, 21.0, 20.7. IR_νmax: 2357, 1768, 1681, 1652, 1555, 1509, 1418, 1387, 1255 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₆H₂₂N₂NaO [M + Na]⁺, 401.1624; found, 401.1635.

4-(1H-Indol-3-yl)-3-(4-isopropylphenyl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (14ae).

This compound was prepared by General Procedure A employing indole (10a, 117 mg, 1.00 mmol) and 5-hydroxy-3-(4-isopropylphenyl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (11e, 293 mg, 1.00 mmol, synthesized by Procedure D). Purification was done by column chromatography (EtOAc/hexane, 2:1, v/v). The title compound was obtained as a yellowish solid, mp 190.1–192.2 °C (benzene), R_f 0.66 (EtOAc/hexane, 2:1, v/v). Yield 243 mg (0.62 mmol, 62%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.36 (s, 1H), 8.77 (s, 1H), 7.45 (d, J = 2.7 Hz, 1H), 7.34–7.26 (m, 4H), 7.25–7.19 (m, 3H), 7.17–7.10 (m, 3H), 6.95–6.90 (m, 1H), 6.62–6.54 (m, 1H), 6.51 (d, J = 8.0 Hz, 1H), 5.75 (s, 1H), 2.85 (p, J = 6.9 Hz, 1H), 1.18 (dd, J = 6.9, 2.8 Hz, 6H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 172.5, 149.6, 147.3, 139.9, 136.3, 130.8, 129.4 (2C), 128.4 (2C), 127.6, 127.5 (2C), 127.4, 127.0, 125.7 (2C), 124.3, 121.4, 120.7, 119.0, 111.6, 108.5, 61.7, 33.3, 23.9, 23.8. IR_νmax: 2852, 1765, 1685, 1633, 1557, 1505, 1454, 1388, 1214 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₇H₂₄N₂NaO [M + Na]⁺, 415.1781; found, 415.1790.

4-(1H-Indol-3-yl)-5-(naphthalen-2-yl)-3-(p-tolyl)-1,5-dihydro-2H-pyrrol-2-one (14af).

This compound was prepared by General Procedure A employing indole (10a, 117 mg, 1.00 mmol) and 5-hydroxy-5-(naphthalen-2-yl)-3-(p-tolyl)-1,5-dihydro-2H-pyrrol-2-one (11f, 315 mg, 1.00 mmol, synthesized by Procedure D). Purification was done by column chromatography (EtOAc/hexane, 2:1, v/v). The title compound was obtained as a yellowish solid, mp 155.9–158.3 °C (benzene), R_f 0.27 (EtOAc/hexane, 2:1, v/v). Yield 215 mg (0.52 mmol, 52%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.33 (d, J = 2.8 Hz, 1H), 8.89 (d, J = 1.4 Hz, 1H), 7.95 (s, 1H), 7.86–7.80 (m, 1H), 7.80–7.73 (m, 1H), 7.73 (d, J = 8.6 Hz, 1H), 7.50 (d, J = 2.8 Hz, 1H), 7.50–7.38 (m, 2H), 7.40–7.33 (m, 2H), 7.27 (dd, J = 8.6, 1.7 Hz, 1H), 7.20 (dt, J = 8.1, 0.9 Hz, 1H), 7.11–7.04 (m, 2H), 6.94–6.88 (m, 1H), 6.70–6.59 (m, 2H), 5.93 (d, J = 1.3 Hz, 1H), 2.28 (s, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 172.6, 149.4, 137.3, 136.3, 136.3, 132.7, 132.5, 130.3, 129.3 (2C), 128.4 (2C), 128.2, 127.6, 127.5 (2C), 127.1, 126.9, 126.3, 126.0, 124.3, 124.2, 121.4, 120.5, 119.2, 111.6, 108.5, 61.9, 21.0. IR_νmax: 2987, 1772, 1754, 1645, 1547, 1511, 1424, 1374, 1249 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₉H₂₂N₂NaO [M + Na]⁺, 437.1624; found, 437.1641.

4-(1H-Indol-3-yl)-3-(4-methoxyphenyl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (14ag).

This compound was prepared by General Procedure A employing indole (10a, 117 mg, 1.00 mmol) and 5-hydroxy-3-(4-methoxyphenyl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11g, 281 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 2:1, v/v). The title compound was obtained as a yellowish solid, mp 146.8–148.5 °C (benzene), R_f 0.36 (EtOAc/hexane, 2:1, v/v). Yield 140 mg (0.37 mmol, 37%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.38–11.33 (m, 1H), 8.77 (s, 1H), 7.44 (d, J = 2.7 Hz, 1H), 7.36 (d, J = 8.4 Hz, 2H), 7.31–7.25 (m, 2H), 7.25–7.18 (m, 3H), 7.17–7.11 (m, 1H), 6.97–6.92 (m, 1H), 6.81 (d, J = 8.4 Hz, 2H), 6.70–6.60 (m, 2H), 5.72 (s, 1H), 3.71 (s, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 172.6, 158.4, 148.8, 139.9, 136.3, 130.5 (2C), 128.4 (2C), 127.6, 127.4 (2C), 127.1, 126.8, 125.5, 124.3, 121.4, 120.6, 119.2, 113.3 (2C), 111.7, 108.6, 61.7, 55.0. IR_νmax: 2998, 2364, 1768, 1681, 1654, 1515, 1455, 1418, 1354 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₅H₂₀N₂NaO₂ [M + Na]⁺, 403.1417; found, 403.1429.

4-(1H-Indol-3-yl)-3,5-bis(4-methoxyphenyl)-1,5-dihydro-2H-pyrrol-2-one (14ah).

This compound was prepared by General Procedure A employing indole (10a, 117 mg, 1.00 mmol) and 5-hydroxy-3,5-bis(4-methoxyphenyl)-1,5-dihydro-2H-pyrrol-2-one³¹ (11h, 311 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 2:1, v/v). The title compound was obtained as a yellowish solid, mp 119.8–121.1 °C (benzene), R_f 0.27 (EtOAc/hexane, 2:1, v/v). Yield 143 mg (0.35 mmol, 35%). ¹H NMR (400 MHz, CDCl₃): δ 8.25 (s, 1H), 7.82–7.73 (m, 1H), 7.52–7.42 (m, 2H), 7.25–7.20 (m, 2H), 7.15–7.04 (m, 1H), 6.95–6.92 (m, 1H), 6.92–6.88 (m, 1H), 6.87–6.84 (m, 1H), 6.84–6.81 (m, 1H), 6.79 (q, J = 2.1 Hz, 2H), 6.78–6.73 (m, 1H), 6.27 (s, 1H), 5.41 (s, 1H), 3.76 (s, 6H); ¹³C{¹H} NMR (101 MHz, CDCl₃): δ 173.7, 159.8, 159.3, 148.6, 136.1, 130.8 (2C), 129.7, 129.1 (2C), 125.0, 124.9 (2C), 122.7, 121.5, 120.5, 114.4 (2C), 113.8 (2C), 111.2, 110.5, 62.9, 55.4, 55.3, 29.9. IR_νmax: 2357, 1768, 1681, 1652, 1555, 1509, 1418, 1387, 1255 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₆H₂₂N₂NaO₃ [M + Na]⁺, 433.1523; found, 433.1524.

5-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-4-(1H-indol-3-yl)-3-phenyl-1,5-dihydro-2H-pyrrol-2-one (14ai).

This compound was prepared by General Procedure A employing indole (10a, 117 mg, 1.00 mmol) and 5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-5-hydroxy-3-phenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11i, 309 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 2:1, v/v). The title compound was obtained as a yellow solid, mp 160.2–161.7 °C (benzene), R_f 0.37 (EtOAc/hexane, 2:1, v/v). Yield 196 mg (0.48 mmol, 48%). ¹H NMR (400 MHz, DMSO-d₆): 11.40 (s, 1H), 8.69 (s, 1H), 7.50 (s, 1H), 7.40–7.33 (m, 2H), 7.30–7.21 (m, 4H), 6.94 (t, J = 7.5 Hz, 1H), 6.77 (s, 1H), 6.76–6.67 (m, 2H), 6.61 (t, J = 7.5 Hz, 1H), 6.52 (d, J = 8.1 Hz, 1H), 5.67 (s, 1H), 4.13 (s, 4H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 172.1, 149.8, 143.0, 142.7, 136.4, 133.3, 132.7, 129.4 (2C), 127.7 (2C), 127.2, 127.16, 127.1, 124.2, 121.4, 120.5, 120.0, 119.1, 116.9, 116.0, 111.7, 108.4, 64.0, 63.9, 61.1. IR_νmax: 2998, 1770, 1681, 1633, 1556, 1511, 1424, 1374, 1249 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₆H₂₀N₂NaO₃ [M + Na]⁺, 431.1366; found, 431.1363.

4-(1H-Indol-3-yl)-5-(4-methoxyphenyl)-3-phenyl-1,5-dihydro-2H-pyrrol-2-one (14aj).

This compound was prepared by General Procedure A employing indole (10a, 117 mg, 1.00 mmol) and 5-hydroxy-5-(4-methoxyphenyl)-3-phenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11j, 281 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 2:1, v/v). The title compound was obtained as a brown solid, mp 118.3–120.6 °C (benzene), R_f 0.38 (EtOAc/hexane, 2:1, v/v). Yield 160 mg (0.42 mmol, 42%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.38 (d, J = 2.8 Hz, 1H), 8.76–8.71 (m, 1H), 7.44 (d, J = 2.8 Hz, 1H), 7.42–7.33 (m, 3H), 7.28–7.22 (m, 4H), 7.22–7.17 (m, 2H), 6.97–6.89 (m, 1H), 6.82–6.73 (m, 2H), 6.65–6.57 (m, 1H), 6.52 (d, J = 8.1 Hz, 1H), 3.64 (s, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 172.2, 158.6, 150.2, 136.3, 133.4, 131.5, 129.4 (2C), 128.5 (2C), 127.8 (2C), 127.2, 127.1, 127.1, 124.2, 121.4, 120.5, 119.12, 113.8 (2C), 111.7, 108.4, 61.2, 54.9. IR_νmax: 2998, 1754, 1654, 1634, 1557, 1517, 1488, 1378, 1285 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₅H₂₀N₂NaO₂ [M + Na]⁺, 403.1417; found, 403.1422.

4-(1H-Indol-3-yl)-5-phenyl-3-(2,4,5-trimethoxyphenyl)-1,5-dihydro-2H-pyrrol-2-one (14ak).

This compound was prepared by General Procedure A employing indole (10a, 117 mg, 1.00 mmol) and 5-hydroxy-5-phenyl-3-(2,4,5-trimethoxyphenyl)-1,5-dihydro-2H-pyrrol-2-one (11k, 341 mg, 1.00 mmol, synthesized by Procedure D). Purification was done by column chromatography (EtOAc). The title compound was obtained as a brown solid, mp 136.7–138.4 °C (benzene), R_f 0.42 (EtOAc). Yield 141 mg (0.32 mmol, 32%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.26 (d, J = 2.8 Hz, 1H), 8.59 (s, 1H), 7.42–7.32 (m, 2H), 7.34–7.23 (m, 2H), 7.26–7.19 (m, 3H), 7.18–7.09 (m, 1H), 6.99–6.90 (m, 2H), 6.77–6.65 (m, 2H), 5.83 (d, J = 1.3 Hz, 1H), 3.79 (s, 3H), 3.59 (s, 3H), 3.43 (s, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 172.7, 150.4, 149.4, 142.4, 140.3 (2C), 136.1 (2C), 128.4 (3C), 127.5 (2C), 127.4, 126.5, 124.9 (2C), 121.3, 120.3, 119.2, 114.5, 111.5, 98.9, 61.5, 56.4, 55.8 (2C). IR_νmax: 2364, 1772, 1685, 1652, 1556, 1517, 1457, 1374, 1249 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₇H₂₄N₂NaO₄ [M + Na]⁺, 463.1628; found, 463.1642.

3-(2-Fluorophenyl)-4-(1H-indol-3-yl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (14al).

This compound was prepared by General Procedure A employing indole (10a, 117 mg, 1.00 mmol) and 3-(2-fluorophenyl)-5-hydroxy-5-phenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11l, 269 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 2:1, v/v). The title compound was obtained as a yellowish solid, mp 151.6–152.1 °C (benzene), R_f 0.41 (EtOAc/hexane, 2:1, v/v). Yield 158 mg (0.43 mmol, 43%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.43 (s, 1H), 8.81 (s, 1H), 7.45 (d, J = 2.8 Hz, 1H), 7.40–7.32 (m, 4H), 7.27–7.21 (m, 3H), 7.20–7.10 (m, 3H), 6.98–6.90 (m, 1H), 6.70–6.59 (m, 2H), 5.91 (s, 1H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 171.8, 160.1 (d, J = 246.9 Hz), 152.5, 139.9, 136.3, 132.2 (d, J = 3.5 Hz), 129.7 (d, J = 8.1 Hz), 128.5 (2C), 128.3, 127.6, 127.4 (2C), 127.2, 124.6, 124.1 (d, J = 3.3 Hz), 122.7, 121.8 (d, J = 16.1 Hz), 121.5, 119.7, 119.4, 115.4 (d, J = 21.6 Hz), 111.8, 108.5, 68.2, 61.8; ¹⁹F NMR (376 MHz, DMSO-d₆): δ −112.34. IR_νmax: 3000, 1770, 1685, 1670, 1560, 1504, 1421, 1388, 1239 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₄H₁₇FN₂NaO [M + Na]⁺, 391.1217; found, 391.1226.

3-(4-Chlorophenyl)-4-(1H-indol-3-yl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (14am).

This compound was prepared by General Procedure A employing indole (10a, 117 mg, 1.00 mmol) and 3-(4-chlorophenyl)-5-hydroxy-5-phenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11m, 285 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 2:1, v/v). The title compound was obtained as a yellowish solid, mp 189.7–191.2 °C (benzene), R_f 0.29 (EtOAc/hexane, 2:1, v/v). Yield 223 mg (0.58 mmol, 58%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.45 (s, 1H), 8.87 (d, J = 1.3 Hz, 1H), 7.51 (d, J = 2.8 Hz, 1H), 7.45–7.37 (m, 2H), 7.35–7.25 (m, 4H), 7.28–7.17 (m, 3H), 7.18–7.09 (m, 1H), 7.02–6.90 (m, 1H), 6.72–6.63 (m, 1H), 6.54 (d, J = 8.1 Hz, 1H), 5.78 (d, J = 1.3 Hz, 1H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 172.1, 150.7, 139.6, 136.4, 132.1, 131.8, 131.1 (2C), 128.5 (2C), 127.9 (2C), 127.7, 127.4 (2C), 127.3, 126.0, 124.0, 121.6, 120.4, 119.4, 111.9, 108.1, 61.9. IR_νmax: 2968, 1774, 1652, 1634, 1557, 1505, 1418, 1374, 1055 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₄H₁₇ClN₂NaO [M + Na]⁺, 407.0922; found, 407.0929.

3-(4-Bromophenyl)-4-(1H-indol-3-yl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (14an).

This compound was prepared by General Procedure A employing indole (10a, 117 mg, 1.00 mmol) and 3-(4-bromophenyl)-5-hydroxy-5-phenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11n, 329 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 2:1, v/v). The title compound was obtained as a yellowish solid, mp 164.5–165.1 °C (benzene), R_f 0.36 (EtOAc/hexane, 2:1, v/v). Yield 227 mg (0.53 mmol, 53%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.45 (s, 1H), 8.87 (s, 1H), 7.51 (d, J = 2.8 Hz, 1H), 7.44 (d, J = 8.6 Hz, 2H), 7.39–7.33 (m, 2H), 7.31–7.24 (m, 3H), 7.24–7.18 (m, 2H), 7.17–7.09 (m, 1H), 7.00–6.91 (m, 1H), 6.72–6.64 (m, 1H), 6.56 (d, J = 8.1 Hz, 1H), 5.78 (s, 1H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 171.9, 150.6, 139.6, 136.4, 132.5, 131.3 (2C), 130.7 (2C), 128.4 (2C), 127.6, 127.4 (2C), 127.2, 126.0, 124.0, 121.5, 120.4, 120.3, 119.3, 111.8, 108.1, 61.8. IR_νmax: 2364, 1772, 1683, 1665, 1559, 1507, 1416, 1383, 1089 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₄H₁₇BrN₂NaO [M + Na]⁺, 451.0416; found, 451.0416.

4-(2-Methyl-1H-indol-3-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (14ba).

This compound was prepared by General Procedure A employing 2-methyl-1H-indole (10b, 131 mg, 1.00 mmol) and 5-hydroxy-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11a, 251 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 2:1, v/v). The title compound was obtained as a yellow solid, mp 147.4–150.0 °C (benzene), R_f 0.33 (EtOAc/hexane, 2:1, v/v). Yield 160 mg (0.44 mmol, 44%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.01 (s, 1H), 8.93 (s, 1H), 7.46 (s, 1H), 7.39–7.32 (m, 2H), 7.26–7.18 (m, 3H), 7.18–7.11 (m, 3H), 7.12–7.07 (m, 2H), 7.01–6.93 (m, 1H), 6.89 (t, J = 7.5 Hz, 1H), 1.72 (s, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 172.2, 151.4, 138.9 (2C), 135.4, 134.3, 133.1, 130.2, 128.7 (2C), 128.3 (2C), 127.9 (2C), 127.6, 127.10, 127.1 (2C), 120.6, 119.3, 118.6, 110.8, 105.0, 62.0, 12.3. IR_νmax: 2979, 1765, 1687, 1673, 1561, 1548, 1455, 1390, 1228 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₅H₂₀N₂NaO [M + Na]⁺, 387.1468; found, 387.1468.

4-(2-Hydroxynaphthalen-1-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (14ca).

This compound was prepared by General Procedure A employing naphthalen-2-ol (10c, 144 mg, 1.00 mmol) and 5-hydroxy-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11a, 251 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 2:1, v/v). The title compound was obtained as a brown solid, mp 190.1–192.2 °C (benzene), R_f 0.66 (EtOAc/hexane, 2:1, v/v). Yield 117 mg (0.31 mmol, 31%). ¹H NMR (400 MHz, DMSO-d₆): δ 9.88 (s, 1H), 9.02 (s, 1H), 7.71 (s, 1H), 7.55 (d, J = 8.9 Hz, 1H), 7.41 (d, J = 8.7 Hz, 1H), 7.36–7.35 (m, 2H), 7.33–7.30 (m, 3H), 7.30–7.28 (m, 1H), 7.22 (t, J = 7.5 Hz, 2H), 7.16–7.11 (m, 2H), 7.06–7.01 (m, 2H), 7.01–6.97 (m, 1H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 171.7, 156.3, 154.9, 138.5, 134.3, 132.1, 131.1, 129.8, 129.6 (2C), 128.5 (2C), 128.1 (2C), 127.9, 127.79, 127.76, 127.5 (2C), 127.1, 126.9, 126.3, 125.8, 119.1, 108.6, 61.4. IR_νmax: 2998, 1774, 1681, 1654, 1557, 1506, 1418, 1374, 1266 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₆H₁₉NNaO₂ [M + Na]⁺, 400.1308; found, 400.1318.

4-(2,4-Dihydroxyphenyl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (14da).

This compound was prepared by General Procedure A employing resorcinol (10d, 110 mg, 1.00 mmol) and 5-hydroxy-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11a, 251 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 2:1, v/v). The title compound was obtained as a yellowish solid, mp 137.2–139.1 °C (benzene), R_f 0.4 (EtOAc/hexane, 2:1, v/v). Yield 93 mg (0.27 mmol, 27%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.41 (s, 1H), 8.82 (s, 1H), 7.48 (d, J = 2.7 Hz, 1H), 7.42–7.37 (m, 2H), 7.30 (d, J = 7.1 Hz, 2H), 7.24 (dd, J = 8.1, 5.9 Hz, 5H), 7.14 (t, J = 7.2 Hz, 1H), 6.93 (t, J = 7.5 Hz, 1H), 6.61 (t, J = 7.5 Hz, 1H), 6.53 (d, J = 8.1 Hz, 1H), 5.78 (s, 1H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 172.1, 158.7, 156.0, 154.6, 138.7, 132.7, 131.2, 129.9, 129.1 (2C), 128.34, 128.30 (2C), 127.7 (2C), 127.5, 127.2 (2C), 111.2, 106.6, 102.6, 61.7. IR_νmax: 2996, 1775, 1756, 1687, 1650, 1555, 1416, 1372, 1241 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₂H₁₇NNaO₃ [M + Na]⁺, 366.1101; found, 366.1110.

4-(5-Chloro-2-methyl-1H-indol-3-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (14ea).

This compound was prepared by General Procedure A employing 5-chloro-2-methyl-1H-indole (10e, 165 mg, 1.00 mmol) and 5-hydroxy-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11a, 251 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:1, v/v). The title compound was obtained as a yellowish solid, mp 152.0–154.7 °C (benzene), R_f 0.67 (EtOAc/hexane, 1:1, v/v). Yield 131 mg (0.33 mmol, 33%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.22 (s, 1H), 8.96 (s, 1H), 7.39–7.30 (m, 3H), 7.28–7.20 (m, 3H), 7.20–7.16 (m, 2H), 7.16–7.13 (m, 2H), 7.12–7.09 (m, 2H), 6.98–6.91 (m, 1H), 5.89 (s, 1H), 1.76 (s, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 172.02, 150.61, 138.7, 136.2, 133.8, 132.9, 130.9, 128.7 (2C), 128.4 (2C), 128.1, 127.9 (2C), 127.7, 127.3, 127.0 (2C), 124.0, 120.6, 117.8, 112.1, 104.9, 62.0, 12.3. IR_νmax: 3257, 1677, 1656, 1489, 1469, 1434, 1316, 1232 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₅H₁₉ClN₂NaO [M + Na]⁺, 421.1078; found, 421.1083.

4-(5-Bromo-2-methyl-1H-indol-3-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (14fa).

This compound was prepared by General Procedure A employing 5-bromo-2-methyl-1H-indole (10f, 209 mg, 1.00 mmol) and 5-hydroxy-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11a, 251 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:1, v/v). The title compound was obtained as a brown solid, mp 156.9–159.1 °C (benzene), R_f 0.7 (EtOAc/hexane, 1:1, v/v). Yield 155 mg (0.35 mmol, 35%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.23 (s, 1H), 8.97 (s, 1H), 7.36–7.31 (m, 2H), 7.27–7.21 (m, 3H), 7.21–7.15 (m, 3H), 7.15–7.12 (m, 1H), 7.12–7.09 (m, 3H), 7.08–7.04 (m, 1H), 5.88 (s, 1H), 1.77 (s, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 172.0, 150.6, 138.7, 136.0, 134.1, 132.8, 131.0, 128.74, 128.70 (2C), 128.4 (2C), 127.9 (2C), 127.7, 127.3, 127.0 (2C), 123.1, 120.8, 112.6, 112.0, 104.8, 62.0, 12.3. IR_νmax: 3240, 1691, 1642, 1564, 1540, 1473, 1435, 1230, 1061 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₅H₁₉BrN₂NaO [M + Na]⁺, 465.0573; found, 465.05788.

4-(2-Methyl-5-nitro-1H-indol-3-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (14ga).

This compound was prepared by General Procedure A employing 2-methyl-5-nitro-1H-indole (10g, 176 mg, 1.00 mmol) and 5-hydroxy-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11a, 251 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:1, v/v). The title compound was obtained as a yellow solid, mp 169.5–172.3 °C (benzene), R_f 0.43 (EtOAc/hexane, 1:1, v/v). Yield 127 mg (0.31 mmol, 31%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.80 (s, 1H), 9.07 (s, 1H), 7.86 (dd, J = 8.9, 2.2 Hz, 1H), 7.36 (s, 2H), 7.35–7.31 (m, 2H), 7.26–7.19 (m, 3H), 7.16 (d, J = 6.5 Hz, 2H), 7.14–7.09 (m, 3H), 5.89 (s, 1H), 1.89 (s, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 171.8, 149.5, 140.9, 138.7, 138.4, 138.3, 132.4, 132.0, 128.7 (2C), 128.5 (2C), 128.0 (2C), 127.8, 127.5, 127.0 (2C), 126.2, 116.3, 115.4, 111.2, 107.4, 62.2, 12.3. IR_νmax: 3229, 2989, 1771, 1672, 1556, 1508, 1476, 1333, 1241 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₅H₁₉N₃NaO₃ [M + Na]⁺, 432.1319; found, 432.1327.

General Procedure for the Preparation of 5-(1H-Indol-3-yl)-3,5-diaryl-1,5-dihydro-2H-pyrrol-2-ones (B)

A reaction flask was charged with a desired 5-hydroxy-3,5-diaryl-1,5-dihydro-2H-pyrrol-2-one³¹ 11a–n (1 equiv, 1 mmol), indole 10a–g (1 equiv, 1 mmol), aluminum chloride (2 equiv, 2 mmol), and 1,4-dioxane (1 mL). The reaction mixture was stirred at rt until the Friedel–Crafts reaction was complete as TLC monitoring indicated. The reaction mixture was poured in H₂O (50 mL) and extracted with EtOAc (4 × 20 mL). The final compounds were purified with column chromatography on silica gel using the hexane/EtOAc (2:1) solvent system.

5-(1H-Indol-3-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (12aa).

This compound was prepared by General Procedure B employing indole (10a, 117 mg, 1.00 mmol) and 5-hydroxy-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11a, 251 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:2, v/v). The title compound was obtained as a colorless solid, mp 259.6–261.7 °C (EtOAc), R_f 0.25 (EtOAc/hexane, 1:2, v/v). Yield 329 mg (0.94 mmol, 94%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.08 (s, 1H), 9.63 (s, 1H), 8.22 (s, 1H), 8.06–8.00 (m, 2H), 7.52–7.47 (m, 2H), 7.43–7.37 (m, 3H), 7.37–7.35 (m, 2H), 7.35–7.31 (m, 2H), 7.31–7.26 (m, 1H), 7.12–7.07 (m, 1H), 7.07–7.02 (m, 1H), 6.93–6.84 (m, 1H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 170.8, 147.3, 142.0, 136.8, 131.9, 131.6, 128.33, 128.31 (2C), 128.3 (2C), 127.3, 127.0 (2C), 126.6 (2C), 125.0, 123.7, 121.3, 119.7, 118.8, 115.6, 111.8, 64.8. IR_νmax: 3174, 3050, 2996, 1772, 1654, 1492, 1419, 1243 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₄H₁₈N₂NaO [M + Na]⁺, 373.1311; found, 373.1325.

5-(1H-Indol-3-yl)-5-phenyl-3-(p-tolyl)-1,5-dihydro-2H-pyrrol-2-one (12ab).

This compound was prepared by General Procedure B employing indole (10a, 117 mg, 1.00 mmol) and 5-hydroxy-5-phenyl-3-(p-tolyl)-1,5-dihydro-2H-pyrrol-2-one³¹ (11b, 265 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:2, v/v). The title compound was obtained as a yellow solid, mp 233.3–235.4 °C (EtOAc), R_f 0.28 (EtOAc/hexane, 1:2, v/v). Yield 323 mg (0.89 mmol, 89%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.09 (s, 1H), 9.59 (s, 1H), 8.16 (s, 1H), 7.98–7.90 (m, 2H), 7.52–7.44 (m, 2H), 7.39–7.36 (m, 1H), 7.36–7.31 (m, 3H), 7.30–7.25 (m, 1H), 7.21 (d, J = 8.0 Hz, 2H), 7.07 (d, J = 2.4 Hz, 1H), 7.06–7.02 (m, 1H), 6.92–6.83 (m, 1H), 2.31 (s, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 170.9, 146.3, 142.1, 137.7, 136.8, 131.7, 128.9 (2C), 128.8, 128.3 (2C), 127.3, 126.9 (2C), 126.6 (2C), 125.0, 123.6, 121.3, 119.7, 118.8, 115.8, 111.8, 64.8, 20.9. IR_νmax: 3154, 3043, 2996, 1770, 1668, 1558, 1506, 1243, 1061 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₅H₂₀N₂NaO [M + Na]⁺, 387.1468; found, 387.1476.

3-(4-Ethylphenyl)-5-(1H-indol-3-yl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (12ac).

This compound was prepared by General Procedure B employing indole (10a, 117 mg, 1.00 mmol) and 3-(4-ethylphenyl)-5-hydroxy-5-phenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11c, 279 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:2, v/v). The title compound was obtained as a colorless solid, mp 256.4–257.3 °C (EtOAc), R_f 0.26 (EtOAc/hexane, 1:2, v/v). Yield 328 mg (0.87 mmol, 87%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.07 (s, 1H), 9.58 (s, 1H), 8.15 (s, 1H), 7.95 (d, J = 8.1 Hz, 2H), 7.52–7.45 (m, 2H), 7.38–7.36 (m, 1H), 7.36–7.26 (m, 4H), 7.24 (d, J = 8.0 Hz, 2H), 7.07 (d, J = 2.6 Hz, 1H), 7.06–7.03 (m, 1H), 6.91–6.85 (m, 1H), 2.61 (q, J = 7.6 Hz, 2H), 1.18 (t, J = 7.6 Hz, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 170.9, 146.4, 144.1, 142.1, 136.8, 131.8, 129.1, 128.3 (2C), 127.7 (2C), 127.25, 127.0 (2C), 126.6 (2C), 125.0, 123.6, 121.3, 119.7, 118.8, 115.8, 111.7, 64.8, 28.0, 15.6. IR_νmax: 3194, 2995, 2953, 1770, 1665, 1615, 1456, 1242, 1191 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₆H₂₂N₂NaO [M + Na]⁺, 401.1624; found, 401.1632.

5-(1H-Indol-3-yl)-3,5-di-p-tolyl-1,5-dihydro-2H-pyrrol-2-one (12ad).

This compound was prepared by General Procedure B employing indole (10a, 117 mg, 1.00 mmol) and 5-hydroxy-3,5-di-p-tolyl-1,5-dihydro-2H-pyrrol-2-one³² (11d, 279 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:2, v/v). The title compound was obtained as a yellow solid, mp 234.7–235.1 °C (EtOAc), R_f 0.24 (EtOAc/hexane, 1:2, v/v). Yield 332 mg (0.88 mmol, 88%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.08 (s, 1H), 9.54 (s, 1H), 8.12 (s, 1H), 7.97–7.90 (m, 2H), 7.38–7.34 (m, 3H), 7.32 (d, J = 8.1 Hz, 1H), 7.20 (d, J = 8.1 Hz, 2H), 7.15 (d, J = 8.0 Hz, 2H), 7.07 (d, J = 2.4 Hz, 1H), 7.06–7.02 (m, 1H), 6.90–6.85 (m, 1H), 2.31 (s, 3H), 2.28 (s, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 170.9, 146.4, 139.1, 137.7, 136.8, 136.4, 131.6, 128.9 (2C), 128.8 (2C), 126.9 (2C), 126.5 (2C), 125.1, 123.6, 121.2, 119.7, 118.7, 115.9, 111.7, 64.5, 20.9, 20.6 (one quaternary carbon missing). IR_νmax: 3359, 2996, 2184, 1775, 1671, 1556, 1455, 1244, 1186 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₆H₂₂N₂NaO [M + Na]⁺, 401.1624; found, 401.1631.

5-(1H-Indol-3-yl)-3-(4-isopropylphenyl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (12ae).

This compound was prepared by General Procedure B employing indole (10a, 117 mg, 1.00 mmol) and 5-hydroxy-3-(4-isopropylphenyl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (11e, 293 mg, 1.00 mmol, synthesized by Procedure D). Purification was done by column chromatography (EtOAc/hexane, 1:2, v/v). The title compound was obtained as a colorless solid, mp 241.6–242.1 °C (EtOAc), R_f 0.31 (EtOAc/hexane, 1:2, v/v). Yield 361 mg (0.92 mmol, 92%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.07 (s, 1H), 9.58 (s, 1H), 8.14 (s, 1H), 7.98–7.90 (m, 2H), 7.52–7.45 (m, 2H), 7.39–7.34 (m, 2H), 7.34–7.30 (m, 2H), 7.29–7.25 (m, 3H), 7.10–7.01 (m, 2H), 6.92–6.84 (m, 1H), 2.89 (p, J = 6.9 Hz, 1H), 1.20 (d, J = 6.8 Hz, 6H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 170.9, 148.6, 146.5, 142.1, 136.8, 131.9, 129.2, 128.3 (2C), 127.3, 127.1 (2C), 126.6 (2C), 126.2 (2C), 125.03, 123.7, 121.3, 119.7, 118.8, 115.7, 111.7, 64.8, 33.3, 23.8 (2C). IR_νmax: 3092, 2987, 1662, 1637, 1536, 1507, 1424, 1337 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₇H₂₄N₂NaO [M + Na]⁺, 415.1781; found, 415.1786.

5-(1H-Indol-3-yl)-5-(naphthalen-2-yl)-3-(p-tolyl)-1,5-dihydro-2H-pyrrol-2-one (12af).

This compound was prepared by General Procedure B employing indole (10a, 117 mg, 1.00 mmol) and 5-hydroxy-5-(naphthalen-2-yl)-3-(p-tolyl)-1,5-dihydro-2H-pyrrol-2-one (11f, 315 mg, 1.00 mmol, synthesized by Procedure D). Purification was done by column chromatography (EtOAc/hexane, 1:2, v/v). The title compound was obtained as a yellow solid, mp 259.5–261.0 °C (EtOAc), R_f 0.26 (EtOAc/hexane, 1:2, v/v). Yield 373 mg (0.90 mmol, 90%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.11 (d, J = 2.7 Hz, 1H), 9.70 (d, J = 1.9 Hz, 1H), 8.27 (d, J = 1.8 Hz, 1H), 8.04 (d, J = 1.9 Hz, 1H), 8.00–7.94 (m, 2H), 7.92–7.83 (m, 3H), 7.60 (dd, J = 8.7, 1.9 Hz, 1H), 7.55–7.46 (m, 2H), 7.38 (d, J = 8.1 Hz, 1H), 7.33 (d, J = 8.0 Hz, 1H), 7.22 (d, J = 8.1 Hz, 2H), 7.15 (d, J = 2.6 Hz, 1H), 7.05 (ddd, J = 8.2, 7.0, 1.1 Hz, 1H), 6.88–6.81 (m, 1H), 2.32 (s, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 171.0, 146.2, 139.7, 137.8, 136.8, 132.7, 132.1, 131.96, 128.9 (2C), 128.8, 128.0, 127.8, 127.5, 127.0 (2C), 126.4, 126.2, 125.5, 125.1, 124.4, 123.7, 121.3, 119.6, 118.8, 115.6, 111.8, 64.9, 20.9. IR_νmax: 3086, 2987, 1685, 1674, 1635, 1509, 1415, 1339 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₉H₂₂N₂NaO [M + Na]⁺, 437.1624; found, 437.1635.

5-(1H-Indol-3-yl)-3-(4-methoxyphenyl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (12ag).

This compound was prepared by General Procedure B employing indole (10a, 117 mg, 1.00 mmol) and 5-hydroxy-3-(4-methoxyphenyl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11g, 281 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:1, v/v). The title compound was obtained as a colorless solid, mp 258.0–259.5 °C (EtOAc), R_f 0.57 (EtOAc/hexane, 1:1, v/v). Yield 292 mg (0.77 mmol, 77%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.07 (s, 1H), 9.57 (s, 1H), 8.08 (s, 1H), 8.05–7.97 (m, 2H), 7.52–7.44 (m, 2H), 7.39–7.36 (m, 1H), 7.36–7.31 (m, 3H), 7.30–7.25 (m, 1H), 7.07 (d, J = 2.3 Hz, 1H), 7.07–7.02 (m, 1H), 6.98–6.94 (m, 2H), 6.91–6.85 (m, 1H), 3.77 (s, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 171.1, 159.3, 145.1, 142.2, 136.8, 131.3, 128.4 (2C), 128.2 (2C), 127.2, 126.6 (2C), 125.1, 124.1, 123.6, 121.3, 119.7, 118.7, 115.9, 113.7 (2C), 111.7, 64.7, 55.1. IR_νmax: 3191, 2995, 1770, 1671, 1654, 1504, 1418, 1340, 1255 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₅H₂₀N₂NaO₂ [M + Na]⁺, 403.1417; found, 403.1424.

5-(1H-Indol-3-yl)-3,5-bis(4-methoxyphenyl)-1,5-dihydro-2H-pyrrol-2-one (12ah).

This compound was prepared by General Procedure B employing indole (10a, 117 mg, 1.00 mmol) and 5-hydroxy-3,5-bis(4-methoxyphenyl)-1,5-dihydro-2H-pyrrol-2-one³¹ (11h, 311 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:1, v/v). The title compound was obtained as a yellow solid, mp 225.1–226.0 °C (EtOAc), R_f 0.49 (EtOAc/hexane, 1:1, v/v). Yield 282 mg (0.69 mmol, 69%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.03 (s, 1H), 9.49 (s, 1H), 8.03 (s, 1H), 8.00 (d, J = 8.6 Hz, 2H), 7.39–7.34 (m, 3H), 7.31 (d, J = 8.0 Hz, 1H), 7.08–7.02 (m, 2H), 6.95 (d, J = 8.5 Hz, 2H), 6.92–6.85 (m, 3H), 3.77 (s, 3H), 3.73 (s, 3H).; ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 171.0, 159.3, 158.3, 145.3, 136.8, 134.1, 131.1, 128.3 (2C), 127.8 (2C), 125.1, 124.2, 123.5, 121.2, 119.8, 118.7, 116.1, 113.7 (2C), 113.5 (2C), 111.7, 64.2, 55.14, 55.1. v_νmax: 3071, 2989, 1767, 1758, 1653, 1560, 1508, 1434, 1248 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₆H₂₂N₂NaO₃ [M + Na]⁺, 433.1523; found, 433.1524.

5-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-5-(1H-indol-3-yl)-3-phenyl-1,5-dihydro-2H-pyrrol-2-one (12ai).

This compound was prepared by General Procedure B employing indole (10a, 117 mg, 1.00 mmol) and 5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-5-hydroxy-3-phenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11i, 309 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:1, v/v). The title compound was obtained as a yellow solid, mp 143.2–144.1 °C (EtOAc), R_f 0.51 (EtOAc/hexane, 1:1, v/v). Yield 290 mg (0.71 mmol, 71%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.06 (s, 1H), 9.53 (s, 1H), 8.17 (s, 1H), 8.05–7.98 (m, 2H), 7.43–7.30 (m, 5H), 7.10 (d, J = 2.6 Hz, 1H), 7.09–7.03 (m, 1H), 6.94 (d, J = 1.6 Hz, 1H), 6.92 (d, J = 1.9 Hz, 1H), 6.91–6.85 (m, 1H), 6.84–6.80 (m, 1H), 4.21 (s, 4H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 170.7, 147.4, 142.9, 142.5, 136.8, 135.0, 131.7, 131,6, 128.3 (3C), 127.0 (2C), 125.0, 123.6, 121.3, 119.7, 119.5, 118.8, 116.7, 115.7, 115.6, 111.7, 64.3, 64.1 (2C). IR_νmax: 3077, 2993, 1681, 1633, 1556, 1486, 1283, 1258, 1125 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₆H₂₀N₂NaO₃ [M + Na]⁺, 431.1366; found, 431.1369.

5-(1H-Indol-3-yl)-5-(4-methoxyphenyl)-3-phenyl-1,5-dihydro-2H-pyrrol-2-one (12aj).

This compound was prepared by General Procedure B employing indole (10a, 117 mg, 1.00 mmol) and 5-hydroxy-5-(4-methoxyphenyl)-3-phenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11j, 281 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:1, v/v). The title compound was obtained as a brown solid, mp 153.7–154.2 °C (EtOAc), R_f 0.27 (EtOAc/hexane, 1:1, v/v). Yield 300 mg (0.79 mmol, 79%). ¹H NMR (400 MHz, DMSO-d₆): δ 10.22 (d, J = 2.6 Hz, 1H), 8.71 (d, J = 1.9 Hz, 1H), 7.33 (d, J = 1.8 Hz, 1H), 7.21–7.14 (m, 2H), 6.58–6.54 (m, 2H), 6.54–6.52 (m, 2H), 6.52–6.46 (m, 3H), 6.23 (d, J = 2.4 Hz, 1H), 6.24–6.17 (m, 1H), 6.12–5.98 (m, 3H), 2.89 (s, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 170.8, 158.4, 147.5, 136.8, 133.9, 131.7, 131.6, 128.3 (3C), 127.8 (2C), 127.0 (2C), 125.1, 123.6, 121.3, 119.7, 118.7, 115.9, 113.6 (2C), 111.7, 64.4, 55.1. IR_νmax: 3077, 2993, 1681, 1633, 1556, 1486, 1283, 1258, 1125 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₅H₂₀N₂NaO₂ [M + Na]⁺, 403.1414; found, 403.1425.

5-(1H-Indol-3-yl)-5-phenyl-3-(2,4,5-trimethoxyphenyl)-1,5-dihydro-2H-pyrrol-2-one (12ak).

This compound was prepared by General Procedure B employing indole (10a, 117 mg, 1.00 mmol) and 5-hydroxy-5-phenyl-3-(2,4,5-trimethoxyphenyl)-1,5-dihydro-2H-pyrrol-2-one (11k, 341 mg, 1.00 mmol, synthesized by Procedure D). Purification was done by column chromatography (EtOAc/hexane, 1:1, v/v). The title compound was obtained as a colorless solid, mp 233.5–234.1 °C (EtOAc), R_f 0.24 (EtOAc/hexane, 1:1, v/v). Yield 277 mg (0.63 mmol, 63%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.05 (d, J = 2.8 Hz, 1H), 9.52 (s, 1H), 8.05 (s, 1H), 8.03 (s, 1H), 7.48–7.43 (m, 2H), 7.39–7.32 (m, 3H), 7.31–7.25 (m, 2H), 7.08–7.05 (m, 1H), 7.04 (d, J = 2.6 Hz, 1H), 6.91–6.85 (m, 1H), 6.74 (s, 1H), 3.83 (s, 6H), 3.71 (s, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 171.6, 153.0, 149.5, 148.3, 142.3, 141.9, 136.8, 128.3 (2C), 127.3, 127.2, 126.6 (2C), 125.1, 123.6, 121.3, 119.7, 118.7, 115.9, 113.6, 111.8, 111.6, 97.9, 64.6, 56.3, 56.2, 55.7. IR_νmax: 3057, 2997, 1675, 1519, 1467, 1395, 1339, 1245, 1140 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₇H₂₄N₂NaO₄ [M + Na]⁺, 463.1628; found, 463.1629.

3-(2-Fluorophenyl)-5-(1H-indol-3-yl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (12al).

This compound was prepared by General Procedure B employing indole (10a, 117 mg, 1.00 mmol) and 3-(2-fluorophenyl)-5-hydroxy-5-phenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11l, 269 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:2, v/v). The title compound was obtained as a colorless solid, mp 202.3–203.6 °C (EtOAc), R_f 0.23 (EtOAc/hexane, 1:2, v/v). Yield 294 mg (0.80 mmol, 80%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.11 (s, 1H), 9.71 (s, 1H), 8.13–8.08 (m, 1H), 8.07 (t, J = 2.0 Hz, 1H), 7.49 (dd, J = 7.6, 1.8 Hz, 2H), 7.45–7.40 (m, 1H), 7.39–7.36 (m, 2H), 7.35–7.31 (m, 1H), 7.31–7.23 (m, 4H), 7.11–7.02 (m, 2H), 6.92–6.86 (m, 1H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 170.3, 160.2 (d, J = 248.7 Hz), 151.0 (d, J = 8.8 Hz), 141.6, 136.8, 130.2 (d, J = 3.0 Hz), 130.1 (d, J = 2.6 Hz), 128.4 (2C), 127.4, 126.9, 126.6 (2C), 125.0, 124.2 (d, J = 3.3 Hz), 123.7, 121.3, 119.6, 119.4 (d, J = 12.7 Hz), 118.8, 115.7 (d, J = 21.6 Hz), 115.2, 111.8, 65.5; ¹⁹F NMR (376 MHz, DMSO-d₆): δ −113.23. IR_νmax: 3084, 2976, 1751, 1735, 1683, 1633, 1536, 1517, 1457, 1419 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₄H₁₇FN₂NaO [M + Na]⁺, 391.1217; found, 391.1223.

3-(4-Chlorophenyl)-5-(1H-indol-3-yl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (12am).

This compound was prepared by General Procedure B employing indole (10a, 117 mg, 1.00 mmol) and 3-(4-chlorophenyl)-5-hydroxy-5-phenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11m, 285 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:2, v/v). The title compound was obtained as a brown solid, mp 256.7–257.1 °C (EtOAc), R_f 0.26 (EtOAc/hexane, 1:2, v/v). Yield 322 mg (0.84 mmol, 84%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.09 (s, 1H), 9.69 (s, 1H), 8.32 (s, 1H), 8.14–8.07 (m, 2H), 7.50–7.47 (m, 2H), 7.47–7.45 (m, 2H), 7.38 (d, J = 3.5 Hz, 1H), 7.37–7.34 (m, 1H), 7.33 (d, J = 6.2 Hz, 1H), 7.31–7.26 (m, 2H), 7.10 (d, J = 2.6 Hz, 1H), 7.08–7.03 (m, 1H), 6.92–6.84 (m, 1H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 170.5, 148.0, 141.8, 136.8, 133.0, 130.6, 130.48, 128.8 (2C), 128.4 (2C), 128.3 (2C), 127.4, 126.6 (2C), 125.0, 123.7, 121.3, 119.6, 118.8, 115.4, 111.8, 64.9. IR_νmax: 3184, 2996, 2021, 1770, 1672, 1614, 1556, 1419, 1241 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₄H₁₇ClN₂NaO [M + Na]⁺, 407.0922; found, 407.0922.

3-(4-Bromophenyl)-5-(1H-indol-3-yl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (12an).

This compound was prepared by General Procedure B employing indole (10a, 117 mg, 1.00 mmol) and 3-(4-bromophenyl)-5-hydroxy-5-phenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11n, 329 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:2, v/v). The title compound was obtained as a colorless solid, mp 248.4–249.0 °C (EtOAc), R_f 0.29 (EtOAc/hexane, 1:2, v/v). Yield 338 mg (0.79 mmol, 79%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.10 (s, 1H), 9.69 (s, 1H), 8.33 (s, 1H), 8.03 (d, J = 8.5 Hz, 2H), 7.61 (d, J = 8.4 Hz, 2H), 7.48 (d, J = 8.1 Hz, 2H), 7.39–7.33 (m, 3H), 7.33–7.26 (m, 2H), 7.12–7.02 (m, 2H), 6.88 (t, J = 7.5 Hz, 1H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 170.5, 148.0, 141.7, 136.8, 131.3 (2C), 130.8, 130.7, 129.1 (2C), 128.3 (2C), 127.4, 126.6 (2C), 125.0, 123.7, 121.7, 121.3, 119.6, 118.80, 115.4, 111.8, 65.0. IR_νmax: 3069, 2996, 1769, 1669, 1556, 1506, 1457, 1240 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₄H₁₇BrN₂NaO [M + Na]⁺, 451.0416; found, 451.0421.

5-(2-Methyl-1H-indol-3-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (12ba).

This compound was prepared by General Procedure B employing 2-methyl-1H-indole (10b, 131 mg, 1.00 mmol) and 5-hydroxy-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11a, 251 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:1, v/v). The title compound was obtained as a colorless solid, mp 213.1–215.6 °C (EtOAc), lit 183.4–185.6 °C (EtOAc),⁹ R_f 0.46 (EtOAc/hexane, 1:1, v/v). Yield 277 mg (0.76 mmol, 76%). ¹H NMR (400 MHz, DMSO-d₆): δ 10.99 (s, 1H), 9.44 (s, 1H), 8.14 (s, 1H), 8.07–8.02 (m, 2H), 7.48–7.41 (m, 2H), 7.41–7.34 (m, 4H), 7.34 (d, J = 2.5 Hz, 1H), 7.32–7.28 (m, 1H), 7.27–7.22 (m, 1H), 6.99 (d, J = 8.1 Hz, 1H), 6.97–6.92 (m, 1H), 6.79–6.73 (m, 1H), 2.13 (s, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 170.8, 148.0, 142.9, 134.9, 133.2, 131.7, 130.9, 128.42 (2C), 128.37 (2C), 128.3, 127.3, 127.0, 126.9 (2C), 126.6 (2C), 120.1, 119.4, 118.5, 110.6, 109.6, 65.8, 13.6. IR_νmax: 3190, 2945, 1723, 1655, 1521, 1469, 1370, 1249 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₅H₂₀N₂NaO [M + Na]⁺, 387.1468; found, 387.1471.

5-(2-Hydroxynaphthalen-1-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (12ca).

This compound was prepared by General Procedure B employing naphthalen-2-ol (10c, 144 mg, 1.00 mmol) and 5-hydroxy-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11a, 251 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:2, v/v). The title compound was obtained as a yellow solid, mp 149.1–151.2 °C (EtOAc), R_f 0.24 (EtOAc/hexane, 1:2, v/v). Yield 218 mg (0.58 mmol, 58%). ¹H NMR (400 MHz, DMSO-d₆): δ 9.85 (d, J = 1.9 Hz, 1H), 9.79 (s, 1H), 8.39 (d, J = 1.8 Hz, 1H), 8.07–7.99 (m, 2H), 7.78 (d, J = 1.9 Hz, 1H), 7.75–7.68 (m, 1H), 7.66 (d, J = 8.7 Hz, 1H), 7.45–7.41 (m, 2H), 7.41–7.39 (m, 2H), 7.39–7.33 (m, 4H), 7.33–7.25 (m, 1H), 7.08 (d, J = 7.8 Hz, 2H).; ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 170.7, 155.7, 147.2, 142.4, 136.4, 133.7, 132.2, 131.5, 129.5, 128.5 (3C), 128.3 (2C), 127.4, 127.1, 127.1 (2C), 126.8 (2C), 126.4, 125.5, 124.7, 119.1, 108.5, 68.5. IR_νmax: 3077, 2990, 1770, 1677, 1602, 1511, 1445, 1239 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₆H₁₉NNaO₂ [M + Na]⁺, 400.1308; found, 400.1315.

5-(2,4-Dihydroxyphenyl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (12da).

This compound was prepared by General Procedure B employing resorcinol (10d, 110 mg, 1.00 mmol) and 5-hydroxy-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11a, 251 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:1, v/v). The title compound was obtained as a colorless solid, mp 152.1–152.0 °C (EtOAc), R_f 0.27 (EtOAc/hexane, 1:1, v/v). Yield 243 mg (0.71 mmol, 71%). ¹H NMR (400 MHz, DMSO-d₆): δ 9.55 (s, 1H), 9.32 (s, 1H), 9.06 (s, 1H), 8.19 (s, 1H), 7.96 (d, J = 7.5 Hz, 2H), 7.43–7.33 (m, 3H), 7.35–7.16 (m, 5H), 6.31–6.21 (m, 2H), 3.56 (s, 1H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 170.4, 158.1, 155.7, 146.8, 142.6, 131.7, 131.7, 128.3 (2C), 128.3, 128.1, 128.0 (2C), 126.9 (2C), 126.8, 126.0 (2C), 118.4, 105.7, 103.2, 66.4. IR_νmax: 3048, 2998, 1775, 1682, 1560, 1506, 1415, 1143 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₂H₁₇NNaO₃ [M + Na]⁺, 366.1101; found, 366.1098.

5-(5-Chloro-2-methyl-1H-indol-3-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (12ea).

This compound was prepared by General Procedure B employing 5-chloro-2-methyl-1H-indole (10e, 165 mg, 1.00 mmol) and 5-hydroxy-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11a, 251 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:1, v/v). The title compound was obtained as a yellow solid, mp 221.1–223.6 °C (EtOAc), R_f 0.66 (EtOAc/hexane, 1:1, v/v). Yield 187 mg (0.47 mmol, 47%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.24 (s, 1H), 9.50 (d, J = 1.9 Hz, 1H), 8.15 (d, J = 1.8 Hz, 1H), 8.08–8.00 (m, 2H), 7.46–7.42 (m, 3H), 7.42–7.38 (m, 2H), 7.38–7.34 (m, 2H), 7.34–7.29 (m, 1H), 7.26 (d, J = 8.5 Hz, 1H), 6.95 (dd, J = 8.5, 2.0 Hz, 1H), 6.92 (d, J = 2.0 Hz, 1H), 2.14 (s, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 170.8, 147.7, 142.5, 135.2, 133.4, 131.6, 131.1, 128.6 (2C), 128.4 (3C), 128.0, 127.5, 127.0 (2C), 126.6 (2C), 123.1, 120.0, 118.7, 112.0, 109.7, 65.5, 13.7. IR_νmax: 2996, 1774, 1672, 1654, 1535, 1417, 1243, 1127 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₅H₁₉ClN₂NaO [M + Na]⁺, 421.1078; found, 421.1091.

5-(5-Bromo-2-methyl-1H-indol-3-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (12fa).

This compound was prepared by General Procedure B employing 5-bromo-2-methyl-1H-indole (10f, 209 mg, 1.00 mmol) and 5-hydroxy-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11a, 251 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:1, v/v). The title compound was obtained as a colorless solid, mp 250.0–251.2 °C (EtOAc), R_f 0.65 (EtOAc/hexane, 1:1, v/v). Yield 230 mg (0.52 mmol, 52%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.25 (s, 1H), 9.51 (s, 1H), 8.15 (s, 1H), 8.07–8.02 (m, 2H), 7.47–7.41 (m, 3H), 7.42–7.38 (m, 2H), 7.38–7.34 (m, 2H), 7.34–7.31 (m, 1H), 7.24–7.20 (m, 1H), 7.09–7.05 (m, 2H), 2.14 (s, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 170.7, 147.7, 142.5, 135.1, 133.6, 131.6, 131.1, 128.7, 128.5 (2C), 128.4 (3C), 127.5, 127.0 (2C), 126.6 (2C), 122.5, 121.7, 112.5, 111.2, 109.6, 65.5, 13.7. IR_νmax: 3332, 3003, 1768, 1654, 1555, 1414, 1258, 1120, 1058 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₅H₁₉BrN₂NaO [M + Na]⁺, 465.0573; found, 465.05797.

5-(2-Methyl-5-nitro-1H-indol-3-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (12ga).

This compound was prepared by General Procedure B employing 2-methyl-5-nitro-1H-indole (10g, 176 mg, 1.00 mmol) and 5-hydroxy-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one³¹ (11a, 251 mg, 1.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:1, v/v). The title compound was obtained as a yellow solid, mp 264.3–266.2 °C (EtOAc), R_f 0.43 (EtOAc/hexane, 1:1, v/v). Yield 168 mg (0.41 mmol, 41%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.82 (s, 1H), 9.64 (s, 1H), 8.21 (s, 1H), 8.10–8.03 (m, 2H), 7.94 (s, 1H), 7.92–7.85 (m, 1H), 7.48 (d, J = 7.2 Hz, 2H), 7.45–7.42 (m, 1H), 7.42–7.39 (m, 3H), 7.38–7.31 (m, 3H), 2.19 (s, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 170.8, 147.4, 142.2, 140.2, 138.3, 137.6, 131.53, 131.5, 128.7 (2C), 128.5, 128.4 (2C), 127.7, 127.1 (2C), 126.6 (2C), 126.2, 116.6, 115.8, 112.5, 111.0, 65.3, 13.7. IR_νmax: 3296, 2998, 1777, 1672, 1548, 1470, 1325, 1247, 1074 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₅H₁₉N₃NaO₃ [M + Na]⁺, 432.1319; found, 432.1331.

General Procedure for the Preparation of 5-Hydroxy-4-(1H-indol-3-yl)-3,5-diaryl-1,5-dihydro-2H-pyrrol-2-ones (C)

A 5 mL round-bottom reaction flask was charged with a desired 4-indolyl-3,5-diaryl-3-pyrrolin-2-one 14 (1 equiv, 0.25 mmol), selenium dioxide (2 equiv, 0.055 g, 0.5 mmol), and MeCN (0.5 mL), and the mixture was stirred under reflux for 2 h using a heating mantle as a heat source. The reaction was monitored by TLC. The reaction mixture was poured in H₂O (50 mL) and extracted with EtOAc (4 × 20 mL). The final compounds were purified with column chromatography on silica gel using the hexane/EtOAc (1:1) solvent system.

5-Hydroxy-4-(1H-indol-3-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (15aa).

This compound was prepared by General Procedure C employing 4-(1H-indol-3-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (14aa, 88 mg, 0.25 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:1, v/v). The title compound was obtained as a yellowish solid, mp 148.1–150.4 °C (benzene), R_f 0.32 (EtOAc/hexane, 1:1, v/v). Yield 77 mg (0.21 mmol, 82%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.31 (s, 1H), 8.94 (s, 1H), 7.52–7.47 (m, 2H), 7.42–7.37 (m, 3H), 7.27 (d, J = 7.5 Hz, 2H), 7.25–7.21 (m, 4H), 7.19 (d, J = 7.3 Hz, 1H), 6.93–6.87 (m, 2H), 6.53 (t, J = 7.6 Hz, 1H), 6.36 (d, J = 8.2 Hz, 1H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 171.0, 151.2, 142.2, 135.9, 133.2, 129.5 (2C), 128.0 (2C), 127.7 (2C), 127.4, 127.3, 127.2, 125.9, 125.6 (2C), 124.7, 121.2, 120.8, 118.9, 111.6, 107.2, 88.2. IR_νmax: 2994, 1772, 1685, 1650, 1559, 1503, 1420, 1390, 1240 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₄H₁₈N₂NaO₂ [M + Na]⁺, 389.1260; found, 389.1267.

5-Hydroxy-4-(1H-indol-3-yl)-5-phenyl-3-(p-tolyl)-1,5-dihydro-2H-pyrrol-2-one (15ab).

This compound was prepared by General Procedure C employing 4-(1H-indol-3-yl)-5-phenyl-3-(p-tolyl)-1,5-dihydro-2H-pyrrol-2-one (14ab, 91 mg, 0.25 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:1, v/v). The title compound was obtained as a yellowish solid, mp 143.1–143.8 °C (benzene), R_f 0.32 (EtOAc/hexane, 1:1, v/v). Yield 66 mg (0.17 mmol, 69%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.28 (s, 1H), 8.90 (s, 1H), 7.50–7.45 (m, 2H), 7.35 (d, J = 2.8 Hz, 1H), 7.32–7.28 (m, 2H), 7.28–7.22 (m, 3H), 7.20–7.15 (m, 1H), 7.04 (d, J = 7.9 Hz, 2H), 6.95–6.87 (m, 1H), 6.85 (s, 1H), 6.59–6.53 (m, 1H), 6.43 (d, J = 8.1 Hz, 1H), 2.25 (s, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 171.2, 150.6, 142.2, 136.4, 135.9, 130.2, 129.3 (2C), 128.3 (2C), 128.0 (2C), 127.4, 127.1, 125.9, 125.7 (2C), 124.8, 121.2, 120.1, 118.9, 111.5, 107.4, 88.1, 20.97. IR_νmax: 2996, 1772, 1685, 1656, 1555, 1506, 1422, 1370, 1242 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₅H₂₀N₂NaO₂ [M + Na]⁺, 403.1417; found, 403.1416.

3-(4-Ethylphenyl)-5-hydroxy-4-(1H-indol-3-yl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (15ac).

This compound was prepared by General Procedure C employing 3-(4-ethylphenyl)-4-(1H-indol-3-yl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (14ac, 95 mg, 0.25 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:1, v/v). The title compound was obtained as a yellowish solid, mp 201.3–204.4 °C (benzene), R_f 0.33 (EtOAc/hexane, 1:1, v/v). Yield 75 mg (0.75 mmol, 75%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.28 (s, 1H), 8.90 (s, 1H), 7.51–7.44 (m, 2H), 7.35 (d, J = 2.7 Hz, 1H), 7.34–7.29 (m, 2H), 7.28–7.21 (m, 3H), 7.20–7.15 (m, 1H), 7.10–7.04 (m, 2H), 6.93–6.87 (m, 1H), 6.85 (s, 1H), 6.57–6.48 (m, 1H), 6.38 (d, J = 8.1 Hz, 1H), 2.55 (q, J = 7.6 Hz, 2H), 1.14 (t, J = 7.6 Hz, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 171.1, 150.7, 142.8, 142.2, 135.9, 130.5, 129.4 (2C), 128.0 (2C), 127.3, 127.2, 127.1 (2C), 125.9, 125.6 (2C), 124.7, 121.2, 120.9, 118.8, 111.5, 107.3, 88.1, 28.0, 15.7. IR_νmax: 2995, 1774, 1656, 1637, 1561, 1505, 1420, 1242, 1230 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₆H₂₂N₂NaO₂ [M + Na]⁺, 417.1573; found, 417.1580.

5-Hydroxy-4-(1H-indol-3-yl)-3,5-di-p-tolyl-1,5-dihydro-2H-pyrrol-2-one (15ad).

This compound was prepared by General Procedure C employing 4-(1H-indol-3-yl)-3,5-di-p-tolyl-1,5-dihydro-2H-pyrrol-2-one (14ad, 95 mg, 0.25 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:1, v/v). The title compound was obtained as a yellowish solid, mp 149.6–150.8 °C (benzene), R_f 0.42 (EtOAc/hexane, 1:1, v/v). Yield 67 mg (0.17 mmol, 68%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.27 (s, 1H), 8.84 (s, 1H), 7.38–7.32 (m, 3H), 7.31–7.28 (m, 2H), 7.25–7.22 (m, 1H), 7.08–7.00 (m, 4H), 6.95–6.86 (m, 1H), 6.78 (s, 1H), 6.60–6.51 (m, 1H), 6.42 (d, J = 8.1 Hz, 1H), 2.25 (s, 3H), 2.20 (s, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 171.2, 150.7, 139.2, 136.4, 136.3, 135.9, 130.2, 129.3 (2C), 128.5 (2C), 128.3 (2C), 127.1, 125.7, 125.6 (2C), 124.7, 121.2, 120.9, 118.9, 111.5, 107.4, 88.1, 21.0, 20.6. IR_νmax: 2978, 1772, 1683, 1647, 1561, 1505, 1418, 1371, 1233 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₆H₂₂N₂NaO₂ [M + Na]⁺, 417.1573; found, 417.1577.

5-Hydroxy-4-(1H-indol-3-yl)-3-(4-isopropylphenyl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (15ae).

This compound was prepared by General Procedure C employing 4-(1H-indol-3-yl)-3-(4-isopropylphenyl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (14ae, 98 mg, 0.25 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:1, v/v). The title compound was obtained as a yellowish solid, mp 200.1–201.2 °C (benzene), R_f 0.36 (EtOAc/hexane, 1:1, v/v). Yield 80 mg (0.2 mmol, 78%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.28 (s, 1H), 8.89 (s, 1H), 7.51–7.44 (m, 2H), 7.37–7.34 (m, 1H), 7.33–7.30 (m, 2H), 7.29–7.21 (m, 3H), 7.20–7.15 (m, 1H), 7.14–7.07 (m, 2H), 6.92–6.87 (m, 1H), 6.86 (s, 1H), 6.54–6.45 (m, 1H), 6.31 (d, J = 8.1 Hz, 1H), 2.84 (p, J = 6.9 Hz, 1H), 1.17 (d, J = 6.9 Hz, 6H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 171.1, 150.7, 147.4, 142.3, 135.9, 130.7, 129.5 (2C), 128.0 (2C), 127.3 (2C), 125.9, 125.63 (2C), 125.59 (2C), 124.8, 121.2, 121.0, 118.7, 111.4, 107.3, 88.13 33.3, 23.9, 23.8. IR_νmax: 2984, 1774, 1667, 1655, 1521, 1505, 1420, 1387, 1237 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₇H₂₄N₂NaO₂ [M + Na]⁺, 431.1730; found, 431.1730.

5-Hydroxy-4-(1H-indol-3-yl)-5-(naphthalen-2-yl)-3-(p-tolyl)-1,5-dihydro-2H-pyrrol-2-one (15af).

This compound was prepared by General Procedure C employing 4-(1H-indol-3-yl)-5-(naphthalen-2-yl)-3-(p-tolyl)-1,5-dihydro-2H-pyrrol-2-one (14af, 104 mg, 0.25 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:1, v/v). The title compound was obtained as a yellowish solid, mp 156.2–158.4 °C (benzene), R_f 0.44 (EtOAc/hexane, 1:1, v/v). Yield 76 mg (0.18 mmol, 71%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.22 (s, 1H), 8.99 (s, 1H), 8.16 (s, 1H), 7.93–7.86 (m, 1H), 7.81–7.77 (m, 1H), 7.75 (d, J = 8.7 Hz, 1H), 7.48–7.43 (m, 2H), 7.43–7.38 (m, 2H), 7.37–7.33 (m, 2H), 7.19 (dt, J = 8.1, 1.0 Hz, 1H), 7.06 (d, J = 8.0 Hz, 2H), 7.02 (s, 1H), 6.92–6.83 (m, 1H), 6.59–6.51 (m, 1H), 6.47 (d, J = 8.1 Hz, 1H), 2.26 (s, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 171.3, 150.4, 139.6, 136.4, 135.8, 132.55, 132.3, 130.2, 129.3 (2C), 128.3 (2C), 128.1, 127.6, 127.3, 127.06, 126.12, 126.09, 126.0, 124.7, 124.4, 123.8, 121.2, 120.9, 118.9, 111.5, 107.3, 88.2, 21.0. IR_νmax: 2986, 1772, 1681, 1652, 1557, 1503, 1417, 1376, 1243 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₉H₂₂N₂NaO₂ [M + Na]⁺, 453.1573; found, 453.1571.

5-Hydroxy-4-(1H-indol-3-yl)-3-(4-methoxyphenyl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (15ag).

This compound was prepared by General Procedure C employing 4-(1H-indol-3-yl)-3-(4-methoxyphenyl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (14ag, 95 mg, 0.25 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:1, v/v). The title compound was obtained as a brown solid, mp 139.5–141.5 °C (benzene), R_f 0.36 (EtOAc/hexane, 1:1, v/v). Yield 69 mg (0.18 mmol, 70%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.27 (s, 1H), 8.89 (s, 1H), 7.47 (d, J = 7.7 Hz, 2H), 7.39–7.31 (m, 3H), 7.25 (t, J = 7.5 Hz, 3H), 7.17 (t, J = 7.3 Hz, 1H), 6.91 (t, J = 7.6 Hz, 1H), 6.81 (d, J = 3.7 Hz, 2H), 6.78 (s, 1H), 6.58 (t, J = 7.5 Hz, 1H), 6.47 (d, J = 8.1 Hz, 1H), 3.71 (s, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 171.3, 158.4, 149.8, 142.2, 135.9, 130.6 (2C), 127.9 (2C), 127.3, 126.9, 125.6 (2C), 125.5, 125.3, 124.7, 121.2, 120.9, 118.9, 113.2 (2C), 111.5, 107.4, 88.1, 55.0. IR_νmax: 2357, 1775, 1683, 1655, 1586, 1507, 1422, 1246, 1182 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₅H₂₀N₂NaO₃ [M + Na]⁺, 419.1366; found, 419.1360.

5-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-5-hydroxy-4-(1H-indol-3-yl)-3-phenyl-1,5-dihydro-2H-pyrrol-2-one (15ai).

This compound was prepared by General Procedure C employing 5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-4-(1H-indol-3-yl)-3-phenyl-1,5-dihydro-2H-pyrrol-2-one (14ai, 102 mg, 0.25 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:1, v/v). The title compound was obtained as a yellowish solid, mp 154.7–156.1 °C (benzene), R_f 0.23 (EtOAc/hexane, 1:1, v/v). Yield 70 mg (0.17 mmol, 66%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.33 (s, 1H), 8.82 (s, 1H), 7.44 (d, J = 2.8 Hz, 1H), 7.39–7.35 (m, 2H), 7.28–7.24 (m, 1H), 7.22 (dd, J = 5.1, 1.9 Hz, 3H), 6.93 (d, J = 2.2 Hz, 1H), 6.92–6.87 (m, 2H), 6.81 (s, 1H), 6.72 (d, J = 8.4 Hz, 1H), 6.58–6.49 (m, 1H), 6.34 (d, J = 8.1 Hz, 1H), 4.15 (s, 4H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 170.9, 151.0, 142.7, 142.6, 136.0, 135.3, 133.2, 129.5 (2C), 127.7 (2C), 127.5, 127.2, 125.6, 124.7, 121.2, 120.9, 118.9, 118.5, 116.6, 114.5, 111.6, 107.2, 87.8, 64.03, 63.99. IR_νmax: 2998, 2357, 1772, 1681, 1652, 1559, 1507, 1424, 1385 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₆H₂₀N₂NaO₄ [M + Na]⁺, 447.1315; found, 447.1313.

5-Hydroxy-4-(1H-indol-3-yl)-5-phenyl-3-(2,4,5-trimethoxyphenyl)-1,5-dihydro-2H-pyrrol-2-one (15ak).

This compound was prepared by General Procedure C employing 4-(1H-indol-3-yl)-5-phenyl-3-(2,4,5-trimethoxyphenyl)-1,5-dihydro-2H-pyrrol-2-one (14ak, 110 mg, 0.25 mmol). Purification was done by column chromatography (EtOAc). The title compound was obtained as a brown solid, mp 173.7–174.1 °C (benzene), R_f 0.52 (EtOAc). Yield 70 mg (0.15 mmol, 61%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.21 (s, 1H), 8.69 (s, 1H), 7.60–7.52 (m, 2H), 7.31–7.29 (m, 1H), 7.27 (d, J = 1.5 Hz, 1H), 7.26–7.22 (m, 1H), 7.21 (d, J = 0.9 Hz, 1H), 7.20–7.15 (m, 1H), 6.95–6.86 (m, 1H), 6.81 (s, 1H), 6.70 (d, J = 13.9 Hz, 2H), 6.64 (d, J = 8.1 Hz, 1H), 6.61–6.56 (m, 1H), 3.79 (s, 3H), 3.50 (s, 3H), 3.46 (s, 3H).; ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 171.0, 152.7, 151.6, 149.6, 142.9, 142.3, 135.8, 127.9 (2C), 127.23, 127.19, 125.6 (2C), 125.4, 124.7, 121.1, 120.8, 118.9, 115.8, 114.6, 111.3, 108.3, 99.0, 88.4, 56.5, 56.3, 55.8. IR_νmax: 2977, 1770, 1683, 1632, 1557, 1507, 1414, 1238, 1214 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₇H₂₄N₂NaO₅ [M + Na]⁺, 479.1577; found, 479.1574.

3-(2-Fluorophenyl)-5-hydroxy-4-(1H-indol-3-yl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (15al).

This compound was prepared by General Procedure C employing 3-(2-fluorophenyl)-4-(1H-indol-3-yl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (14al, 92 mg, 0.25 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:1, v/v). The title compound was obtained as a yellow solid, mp 138.9–140.6 °C (benzene), R_f 0.23 (EtOAc/hexane, 1:1, v/v). Yield 51 mg (0.13 mmol, 53%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.37 (d, J = 2.9 Hz, 1H), 8.94 (s, 1H), 7.61–7.50 (m, 2H), 7.39 (d, J = 2.8 Hz, 1H), 7.38–7.33 (m, 2H), 7.32–7.27 (m, 2H), 7.26–7.23 (m, 1H), 7.23–7.19 (m, 1H), 7.18–7.16 (m, 1H), 7.15–7.10 (m, 1H), 7.00 (s, 1H), 6.95–6.87 (m, 1H), 6.59–6.50 (m, 1H), 6.43 (d, J = 8.1 Hz, 1H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 170.2, 160.2 (d, J = 247.6 Hz), 153.7, 142.4, 135.9, 132.1 (d, J = 3.7 Hz), 129.7 (d, J = 8.1 Hz), 128.1 (2C), 127.9, 127.5, 125.5 (2C), 125.0, 124.0 (d, J = 3.7 Hz), 121.8 (d, J = 15.8 Hz), 121.4, 121.3, 119.9, 119.2, 115.5 (d, J = 21.6 Hz), 111.7, 107.4, 88.6; ¹⁹F NMR (376 MHz, DMSO-d₆): δ −111.09. IR_νmax: 2834, 1770, 1674, 1655, 1556, 1505, 1434, 1376, 1241 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₄H₁₇FN₂NaO₂ [M + Na]⁺, 407.1166; found, 407.1171.

3-(4-Chlorophenyl)-5-hydroxy-4-(1H-indol-3-yl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (15am).

This compound was prepared by General Procedure C employing 3-(4-chlorophenyl)-4-(1H-indol-3-yl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (14am, 96 mg, 0.25 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:1, v/v). The title compound was obtained as a yellowish solid, mp 141.6–142.4 °C (benzene), R_f 0.42 (EtOAc/hexane, 1:1, v/v). Yield 60 mg (0.15 mmol, 58%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.37 (s, 1H), 9.00 (s, 1H), 7.51–7.44 (m, 2H), 7.42 (d, J = 1.9 Hz, 1H), 7.40 (q, J = 2.4 Hz, 2H), 7.30 (d, J = 2.1 Hz, 1H), 7.29–7.27 (m, 2H), 7.27–7.23 (m, 2H), 7.21–7.15 (m, 1H), 6.98–6.89 (m, 2H), 6.66–6.57 (m, 1H), 6.40 (d, J = 8.1 Hz, 1H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 170.7, 151.7, 141.9, 136.0, 132.0, 131.8, 131.1 (2C), 128.0 (2C), 127.8 (2C), 127.5, 127.4, 125.6 (2C), 124.4 (2C), 121.4, 120.6, 119.1, 111.8, 106.9, 88.2. IR_νmax: 2996, 1772, 1683, 1648, 1634, 1557, 1420, 1374, 1090 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₄H₁₇ClN₂NaO₂ [M + Na]⁺, 423.0871; found, 423.0866.

3-(4-Bromophenyl)-5-hydroxy-4-(1H-indol-3-yl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (15an).

This compound was prepared by General Procedure C employing 3-(4-bromophenyl)-4-(1H-indol-3-yl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (14an, 107 mg, 0.25 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:1, v/v). The title compound was obtained as a yellowish solid, mp 144.2–144.8 °C (benzene), R_f 0.42 (EtOAc/hexane, 1:1, v/v). Yield 62 mg (0.14 mmol, 56%). ¹H NMR (400 MHz, DMSO-d₆): δ 11.37 (s, 1H), 9.00 (s, 1H), 7.50–7.46 (m, 2H), 7.45–7.41 (m, 2H), 7.40 (d, J = 2.8 Hz, 1H), 7.38–7.33 (m, 2H), 7.29–7.23 (m, 3H), 7.21–7.13 (m, 1H), 6.96–6.91 (m, 2H), 6.66–6.58 (m, 1H), 6.41 (d, J = 8.1 Hz, 1H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 170.6, 151.7, 141.9, 136.0, 132.3, 131.4 (2C), 130.7 (2C), 128.0 (2C), 127.43, 127.37, 125.6 (2C), 124.5, 124.4, 121.4, 120.6, 120.5, 119.1, 111.7, 106.9, 88.2. IR_νmax: 2998, 1772, 1683, 1652, 1559, 1505, 1418, 1242, 1057 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₄H₁₇BrN₂NaO₂ [M + Na]⁺, 467.0366; found, 467.0362.

5-Hydroxy-4-(2-methyl-1H-indol-3-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (15ba).

This compound was prepared by General Procedure C employing 4-(2-methyl-1H-indol-3-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (14ba, 91 mg, 0.25 mmol). Purification was done by column chromatography (EtOAc/hexane, 2:1, v/v). The title compound was obtained as a yellowish solid, mp 146.8–148.5 °C (benzene), R_f 0.36 (EtOAc/hexane, 2:1, v/v). Yield 66 mg (0.17 mmol, 69%). ¹H NMR (400 MHz, DMSO-d₆): δ 10.84 (s, 1H), 9.11 (s, 1H), 7.32–7.25 (m, 5H), 7.21–7.16 (m, 4H), 7.16 (s, 2H), 7.12 (d, J = 7.9 Hz, 1H), 6.91 (t, J = 7.1 Hz, 1H), 6.76 (s, 2H), 1.52 (s, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 171.0, 154.1, 140.9, 135.3, 134.1, 132.5, 130.8, 128.6 (2C), 128.4, 128.0, 127.73 (2C), 127.70 (2C), 127.4, 127.3, 125.9 (2C), 120.1, 118.7, 110.3, 104.2, 89.0, 11.9. IR_νmax: 2984, 1770, 1747, 1651, 1633, 1557, 1505, 1420, 1238 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₅H₂₀N₂NaO₂ [M + Na]⁺, 403.1417; found, 403.1425.

General Procedure for the Preparation of 5-Hydroxy-3,5-diaryl-1,5-dihydro-2H-pyrrol-2-ones (D)

This method is an adaptation of a reported procedure.³¹ In a 25 mL vial equipped with a magnetic stirring bar, KOH (4 equiv, 0.672 g, 12 mmol) was dissolved in H₂O (2 mL), followed by the addition of 4-oxo-2,4-diarylbutanenitrile³³ (1 equiv, 3 mmol) and DMSO (6 mL). The reaction mixture was allowed to stir at rt for approximately 1 h. After the consumption of all the starting compounds, the reaction mixture was diluted with water (50 mL), extracted with EtOAc (4 × 50 mL), washed with H₂O (2 × 50 mL), and purified by column chromatography (EtOAc/hexane 1:3–1:1).

5-Hydroxy-3-(4-isopropylphenyl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (11e).

This compound was prepared by General Procedure D employing 2-(4-isopropylphenyl)-4-oxo-4-phenylbutanenitrile³³ (831 mg, 3.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:2, v/v). The title compound was obtained as a yellow solid, mp 195.1–198.5 °C (EtOAc), R_f 0.56 (EtOAc/hexane, 1:2, v/v). Yield 519 mg (1.77 mmol, 59%). ¹H NMR (400 MHz, DMSO-d₆): δ 9.06 (s, 1H), 7.89–7.84 (m, 2H), 7.55–7.50 (m, 2H), 7.40–7.34 (m, 2H), 7.33–7.29 (m, 2H), 7.28–7.22 (m, 2H), 6.60 (s, 1H), 2.88 (hept, J = 6.9 Hz, 1H), 1.20 (d, 6H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 171.0, 148.9, 144.9, 141.0, 131.9, 128.8, 128.2 (2C), 127.82, 127.3 (2C), 126.2 (2C), 125.7 (2C), 86.1, 33.3, 23.7 (2C). IR_νmax: 3247, 2952, 1675, 1629, 1509, 1419, 1219 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₁₉H₁₉NNaO₂ [M + Na]⁺, 316.1308; found, 316.1316.

5-Hydroxy-5-(naphthalen-2-yl)-3-(p-tolyl)-1,5-dihydro-2H-pyrrol-2-one (11f).

This compound was prepared by General Procedure D employing 4-(naphthalen-2-yl)-4-oxo-2-(p-tolyl)butanenitrile³³ (897 mg, 3.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:2, v/v). The title compound was obtained as a colorless solid, mp 216.3–223.1 °C (EtOAc), R_f 0.49 (EtOAc/hexane, 1:2, v/v). Yield 720 mg (2.13 mmol, 71%). ¹H NMR (400 MHz, DMSO-d₆): δ 9.21 (s, 1H), 8.11 (s, 1H), 7.98–7.93 (m, 1H), 7.93–7.87 (m, 4H), 7.58–7.54 (m, 1H), 7.54–7.49 (m, 2H), 7.42 (s, 1H), 7.21 (d, J = 7.9 Hz, 2H), 6.77 (s, 1H), 2.31 (s, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 171.1, 144.7, 138.5, 138.1, 132.7, 132.6, 132.0, 129.0 (2C), 128.4, 128.2, 127.9, 127.5, 127.2 (2C), 126.3, 126.3, 124.3, 124.2, 86.2, 21.0. IR_νmax: 3255, 1754, 1651, 1561, 1511, 1418, 1271 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₂₁H₁₇NNaO₂ [M + Na]⁺, 338.1151; found, 338.1159.

5-Hydroxy-5-phenyl-3-(2,4,5-trimethoxyphenyl)-1,5-dihydro-2H-pyrrol-2-one (11k).

This compound was prepared by General Procedure D employing 4-oxo-4-phenyl-2-(2,4,5-trimethoxyphenyl)butanenitrile³³ (975 mg, 3.00 mmol). Purification was done by column chromatography (EtOAc/hexane, 1:1, v/v). The title compound was obtained as a yellow solid, mp 183.5–185.2 °C (EtOAc), R_f 0.3 (EtOAc/hexane, 1:1, v/v). Yield 460 mg (1.35 mmol, 45%). ¹H NMR (400 MHz, DMSO-d₆): δ 9.05 (s, 1H), 8.15 (s, 1H), 7.54–7.45 (m, 2H), 7.39–7.33 (m, 2H), 7.32–7.27 (m, 2H), 6.72 (s, 1H), 6.52 (s, 1H), 3.82 (s, 3H), 3.80 (s, 3H), 3.70 (s, 3H); ¹³C{¹H} NMR (101 MHz, DMSO-d₆): δ 171.9, 153.4, 149.7, 146.7, 141.8, 141.4, 128.2 (2C), 127.7, 126.8, 125.7 (2C), 113.7, 110.9, 97.7, 86.0, 56.2, 56.0, 55.7. IR_νmax: 3235, 3013, 1768, 1668, 1496, 1377, 1277 cm⁻¹; HRMS (ESI TOF) m/z: calcd for C₁₉H₁₉NNaO₅ [M + Na]⁺, 364.1155; found, 364.1163.

CELL CULTURE CONDITIONS

The triple-negative breast cancer cell line MDA-MB-231 was purchased from the American Type Culture Collection. The cells were incubated in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% fetal bovine serum, 1% antibiotic containing penicillin, streptomycin, and amphotericin B solution (Corning), and 1% amino acid supplement containing l-alanyl-l-glutamine (Glutagro, Corning). To simulate the normal conditions (normoxia), 5% carbon dioxide, 21% oxygen, and 74% nitrogen gas composition were utilized in a humidified incubator at 37 °C. To simulate the intratumoral hypoxic niches (hypoxia), 5% carbon dioxide, 0.2% oxygen, and 94.8% nitrogen gas composition were utilized in a humidified glovebox at 37 °C (Coy Laboratories). A2780 and OVCAR-5 ovarian cancer cell lines were obtained from ECACC and ATCC, respectively, and cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum (FBS) and 5% penicillin–streptomycin. Cells were cultured in a humidified atmosphere at 37 °C with 5% CO₂.

CELL VIABILITY STUDIES

To determine the toxicity of the compounds to triple-negative breast cancer cells in normoxic and hypoxic conditions, 5000 MDA-MB-231 cells were seeded in a 96-well plate and incubated until 90% confluency. Subsequently, the cells were treated with the compounds in concentrations of 10 μM dissolved in DMSO for 72 h. Compounds were tested in both normoxic and hypoxic conditions using the Alamar blue assay with five replicates and an equal amount of DMSO added as control. Ovarian cancer cell viability in response to compound treatment was assessed by MTT assay. A2780 and OVCAR-5 cells were seeded at 2500 cells/mL in 96-well clear, flat-bottom, black-walled plates. After 24 h, the cells were treated with the test compounds at varying concentrations prepared from 1 mM stock solutions in DMSO. A2780 cells were treated with 5, 10, and 25 μM, while OVCAR-5 cells were treated with 5, 10, 25, and 50 μM for 72 h. The compounds were tested under normoxic conditions. DMSO amount corresponding to the 10 μM concentration treatment group was used as the vehicle control, while untreated cells were used as controls.

Supplementary Material

Supporting Information

NIHMS2141551-supplement-Supporting_Information.pdf^{(9.9MB, pdf)}

ASSOCIATED CONTENT

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.joc.5c02314.

Copies of ¹H, ¹³C, and ¹⁹F NMR spectra for all new compounds as well as X-ray data for compound 14ac (PDF)

ACKNOWLEDGMENTS

The synthetic studies were supported by a grant from the Russian Science Foundation (No. 25–73-20003; https://rscf.ru/en/project/25-73-20003/). S.M. acknowledges the NIH Award 2R01 GM 114080 for partial support of this study. T.H. acknowledges support from NIH P01 CA084203 and R01 CA260340. M.A.S. acknowledges support from NIH U54 CA156734.

Footnotes

The authors declare no competing financial interest.

Accession Codes

Deposition Number 2472264 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via the joint Cambridge Crystallographic Data Centre (CCDC) and Fachinformationszentrum Karlsruhe Access Structures service.

Contributor Information

Dmitrii A. Aksenov, Department of Chemistry, North Caucasus Federal University, Stavropol 355009, Russian Federation.

Connor Edvall, Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota 58105, United States.

Shivendran Vytheswaran, Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, United States.

Puppala Sathish, Department of Chemistry and Biochemistry, Texas State University, San Marcos, Texas 78666, United States.

Alesia S. Akulova, Department of Chemistry, North Caucasus Federal University, Stavropol 355009, Russian Federation

Nicolai A. Aksenov, Department of Chemistry, North Caucasus Federal University, Stavropol 355009, Russian Federation

Tatyana S. Galushko, Department of Chemistry, North Caucasus Federal University, Stavropol 355009, Russian Federation

Tayyaba Hasan, Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, United States; Division of Health Sciences and Technology, Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts 02115, United States.

Alexander V. Aksenov, Department of Chemistry, North Caucasus Federal University, Stavropol 355009, Russian Federation

Sanku Mallik, Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota 58105, United States.

Mohammad A. Saad, Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, United States

Alexander Kornienko, Department of Chemistry and Biochemistry, Texas State University, San Marcos, Texas 78666, United States.

Data Availability Statement

The data underlying this study are available in the published article and its Supporting Information.

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Associated Data

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

Supplementary Materials

Supporting Information

NIHMS2141551-supplement-Supporting_Information.pdf^{(9.9MB, pdf)}

Data Availability Statement

The data underlying this study are available in the published article and its Supporting Information.

[R1] (1).Evans BE; Rittle KE; Bock MG; Dipardo RM; Freidinger RM; Whitter WL; Lundell GF; Veber DF; Anderson PS; Chang RSL; Lotti VJ; Cerino DJ; Chen TB; Kling PJ; Kunkel KA; Springer JP; Hirshfield J Methods for drug discovery: Development of potent, selective, orally effective cholecystokinin antagonist. J. Med. Chem. 1988, 31, 2235–2246. [DOI] [PubMed] [Google Scholar]

[R2] (2).Skoreński M; Sienczyk M The fellowship of privileged scaffolds – one structure to inhibit them all. Pharmaceuticals 2021, 14, No. 1164. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R3] (3).Peifer C; Selig R; Kinkel K; Ott D; Totzke F; Schachtele C; Heidenreich R; Rocken M; Schollmeyer D; Laufer S Design, synthesis, and biological evaluation of novel 3-aryl-4-(1H-indole-3yl)-1,5-dihydro-2H-pyrrole-2-ones as vascular endothelial growth factor receptor (VEGF-R) inhibitors. J. Med. Chem. 2008, 51, 3814–3824. [DOI] [PubMed] [Google Scholar]

[R4] (4).Kirby LA; Schott JT; Brenda LN; Mendez DC; Caseley PS; Peterson SC; Routledge TJ; Patel NV Glycogen synthase kinase 3 (GSK3) inhibitor, SB-216763, promotes pluripotency in mouse embryonic stem cells. PLoS One 2012, 7, No. e39329. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R5] (5).Levy DE; Wang D-X; Lu Q; Chen Z; Perumattam J; Xu Y. -j.; Liclican A; Higaki J; Dong H; Laney M; Mavunkel B; Dugar S Aryl-indolyl maleimides as inhibitors of CaMKIId. Part 1: SAR of the aryl region. Bioorg. Med. Chem. Lett. 2008, 18, 2390–2394. [DOI] [PubMed] [Google Scholar]

[R6] (6).Surmiak E; Twarda-Clapa A; Zak KM; Musielak B; Tomala MD; Kubica K; Grudnik P; Madej M; Jablonski M; Potempa J; Kalinowska-Tluscik J; Domling A; Dubin G; Holak TA A unique mdm2-binding mode of the 3-pyrrolin-2-one and 2-furanone-based antagonists of the p53-mdm2 interaction. ACS Chem. Biol. 2016, 11, 3310–3318. [DOI] [PubMed] [Google Scholar]

[R7] (7).Mowery P; Mejia FB; Franceschi CL; Kean MH; Kwansare DO; Lafferty MM; Neerukonda ND; Rolph CE; Truax NJ; Pelkey ET Synthesis and evaluation of the anti-proliferative activity of diaryl-3-pyrrolin-2-ones and fused analogs. Bioorg. Med. Chem. Lett. 2017, 27, 191–195. [DOI] [PubMed] [Google Scholar]

[R8] (8).An Y-L; Yang Z-H; Zhang H-H; Zhao S-Y Palladium-catalyzed tandem regioselective oxidative coupling from indoles and maleimides: one-pot synthesis of indolopyrrolocarbazoles and related indolylmaleimides. Org. Lett. 2016, 18, 152–155. [DOI] [PubMed] [Google Scholar]

[R9] (9).Abaev VT; Aksenov NA; Aksenov DA; Aleksandrova EV; Akulova AS; Kurenkov IA; Leontiev AV; Aksenov AV One-pot synthesis of polynuclear indole derivatives by Friedel-Crafts alkylation of g-hydroxybutyrolactams. Molecules 2023, 28, No. 3162. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R10] (10).Zhu P-L; Zhang Z; Tang X-Y; Marek I; Shi M Gold and silver-catalyzed cyclizations of indolylcyclopropenes for the divergent synthesis of azepinoindoles and spiroindoline piperidines. ChemCatChem. 2015, 7, 595–600. [Google Scholar]

[R11] (11).Zhou Y; Xia Z-L; Gu Q; You S-L Chiral phosphoric acid catalyzed intramolecular dearomative Michael addition of indoles to enones. Org. Lett. 2017, 19, 762–765. [DOI] [PubMed] [Google Scholar]

[R12] (12).Jana GK; Sinha S Total synthesis of ibogaine, epiibogane and their analogues. Tetrahedron 2012, 68, 7155–7165. [Google Scholar]

[R13] (13).Bajtos B; Pagenkopf BL Total synthesis of (±)-quebrachamine via [3 + 2] cycloaddition and efficient chloroacetamide photocyclization. Eur. J. Org. Chem. 2009, 2009, 1072–1077. [Google Scholar]

[R14] (14).Shiraki R; Sumino A; Tadano K. -i.; Ogawa S Total synthesis of natural PI-091, a new platelet aggregation inhibitor of microbial origin. J. Org. Chem. 1996, 61, 2845–2852. [DOI] [PubMed] [Google Scholar]

[R15] (15).Kuramochi K; Matsui R; Matsubara Y; Nakai J; Sunoki T; Arai S; Nagata S; Nagahara Y; Yoshiyuki; Mizushina Y; Ikekita M; Kobayashi S. Apoptosis-inducing effect of epolactaene derivatives on BALL-1 cells. Bioorg. Med. Chem. 2006, 14, 2151–2161. [DOI] [PubMed] [Google Scholar]

[R16] (16).Lei Y-E; Wang Q; Yaermaimaiti S; Ma Z-H; Li M-M; Lu Y; Chen D-F; Wang Q Fulvanines J-K, two rare lactam pyrrole alkaloids from Hemerocallis fulva. Chem. Biodiversity 2024, 21, No. e202301672. [DOI] [PubMed] [Google Scholar]

[R17] (17).Wang X; Zhao L; Liu C; Qi J; Zhao P; Liu Z; Li C; Hu Y; Yin X; Liu X; Liao Z; Zhang L; Xia X New tetramic acids comprising of decalin and pyridines from Chaetomium olivaceum SD-80A with antimicrobial activity. Front. Microbiol. 2020, 10, No. 2958. [DOI] [PMC free article] [PubMed] [Google Scholar]

[R18] (18).Chebolu R; Bahuguna A; Sharma R; Mishra VK; Ravikumar PC An unusual chemoselective oxidation strategy by an unprecedented exploration of an electrophilic center of DMSO: a new facet to classical DMSO oxidation. Chem. Commun. 2015, 51 (84), 15438–15441. [DOI] [PubMed] [Google Scholar]

[R19] (19).Ang WJ; Lam Y Allylic and benzylic sp3 C–H oxidation in water. Org. Biomol. Chem. 2015, 13 (4), 1048–1052. [DOI] [PubMed] [Google Scholar]

[R20] (20).Pak VN; Kasaritskaya OV; Alekseeva NV; Kun Sh. R.; Badger S. The oxidation of phenol on the surface of silica gel. Russ. J. Phys. Chem. A 2004, 78 (11), 1734–1738. [Google Scholar]

[R21] (21).Nakada M; Nakamura A Allylic oxidations in natural product synthesis. Synthesis 2013, 45 (11), 1421–1451. [Google Scholar]

[R22] (22).Młochowski J; Wójtowicz-Młochowska H Developments in synthetic application of Selenium(IV) oxide and organoselenium compounds as oxygen donors and Oxygen-Transfer agents. Molecules 2015, 20 (6), 10205–10243. [DOI] [PMC free article] [PubMed] [Google Scholar]

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PERMALINK

Rearrangement of 5-Indolyl-3-pyrrolin-2-ones into Privileged 4-Indolyl-3-pyrrolin-2-ones Leads to Identification of Antiproliferative Compounds Active under Hypoxia

Dmitrii A Aksenov

Connor Edvall

Shivendran Vytheswaran

Puppala Sathish

Alesia S Akulova

Nicolai A Aksenov

Tatyana S Galushko

Tayyaba Hasan

Alexander V Aksenov

Sanku Mallik

Mohammad A Saad

Alexander Kornienko

Abstract

Graphical Abstract

INTRODUCTION

Figure 1.

Figure 2.

RESULTS AND DISCUSSION

Figure 3.

Table 1.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

Table 2.

Figure 8.

Figure 9.

Table 3.

CONCLUSIONS

EXPERIMENTAL SECTION

General Information

General Procedure for the Preparation of 4-(1H-Indol-3-yl)-3,5-diaryl-1,5-dihydro-2H-pyrrol-2-ones (A)

4-(1H-Indol-3-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (14aa).

4-(1H-Indol-3-yl)-5-phenyl-3-(p-tolyl)-1,5-dihydro-2H-pyrrol-2-one (14ab).

3-(4-Ethylphenyl)-4-(1H-indol-3-yl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (14ac).

4-(1H-Indol-3-yl)-3,5-di-p-tolyl-1,5-dihydro-2H-pyrrol-2-one (14ad).

4-(1H-Indol-3-yl)-3-(4-isopropylphenyl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (14ae).

4-(1H-Indol-3-yl)-5-(naphthalen-2-yl)-3-(p-tolyl)-1,5-dihydro-2H-pyrrol-2-one (14af).

4-(1H-Indol-3-yl)-3-(4-methoxyphenyl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (14ag).

4-(1H-Indol-3-yl)-3,5-bis(4-methoxyphenyl)-1,5-dihydro-2H-pyrrol-2-one (14ah).

5-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-4-(1H-indol-3-yl)-3-phenyl-1,5-dihydro-2H-pyrrol-2-one (14ai).

4-(1H-Indol-3-yl)-5-(4-methoxyphenyl)-3-phenyl-1,5-dihydro-2H-pyrrol-2-one (14aj).

4-(1H-Indol-3-yl)-5-phenyl-3-(2,4,5-trimethoxyphenyl)-1,5-dihydro-2H-pyrrol-2-one (14ak).

3-(2-Fluorophenyl)-4-(1H-indol-3-yl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (14al).

3-(4-Chlorophenyl)-4-(1H-indol-3-yl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (14am).

3-(4-Bromophenyl)-4-(1H-indol-3-yl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (14an).

4-(2-Methyl-1H-indol-3-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (14ba).

4-(2-Hydroxynaphthalen-1-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (14ca).

4-(2,4-Dihydroxyphenyl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (14da).

4-(5-Chloro-2-methyl-1H-indol-3-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (14ea).

4-(5-Bromo-2-methyl-1H-indol-3-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (14fa).

4-(2-Methyl-5-nitro-1H-indol-3-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (14ga).

General Procedure for the Preparation of 5-(1H-Indol-3-yl)-3,5-diaryl-1,5-dihydro-2H-pyrrol-2-ones (B)

5-(1H-Indol-3-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (12aa).

5-(1H-Indol-3-yl)-5-phenyl-3-(p-tolyl)-1,5-dihydro-2H-pyrrol-2-one (12ab).

3-(4-Ethylphenyl)-5-(1H-indol-3-yl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (12ac).

5-(1H-Indol-3-yl)-3,5-di-p-tolyl-1,5-dihydro-2H-pyrrol-2-one (12ad).

5-(1H-Indol-3-yl)-3-(4-isopropylphenyl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (12ae).

5-(1H-Indol-3-yl)-5-(naphthalen-2-yl)-3-(p-tolyl)-1,5-dihydro-2H-pyrrol-2-one (12af).

5-(1H-Indol-3-yl)-3-(4-methoxyphenyl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (12ag).

5-(1H-Indol-3-yl)-3,5-bis(4-methoxyphenyl)-1,5-dihydro-2H-pyrrol-2-one (12ah).

5-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-5-(1H-indol-3-yl)-3-phenyl-1,5-dihydro-2H-pyrrol-2-one (12ai).

5-(1H-Indol-3-yl)-5-(4-methoxyphenyl)-3-phenyl-1,5-dihydro-2H-pyrrol-2-one (12aj).

5-(1H-Indol-3-yl)-5-phenyl-3-(2,4,5-trimethoxyphenyl)-1,5-dihydro-2H-pyrrol-2-one (12ak).

3-(2-Fluorophenyl)-5-(1H-indol-3-yl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (12al).

3-(4-Chlorophenyl)-5-(1H-indol-3-yl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (12am).

3-(4-Bromophenyl)-5-(1H-indol-3-yl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (12an).

5-(2-Methyl-1H-indol-3-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (12ba).

5-(2-Hydroxynaphthalen-1-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (12ca).

5-(2,4-Dihydroxyphenyl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (12da).

5-(5-Chloro-2-methyl-1H-indol-3-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (12ea).

5-(5-Bromo-2-methyl-1H-indol-3-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (12fa).

5-(2-Methyl-5-nitro-1H-indol-3-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (12ga).

General Procedure for the Preparation of 5-Hydroxy-4-(1H-indol-3-yl)-3,5-diaryl-1,5-dihydro-2H-pyrrol-2-ones (C)

5-Hydroxy-4-(1H-indol-3-yl)-3,5-diphenyl-1,5-dihydro-2H-pyrrol-2-one (15aa).

5-Hydroxy-4-(1H-indol-3-yl)-5-phenyl-3-(p-tolyl)-1,5-dihydro-2H-pyrrol-2-one (15ab).

3-(4-Ethylphenyl)-5-hydroxy-4-(1H-indol-3-yl)-5-phenyl-1,5-dihydro-2H-pyrrol-2-one (15ac).

5-Hydroxy-4-(1H-indol-3-yl)-3,5-di-p-tolyl-1,5-dihydro-2H-pyrrol-2-one (15ad).