Ruthenium(II)-Catalyzed Redox-Free [3 + 2] Cycloaddition of N

Mar 2, 2018 - A ruthenium(II)-catalyzed redox-free cycloaddition of N-sulfonyl aromatic aldimines with maleimides providing 1-aminoindanes in good yie...
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Cite This: J. Org. Chem. 2018, 83, 3746−3755

Ruthenium(II)-Catalyzed Redox-Free [3 + 2] Cycloaddition of N‑Sulfonyl Aromatic Aldimines with Maleimides Masilamani Tamizmani, Balu Ramesh, and Masilamani Jeganmohan* Department of Chemistry, Indian Institute of Technology Madras, Chennai 600036, Tamil Nadu, India S Supporting Information *

ABSTRACT: A ruthenium(II)-catalyzed redox-free cycloaddition of N-sulfonyl aromatic aldimines with maleimides providing 1-aminoindanes in good yields is described. Usually, maleimides reacted with substituted aromatics, affording the Michael-type ortho alkylated aromatics or 1,1-type cyclized spirosuccinimides. In the present reaction, maleimides provided 1,2-type cycloaddition products. The proposed mechanism was strongly supported by the DFT calculations and isolation of a ruthenacycle intermediate.

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INTRODUCTION The synthesis of carbocyclic and heterocyclic molecules by the transition-metal-catalyzed, chelation-assisted oxidative cyclization of substituted aromatics or heteroaromatics with carbon-carbon π-components is a powerful method in organic synthesis.1−3 By employing this method, several carbocyclic and heterocyclic molecules are synthesized efficiently in a highly atom-economical and environmentally friendly manner from the easily available and affordable starting materials. Carbon-carbon π-components such as alkynes and allenes are frequently used for this type of transformation.3 Generally, substituted aromatics or heteroaromatics reacted with alkenes, providing ortho alkenylated or alkylated aromatics and heteroaromatics.1−3 In a few cases, the heteroatom such as oxygen or nitrogen of the directing group undergoes intramolecular nucleophilic addition with an alkene moiety of ortho alkenylated aromatics, giving heterocyclic molecules.2d,3 Thus, alkenes are less explored as an efficient π-component for the cyclization reaction. In this type of alkenylation reaction also, mostly activated alkenes, styrenes, and unactivated alkenes are employed.2d,4 However, cyclic alkenes and internal alkenes are less explored.4 Recently, maleimides are efficiently used as an alkene source for this type of reaction (Scheme 1).5 Mostly, maleimides reacted with substituted aromatics, providing the Michael-type ortho alkylated aromatics.5 Miura’s group and we found an unusual 1,1-type oxidative cyclization of benzamides with maleimides assisted by an 8-aminoquinoline ligand, giving isoindolone spirosuccinimides in the presence of the first row copper or cobalt metal (Scheme 1).6 © 2018 American Chemical Society

Scheme 1. General Reaction of Maleimides

Our continuous interest on a less expensive ruthenium-catalyzed C−H bond functionalization reaction prompted us to explore the possibility of cycloaddition of substituted aromatics with maleimides.7−9 Herein, we report a different type of 1,2-type cycloaddition of substituted aromatics with maleimides in the presence of a ruthenium(II) catalyst in a redox-free version. Generally, maleimides reacted with aromatics, providing Michael-type ortho alkylated aromatics or 1,1-type cyclized products.5,6 In the present reaction, maleimide undergoes 1,2-type cycloaddition with aromatic aldimines, providing 1-aminoindanes in good to excellent Received: January 12, 2018 Published: March 2, 2018 3746

DOI: 10.1021/acs.joc.8b00102 J. Org. Chem. 2018, 83, 3746−3755

Article

The Journal of Organic Chemistry yields. 1-Aminoindanes found widespread applications in biological and material science.7e The sulfonylimine (NSO2R) directing group plays a key role for the success of the cycloaddition reaction.7 In the present cycloaddition, the ruthenium(II) oxidation state is involved in the whole catalytic cycle. It is a redox-free reaction, and thus oxidant is not needed to regenerate the catalyst. The cycloaddition reaction was compatible with various benzaldimines and maleimides. A possible reaction mechanism is proposed and strongly supported by the isolation of a key fivemembered ruthenacycle intermediate and the DFT calculations.

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RESULTS AND DISCUSSION When N-sulfonyl benzaldimine (1a) was treated with N-ethyl maleimide (2a) in the presence of [(p-cymene)Ru(CH3CN)3][SbF6]2 (5 mol %) and Cu(OAc)2·H2O (25 mol %) in ClCH2CH2Cl (DCE) at 90 °C for 16 h, 1-aminoindane derivative 3aa was observed in 92% isolated yield in a highly diastereoselective manner (Scheme 2, Table 1). In the reaction,

Figure 1. ORTEP diagram of 3ia (50% probability ellipsoids) (CCDC. 1583871).

Scheme 2. General Reaction of Maleimides

shows a similar reactivity in the reaction and it can be handled easily without being under an inert atmosphere. The cycloaddition reaction was examined with various solvents such as toluene, DMF, THF, MeOH, and CH3CN apart from ClCH2CH2Cl. THF and toluene gave product 3aa in 45% and 40% yields, respectively. The remaining solvents were inactive toward this reaction. The reaction was examined with acetate and carbonate sources such as LiOAc, NaOAc, KOAc, and Li2CO3 apart from Cu(OAc)2·H2O (25 mol %). Li2CO3 was equally reactive as like Cu(OAc)2·H2O, giving product 3aa in 90% yield. LiOAc was partially effective, giving product 3aa in 65% yield. NaOAc and KOAc were less effective for the reaction. The catalytic reaction was examined with AcOH, pivalic acid, Adm-1-COOH, and mesitylenic acid instead of Cu(OAc)2·H2O (25 mol %). However, no product 3aa was observed. The reaction was also examined with anhydrous Cu(OAc)2. However, in the reaction, product 3aa was observed only in 67% yield. It seems an acetate or carbonate source is crucial for the reaction. The reaction was examined with 0.5 equiv and 1.0 equiv of Cu(OAc)2·H2O. In the reaction, product 3aa was observed in 82% and 70% yields along with hydrolysis of 1a. The optimization study clearly revealed that the [(p-cymene)Ru(CH3CN)3][SbF6]2 (5 mol %) and Cu(OAc)2·H2O (25 mol %) in ClCH2CH2Cl (DCE) at 90 °C for 16 h are the best conditions for the reaction. The scope of cycloaddition reaction was examined with various sensitive functional groups such as SMe, Br, Cl, and F substituted N-sulfonyl aromatic aldimines (Table 2). The reaction of electron-donating OMe, Me, iso-Pr, and SMe substituents at the para position of benzaldimines 1b−e with 2a under the optimized reaction conditions provided the expected 1-aminoindane derivatives 3ba−ea in 80, 75, 90, and 55% yields, respectively (entries 1−4). Halogen Br, Cl, and F substituents at the para position of benzaldimines 1f−h also efficiently participated in the reaction, giving products 3fa−ha in 56, 61, and 60% yields, respectively (entries 5−7). Ortho methyl and fluoro substituted benzaldimines 1i−j yielded the expected products 3ia and 3ja in 90% and 56% yields, respectively (entries 8 and 9). N-Sulfonyl 1-naphthylaldimine (1k) reacted efficiently with 2a, giving product 3ka in 80% yield (entry 10). A single diastereomer was observed for all compounds, and the diastereoselectivity was further confirmed by a single-crystal X-ray analysis (Figure 1). The cycloaddition reaction was examined with unsymmetrical N-sulfonyl aromatic aldimines 1l−n (Scheme 3).

Table 1. Optimization Study of Cycloaddition Reactiona entry

solvent

additive

yield (%)b

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

DCE DCE DCE DCE DCE DCE DMF THF MeOH CH3CN toluene DCE DCE DCE DCE

Li2CO3 NaOAc KOAc LiOAc Cu(OAc)2 Cu(OAc)2·H2O Cu(OAc)2·H2O Cu(OAc)2·H2O Cu(OAc)2·H2O Cu(OAc)2·H2O Cu(OAc)2·H2O CH3COOH pivalic acid Adm-1-COOH mestylinic acid

90 trace trace 65 67 92 trace 45 NR trace 40 NR NR NR NR

a

All reactions were carried out using 1a (0.33 mmol), 2a (0.42 mmol), and additive (25 mol %) in solvent (3.0 mL) under N2 at 90 °C for 16 h. bIsolated yield.

only a single diastereoisomer was observed selectively. In the product 3aa, the H of benzylic carbon containing NHTs and the H of maleimide derived proton are trans to each other (see Figure 1). The cycloaddition reaction was examined with N-methyl and phenyl benzaldimines. However, no cycloaddition product was observed. This result clearly reveals that the N-sulfonyl directing group is crucial for the success of the reaction. The catalytic reaction was done with [{RuCl2(p-cymene)}2] (2.5 mol %), AgSbF6 (10 mol %), and Cu(OAc)2·H2O (25 mol %) under similar reaction conditions. Product 3aa was observed in 90% yield. Since AgSbF6 is highly moisture- and air-sensitive, it has to be handled under an inert atmosphere. It is important to note that the air-stable [(p-cymene)Ru(CH3CN)3][SbF6]2 complex also 3747

DOI: 10.1021/acs.joc.8b00102 J. Org. Chem. 2018, 83, 3746−3755

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The Journal of Organic Chemistry Table 2. Scope of Substituted Aromatic Aldiminesa

a

All reactions were carried out using substituted aldimines 1b−k (0.33 mmol), N-ethyl maleimide (2a, 0.42 mmol), [(p-cymene)Ru(CH3CN)3][SbF6]2 (5 mol %), Cu(OAc)2.H2O (25 mol %) in 1,2-dichloroethane (3.0 mL) at 90 °C for 16 h. bIsolated yield.

Scheme 3. Regioselective Studies

The reaction of N-sulfonyl 2-naphthylaldimine (1l) with 2a under similar reaction conditions provided product 3la in 60% yield, in which the C−H bond activation takes place at the C3 position selectively. N-Sulfonyl 3,4-dimethoxy benzaldimine (1m) reacted with 2a, yielding product 3ma in 75% yield selectively, in which the C−H bond activation takes place at the C6 position. Similarly, meta methoxy 1n provided the expected cyclized product 3na in 65% yield. In the reaction, the C−H bond activation takes place at the C6 position of 1n. The scope of cycloaddition reaction was examined with N-substituted maleimides and dimethyl maleate (Scheme 4). N-Methyl, benzyl, phenyl, cyclohexyl, tert-butyl, and CH2CH2Ph

maleimides (2b−g) reacted efficiently with benzaldimines 1a or 1i, yielding the expected cycloaddition products 3ab, 3ac, 3id, 3ae, 3af, and 3ag in 78, 72, 85, 82, 70 and 72% yields, respectively. Similarly, the 4-anisole substituent at the N-position of maleimide 2h was also effectively involved in the reaction, affording product 3ah in 62% yield. The reaction of 1a with dimethyl maleate (2i) under similar reaction conditions gave ortho alkylated benzaldehyde 3ai in 35% yield. In the reaction, cycloaddition did not proceed due to the prior hydrolysis of the imine group. It is important to note that the tosyl group of 1-aminoindanes 3 can be easily removed in the presence of SmI2.7e 3748

DOI: 10.1021/acs.joc.8b00102 J. Org. Chem. 2018, 83, 3746−3755

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The Journal of Organic Chemistry Scheme 4. Scope of Maleimides

Scheme 5. Proposed Mechanism

intermediate 5. Coordinative syn insertion of maleimide 2 into the Ru−carbon bond of intermediate 5 gives a seven-membered ruthenacycle intermediate 6. The intramolecular nucleophilic addition of a C−Ru bond of intermediate 6 into the electrophilic CN bond gives intermediate 7. Protonation of the N−Ru bond of intermediate 8 with AcOH provides product 3

A convincing reaction mechanism is proposed to account for the present cycloaddition reaction (Scheme 5). An air-stable [(p-cymene)Ru(CH3CN)3][SbF6]2 reacts with Cu(OAc)2, giving an active ruthenium(II) species 4. The coordination of the lone pair of nitrogen atom of aldimine 1 with a ruthenium species 4, followed by ortho-metalation, provides a five-membered ruthenacycle 3749

DOI: 10.1021/acs.joc.8b00102 J. Org. Chem. 2018, 83, 3746−3755

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The Journal of Organic Chemistry

an active catalyst [(p-cymene)Ru(CH3CN)(OAc)]+[SbF6]− (4). The first step is the cleavage of the C−H bond by acetate moiety to form a five membered ruthenacycle intermediate 5. The energy barrier for the C−H activation step is found to be slightly endergonic by 18.6 kcal·mol−1. It indicates that the formation of ruthenacycle intermediate 5 is thermodynamically feasible by the loss of acetic acid. The insertion of maleimide 2b into the ruthenacycle intermediate 5 to give intermediate 6 is calculated to be exergonic by 14.8 kcal·mol−1. The formation of η2-imine coordinated ruthenacycle 7 from intermediate 6 requires only 2.6 kcal·mol−1. Addition of acetic acid to ruthenacycle 7 induces the intramolecular nucleophilic addition of the C−Ru bond of intermediate 7 into the electrophilic CN bond to give intermediate 8. Protonation of the N−Ru bond of intermediate 8 by coordinated AcOH provides product 3 and regenerates an active ruthenium species 4. Throughout the catalytic cycle, the role of ligand para-cymene was vital for maintaining the electron count around the ruthenium atom. Overall, the calculated energy barriers between the two steps and structural isolation of the key intermediate 5 clearly indicate that the proposed mechanism in Scheme 5 is the most favorable process.

and regenerates an active ruthenium species 4. Another possibility for the formation of the final product is the insertion of a CN bond into the Ru−C bond of intermediate 7 can take place first, then protonation with CH3COOH will cleave the Ru−N bond. To prove the formation of intermediate 5 in the reaction, a stoichiometric amount of [{RuCl2(p-cymene)}2] was treated with benzaldimine 1b and Cu(OAc)2·H2O (2.0 equiv) in ClCH2CH2Cl at 90 °C for 8 h (Scheme 6). As expected, intermediate 5b was Scheme 6. Intermediate Isolation

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CONCLUSION In conclusion, we have described an efficient synthesis of 1-aminoindanes via a ruthenium(II)-catalyzed, redox-free cycloaddition of N-sulfonyl benzaldimines with maleimides. The present reaction was compatible with various functional group substituted aromatic aldimines and maleimides. In the whole catalytic cycle, a ruthenium with +2 oxidation is involved. Thus, an oxidant was avoided to regenerate the catalyst. An air-stable ruthenium complex was used for the catalytic reaction. The proposed mechanism was strongly supported by the isolation of a key five-membered ruthenacycle intermediate. Further, the feasibility of the proposed mechanism was proved by the density functional theory calculations.

isolated in 69% yield and confirmed by 1H, 13C NMR and mass spectroscopy. The structure of intermediate 5b was further confirmed by a single-crystal X-ray analysis (Figure 2). Further,

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EXPERIMENTAL SECTION

General Information. All reactions were carried out under the N2 atmosphere in flame-dried glassware. Syringes which were used to transfer anhydrous solvents or reagents were purged with nitrogen prior to use (three times). Dry solvents were used for the reaction. Column chromatographical purifications were performed using SiO2 (120−200 mesh ASTM) from Merck if not indicated otherwise. Abbreviations for signal coupling are as follows: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet. Starting materials: Imines, [{RuCl2(pcymene)}2] and [(p-cymene)Ru(CH3CN)3][SbF6]2 were prepared according to literature procedures.10 Commercially available metal salts and other chemicals were purchased from Sigma-Aldrich and Spectrochem. Pvt. Ltd., India, and used without further purification. General Procedure for the Cycloaddition Reaction. A 15 mL pressure tube with septum containing [(p-cymene)Ru(CH3CN)3][SbF6]2 (5.0 mol %), Cu(OAc)2·H2O (25 mol %), and aromatic aldimine 1 (0.33 mmol) was evacuated and purged with nitrogen gas three times. To the tube was then added maleimide 2 (0.43 mmol) dissolved in 1.0 mL of DCE, followed by addition of DCE (2.0 mL) via syringe, and again the reaction mixture was purged with nitrogen gas three times. After that, the septum was taken out and immediately a screw cap was used to cover the tube. The reaction mixture was allowed to stir at 90 °C for 16 h. Then, the reaction mixture was diluted with CH2Cl2, and filtered through Celite, and the filtrate was concentrated. The crude residue was purified through a silica gel column using petroleum ether and ethyl acetate as eluent to give pure product 3. Procedure for the Preparation of Metalacycle 5b. A 15 mL Schlenk flask with septum containing [(p-cymene)Ru(CH3CN)3][SbF6]2 (120 mg, 0.14 mmol), Cu(OAc)2·H2O (58 mg, 0.28 mmol), and

Figure 2. ORTEP drawing (50% probability ellipsoids) of the ruthenacycle 5b (CCDC. 1588814). Omitted for clarity: counterion (SbF6), all H atoms.

intermediate 5b was treated with 2a in ClCH2CH2Cl at 90 °C for 16 h, giving product 3ba in 75% yield. This result clearly indicates that the catalytic reaction proceeds via intermediate 5. To understand the reaction mechanism, we have performed the theoretical calculations for the reaction of N-sulfonyl benzaldimine 1a with maleimide 2b in the presence of a ruthenium catalyst (Figure 3; the optimized structures and related information are given in the Supporting Information). For ease of calculation, N-benzylidene-p-tolylsulfonamide has been reduced to N-benzylidenemethanesulfonamide. It has been observed the good agreement between the calculated structural parameter with the experimentally observed structural parameters of key intermediate 5a (see the Supporting Information). The acetate moiety of copper complex Cu(OAc)2·H2O replaces two CH3CN and eliminates one of the counterions [SbF6]− to generate in situ 3750

DOI: 10.1021/acs.joc.8b00102 J. Org. Chem. 2018, 83, 3746−3755

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The Journal of Organic Chemistry

Figure 3. Gibbs free energy profile (kcal/mol) obtained at the BP86/6-31G*, SDD(Ru) level of theory in DCE solvent. (1 H, d, J = 7.4 Hz), 3.65 (1 H, d, J = 7.5 Hz), 3.42 (2 H, q, J = 7.2 Hz), 2.45 (3 H, s), 1.05 (3 H, t, J = 7.2 Hz). 13C NMR (126 MHz, CDCl3): δ 176.3, 175.9, 143.9, 139.5, 138.0, 137.0, 130.1, 129.8, 129.5, 127.5, 125.8, 125.3, 60.2, 52.8, 50.2, 34.0, 21.6, 12.8. HRMS (ESI-QTOF) m/z: [M + H]+ Calcd for (C20H21N2O4S) 385.1220; Found 385.1223. N-((3aS,8S,8aR)-2-Ethyl-5-methoxy-1,3-dioxo-1,2,3,3a,8,8a-hexahydroindeno[1,2-c]pyrrol-8-yl)-4-methylbenzenesulfonamide (3ba).

benzaldimine 1b (42 mg, 0.14 mmol) was evacuated and purged with nitrogen gas three times. To the tube was then added DCE (10 mL) via syringes, and again the reaction mixture was purged with nitrogen gas three times. After that, the septum was taken out and immediately a condenser was fixed. The reaction mixture was allowed to stir at 90 °C for 8 h. Then, the reaction mixture was diluted with CH2Cl2, filtered off by a Celite pad, and washed with CH2Cl2 (2 × 5 mL). The filtrate was concentrated in vacuo to 2−3 mL and ether 10 mL was added to get yellow-orange color intermediate 5b in 69% yield. 1H (400 MHz, CDCl3): δ 8.86 (1 H, s), 7.83 (2 H, d, J = 8.3), 7.76 (1 H, d, J = 8.6), 7.72 (1 H, d, J = 2.3), 7.42 (2 H, d, J = 8.1), 6.73 (1 H, dd, J = 8.6, 2.3), 6.13 (1 H, d, J = 5.8), 5.90 (1 H, d, J = 6.2), 5.59 (1 H, d, J = 7.0), 5.45−5.38 (1 H, m), 4.04 (3 H, s), 2.47 (3 H, s), 2.41−2.36 (1 H, m), 2.11 (3 H, s), 1.74 (3 H, s), 1.02 (3 H, d, J = 7), 0.78 (3 H, d, J = 7). 13 C (126 MHz, CDCl3): δ 207.1, 177.8, 146.2, 137.7, 135.8, 130.1, 128.9, 123.7, 114.4, 96.5, 93.6, 85.5, 83.6, 56.4, 53.5, 31.0, 23.8, 21.8, 20.9, 19.0. HRMS (ESI-QTOF) m/z: [M + H]+ Calcd for (C25H29NO3RuS) 525.0911; Found 525.0919. Computational Details. The geometry of all molecules was optimized using the BP86 density functional theory.11 The valence orbitals of ruthenium were described using the SDD basis set, and nonmetal centers were described using the 6-31G* basis set. Vibrational frequency calculations were performed on these optimized structures to confirm the minimum energy geometries by observing all positive frequencies and obtained the zero-point energy (ZPE), and thermal correction. A solvent correction (for DCE) was performed using the polarized continuum model (PCM).12 The energy profiles of the reaction pathways are presented as Gibbs free energy changes (ΔG’s) involving zero-point vibrational energy and thermal corrections obtained at 298.15 K and 1 atm pressure. All of these computations were carried out using the Gaussian 09 program (revision A.02).13 Spectral Data of All Compounds. N-((3aS,8S,8aR)-2-Ethyl-1,3dioxo-1,2,3,3a,8,8a-hexahydroindeno[1,2-c]pyrrol-8-yl)-4-methylbenzenesulfonamide (3aa).

White solid; eluent (20% ethyl acetate in hexane).The reaction scale is 95 mg (3ba), 109 mg of product was isolated, and yield is 80%. 1 H NMR (400 MHz, CDCl3): δ 7.86 (2 H, d, J = 8.2 Hz), 7.35 (2 H, d, J = 8.0 Hz), 7.03 (1 H, d, J = 2.0 Hz), 6.95 (1 H, d, J = 8.5 Hz), 6.83−6.75 (1 H, m), 5.02 (1 H, d, J = 7 Hz), 4.91 (1 H, d, J = 7.0 Hz), 4.34 (1 H, d, J = 7.4 Hz), 3.80 (3 H, s), 3.67 (1 H, dd, J = 7.4, 1.2 Hz), 3.43 (2 H, q, J = 7.2 Hz), 2.45 (3 H, s), 1.06 (3 H, t, J = 7.2 Hz). 13C NMR (101 MHz, CDCl3): δ 176.5, 176.0, 161.5, 143.9, 139.8, 137.1, 131.4, 129.9, 127.6, 126.6, 117.2, 109.1, 77.5, 77.1, 76.8, 59.9, 55.7, 53.6, 50.4, 34.1, 21.7, 12.9. HRMS (ESI-QTOF) m/z: [M + H]+ Calcd for (C21H23N2O5S) 415.1330; Found 415.1322. N-((3aS,8S,8aR)-2-Ethyl-5-methyl-1,3-dioxo-1,2,3,3a,8,8a-hexahydroindeno[1,2-c]pyrrol-8-yl)-4-methylbenzenesulfonamide (3ca).

White solid; eluent (20% ethyl acetate in hexane).The reaction scale is 90 mg (3ca), 98 mg of product was isolated, and yield is 75%. Mp: 162−164 °C. 1H NMR (400 MHz, CDCl3): δ 7.86 (2 H, d, J = 8.2 Hz), 7.34 (3 H, d, J = 7.8 Hz), 7.04 (1 H, d, J = 7.8 Hz), 6.94 (1 H, d, J = 7.8 Hz), 5.03 (1 H, d, J = 7.0 Hz), 4.96 (1 H, d, J = 7.0 Hz), 4.32 (1 H, d, J = 7.4 Hz), 3.64 (1 H, dd, J = 7.4, 1.1 Hz), 3.41 (2 H, q, J = 7.2 Hz), 2.45 (3 H, s), 2.33 (3 H, s), 1.05 (3 H, t, J = 7.2 Hz). 13C NMR (101 MHz, CDCl3): δ 176.6, 176.2, 144.0, 140.6, 138.2, 137.1, 136.7, 130.7, 129.9, 127.6, 125.8, 125.5, 77.5, 77.1, 76.8, 60.1, 53.2, 50.2, 34.1, 21.7, 21.5, 13.0. HRMS (ESI-QTOF) m/z: [M + H]+ Calcd for (C21H23N2O4S) 399.1378; found 399.1367.

White solid; eluent (20% ethyl acetate in hexane).The reaction scale is 85.5 mg (3aa), 116 mg of product was isolated, and yield is 92%. 1H NMR (500 MHz, CDCl3): δ 7.86 (2 H, d, J = 8.0 Hz), 7.55 (1 H, d, J = 7.7 Hz), 7.35 (3 H, d, J = 8 Hz), 7.26 (1 H, d, J = 6.7 Hz), 7.09 (1 H, d, J = 7.7 Hz), 5.09 (1 H, d, J = 7.2 Hz), 5.03 (1 H, d, J = 7.2 Hz), 4.38 3751

DOI: 10.1021/acs.joc.8b00102 J. Org. Chem. 2018, 83, 3746−3755

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The Journal of Organic Chemistry

Mp: 100−102 °C. 1H NMR (500 MHz, DMSO-D6): δ 8.43 (d, J = 8.4 Hz, 1H), 7.82 (d, J = 8.2 Hz, 2H), 7.47 (s, 1H), 7.45 (s, 1H), 7.39 (dd, J = 8.2, 1.7 Hz, 1H), 7.14 (d, J = 8.2 Hz, 1H), 4.98 (d, J = 8.2 Hz, 1H), 4.41 (d, J = 7.6 Hz, 1H), 3.49 (dd, J = 7.6, 1.6 Hz, 1H), 3.31 (q, J = 7.2 Hz, 2H), 2.46 (s, 3H), 0.97 (t, J = 7.2 Hz, 3H). 13C NMR (126 MHz, DMSO-D6): δ 176.2, 175.6, 142.7, 140.3, 139.9, 138.5, 133.7, 129.6, 129.6, 129.5, 129.0, 127.5, 126.6, 126.5, 124.3, 124.2, 58.8, 52.4, 50.0, 33.2, 20.9, 12.4. HRMS (ESI-QTOF) m/z: [M + Na]+ Calcd for (C20H19ClN2O4SNa) 441.0651; Found 441.0650. N-((3aS,8S,8aR)-2-Ethyl-5-fluoro-1,3-dioxo-1,2,3,3a,8,8a-hexahydroindeno[1,2-c]pyrrol-8-yl)-4-methylbenzenesulfonamide (3ha).

N-((3aS,8S,8aR)-2-Ethyl-5-isopropyl-1,3-dioxo-1,2,3,3a,8,8a-hexahydroindeno[1,2-c]pyrrol-8-yl)-4-methylbenzenesulfonamide (3da).

Colorless solid; eluent (20% ethyl acetate in hexane).The reaction scale is 99 mg (3da), 126 mg of product was isolated, and yield is 90%. Mp: 134−136 °C. 1H NMR ((500 MHz, CDCl3)): δ 7.90−7.80 (2 H, m), 7.39 (1 H, s), 7.32 (2 H, d, J = 7.0 Hz), 7.09 (1 H, d, J = 8.0 Hz), 6.97 (1 H, d, J = 8.0 Hz), 5.15 (1 H, d, J = 7.0 Hz), 5.05 (1 H, d, J = 6.8 Hz), 4.36 (1 H, d, J = 7.2 Hz), 3.66 (1 H, d, J = 7.4 Hz), 3.46−3.35 (2 H, m), 2.95−2.83 (1 H, m), 2.44 (3 H, s), 1.24−1.18 (6 H, m), 1.09−1.03 (3 H, m). 13C NMR (126 MHz, CDCl3): δ 176.5, 176.0, 151.5, 143.7, 138.2, 137.2, 137.0, 129.8, 127.9, 127.5, 125.5, 123.1, 60.0, 53.2, 50.1, 34.0, 33.9, 24.0, 23.7, 21.5, 12.8. HRMS (ESI-QTOF) m/z: [M + H]+ Calcd for (C23H27N2O4S) 427.1691; Found 427.1666. N-((3aS,8S,8aR)-2-Ethyl-5-(methylthio)-1,3-dioxo-1,2,3,3a,8,8a-hexahydroindeno[1,2-c]pyrrol-8-yl)-4-methylbenzenesulfonamide (3ea).

Colorless solid; eluent (17% ethyl acetate in hexane).The reaction scale is 93 mg (3ha), 79 mg of product was isolated, and yield is 60%. Mp: 138−140 °C. 1H NMR (500 MHz, CDCl3): δ 7.83 (2 H, d, J = 7.8 Hz), 7.34 (2 H, d, J = 7.8 Hz), 7.24 (1 H, d, J = 8.2 Hz), 7.06 (1 H, dd, J = 8.2, 5.0 Hz), 6.94 (1 H, t, J = 8.2 Hz), 5.05 (2 H, dd, J = 16.9, 7.4 Hz), 4.36 (1 H, d, J = 7.4 Hz), 3.67 (1 H, d, J = 7.4 Hz), 3.43 (2 H, q, J = 7.2 Hz), 2.45 (3 H, s), 1.06 (3 H, t, J = 7.2 Hz). 13C NMR (126 MHz, CDCl3): δ 175.9, 175.2, 164.8 (1JC‑F = 249.5 Hz), 143.9, 140.2 (3JC‑F = 8.8 Hz), 137.1, 135.1, 129.8, 127.4, 117.2 (2JC‑F = 24 Hz), 112.3 (2JC‑F = 24 Hz), 59.6, 53.4, 50.1, 34.1, 21.5, 12.7. HRMS (ESI-QTOF) m/z: [M + H]+ Calcd for (C20H20FN2O4S) 403.1127; Found 403.1159. N-((3aS,8S,8aR)-2-Ethyl-7-methyl-1,3-dioxo-1,2,3,3a,8,8a-hexahydroindeno[1,2-c]pyrrol-8-yl)-4-methylbenzenesulfonamide (3ia).

Pale yellow solid; eluent (20% ethyl acetate in hexane).The reaction scale is 102 mg (3ea), 89 mg of product was isolated, and yield is 55%. 1 H NMR (400 MHz, CDCl3): δ 7.82 (2 H, s), 7.39−7.32 (3 H, m), 7.08 (1 H, dd, J = 8.2 Hz), 6.95 (1 H, d, J = 8.2 Hz), 5.20 (1 H, d, J = 7.4 Hz), 5.07−5.01 (1 H, m), 4.35 (1 H, d, J = 7.4 Hz), 3.63 (1 H, dd, J = 7.4 Hz), 3.42 (2 H, q, J = 7.2 Hz), 2.46 (6 H), 1.06 (3 H, t, J 7.2 Hz). 13C NMR (101 MHz, CDCl3): δ 176.4, 175.9, 144.0, 141.8, 138.9, 137.1, 136.0, 129.9, 129.84, 127.5, 127.5, 126.5, 126.0, 121.8, 59.9, 53.1, 50.2, 34.2, 21.7, 21.6, 15.5, 12.9. HRMS (ESIQTOF) m/z: [M + Na]+ Calcd for (C21H22N2O4S2Na) 453.0918; Found 453.0906. N-((3aS,8S,8aR)-5-Bromo-2-ethyl-1,3-dioxo-1,2,3,3a,8,8a-hexahydroindeno[1,2-c]pyrrol-8-yl)-4-methylbenzenesulfonamide (3fa).

Colorless solid; eluent (20% ethyl acetate in hexane).The reaction scale is 90 mg (3ia), 118 mg of product was isolated, and yield is 90%. Mp: 180−182 °C. 1H NMR (400 MHz, CDCl3): δ 7.78 (2 H, d, J = 8.2 Hz), 7.29 (1 H, dd, J = 7.8 Hz), 7.21−7.13 (2 H, m), 6.96 (1 H, d, J = 7.0 Hz), 5.03 (1 H, d, J = 7.0 Hz), 4.68 (1 H, d, J = 7.0 Hz), 4.31 (1 H, d, J = 7.2 Hz), 3.56 (1 H, dd, J = 7.2 Hz), 3.34 (2 H, q, J = 7.2 Hz), 2.37 (3 H, s), 1.95 (3 H, s), 0.98 (3 H, t, J = 7.2 Hz). 13C NMR (101 MHz, CDCl3): δ 176.6, 176.2, 144.0, 138.6, 137.4, 136.8, 136.3, 130.9, 130.6, 129.9, 127.7, 122.8, 59.4, 52.8, 50.4, 34.1, 21.7, 18.1, 12.9. HRMS (ESI-QTOF) m/z: [M + H]+ Calcd for (C21H22N2O4S) 399.1378; Found 399.1383. Crystal structure of the above compound is recorded and presented here. N-((3aS,8S,8aR)-2-Ethyl-7-fluoro-1,3-dioxo-1,2,3,3a,8,8a-hexahydroindeno[1,2-c]pyrrol-8-yl)-4-methylbenzenesulfonamide (3ja).

Colorless solid; eluent (25% ethyl acetate in hexane).The reaction scale is 111 mg (3fa), 85 mg of product was isolated, and yield is 56%. Mp: 176−178 °C. 1H NMR (400 MHz, DMSO-D6): δ 8.39 (d, J = 8.0 Hz, 1H), 7.77 (d, J = 8.0 Hz, 2H), 7.54 (s, 1H), 7.46 (d, J = 8.1 Hz, 1H), 7.40 (d, J = 8.0 Hz, 2H), 7.03 (d, J = 8.2 Hz, 1H), 4.93 (d, J = 7.6 Hz, 1H), 4.38 (d, J = 7.6 Hz, 1H), 3.44 (d, J = 6.3 Hz, 1H), 3.27 (d, J = 7.2 Hz, 2H), 2.40 (s, 3H), 0.92 (t, J = 7.2 Hz, 3H). 13C NMR (101 MHz, DMSO-D6): δ 176.2, 175.6, 142.8, 140.7, 140.2, 138.5, 131.8, 129.6, 127.9, 127.2, 126.6, 122.1, 59.0, 52.3, 50.0, 33.2, 21.0, 12.4. HRMS (ESI-QTOF) m/z: [M + H]+ Calcd for (C20H20BrN2O4S) 463.0327; Found 463.0318. N-((3aS,8S,8aR)-5-Chloro-2-ethyl-1,3-dioxo-1,2,3,3a,8,8a-hexahydroindeno[1,2-c]pyrrol-8-yl)-4-methylbenzenesulfonamide (3ga).

Semi-solid (Yellow); eluent (15% ethyl acetate in hexane).The reaction scale is 93 mg (3ja), 74 mg of product was isolated, and yield is 56%. Mp: 132−134 °C. 1H NMR (400 MHz, CDCl3): δ 7.75 (2 H, d, J = 8.2 Hz), 7.37 (1 H, d, J = 7.6 Hz), 7.30 (3 H, dd, J = 8.2 Hz), 6.81 (1 H, t, J = 8.4 Hz), 5.16−5.04 (2 H, m), 4.53 (1 H, d, J = 7.4 Hz), 4.03 (1 H, d, J = 7.4 Hz), 3.44 (2 H, q, J = 7.2 Hz), 2.43 (3 H, s), 1.07 (3 H, t, J = 7.2 Hz). 13C NMR (126 MHz, CDCl3): δ 176.2, 175.5, 160.1 (1JC‑F = 253 Hz), 143.7, 141.58 (3JC‑F = 4.0 Hz), 136.2, 132.46 (3JC‑F = 7.2 Hz), 129.62, 127.5, 125.6 (2JC‑F = 16.8 Hz), 121.0 (4JC‑F = 3.4 Hz), 115.6 (2JC‑F = 19.1 Hz), 57.4, 53.3, 50.7, 34.0, 21.5, 12.8. HRMS (ESI-QTOF) m/z: [M + H]+ Calcd for (C20H20FN2O4S) 403.1127; Found 403.1159.

Colorless solid; eluent (25% ethyl acetate in hexane).The reaction scale is 97 mg (3ga), 84 mg of product was isolated, and yield is 61%. 3752

DOI: 10.1021/acs.joc.8b00102 J. Org. Chem. 2018, 83, 3746−3755

Article

The Journal of Organic Chemistry N-((6bS,9aR,10S)-8-Ethyl-7,9-dioxo-6b,7,8,9,9a,10-hexahydrobenzo[4,5]indeno[1,2-c]pyrrol-10-yl)-4-methylbenzenesulfonamide (3ka).

Colorless solid; eluent (20% ethyl acetate in hexane).The reaction scale is 95 mg (3na), 89 mg of product was isolated, and yield is 65%. 1 H NMR (400 MHz, CDCl3): δ 7.80 (2 H, d, J = 8.2 Hz), 7.39 (1 H, d, J = 8.5 Hz), 7.31 (2 H, d, J = 8.1 Hz), 6.84 (1 H, dd, J = 8.4 Hz, 2.4), 6.50 (1 H, d, J = 2.2 Hz), 5.49 (1 H, d, J = 7.6 Hz), 5.06 (1 H, d, J = 7.4 Hz), 4.30 (1 H, d, J = 7.2 Hz), 3.65 (3 H, s), 3.58 (1 H, dd, J = 7.4 Hz, 1.2), 3.39 (2 H, q, J = 7.2 Hz), 2.44 (3 H, s), 1.03 (3 H, t, J = 7.2 Hz). 13C NMR (101 MHz, CDCl3): δ 176.7, 176.5, 160.9, 143.9, 141.0, 137.4, 129.9, 129.9, 127.4, 126.0, 117.4, 109.7, 60.4, 55.5, 53.5, 49.6, 34.0, 21.7, 12.9. HRMS (ESI-QTOF) m/z: [M + H]+ Calcd for (C21H23N2O5S) 415.1327; Found 415.1347. 4-Methyl-N-((3aS,8S,8aR)-2-methyl-1,3-dioxo-1,2,3,3a,8,8a-hexahydroindeno[1,2-c]pyrrol-8-yl)benzenesulfonamide (3ab).

Colorless solid; eluent (20% ethyl acetate in hexane).The reaction scale is 102 mg (3ka), 114 mg of product was isolated, and yield is 80%. Mp: 194−196 °C. 1H NMR (500 MHz, CDCl3): δ 7.80 (4 H, dd, J = 8.0, 6.6 Hz), 7.61 (1 H, d, J = 8.4 Hz), 7.45 (2 H, t, J = 8.0 Hz), 7.39 (1 H, d, J = 8.4 Hz), 7.25 (2 H, dd, J = 8.0, 6.6 Hz), 5.58 (1 H, d, J = 6.8 Hz), 5.15 (1 H, d, J = 6.8 Hz), 4.53 (1 H, d, J = 6.8 Hz), 3.71 (1 H, d, J = 6.8 Hz), 3.44−3.36 (2 H, m), 2.41 (3 H, s), 1.07−0.97 (3 H, m). 13C NMR (126 MHz, CDCl3): δ 176.5, 176.1, 143.9, 136.8, 136.6, 134.2, 134.0, 131.5, 129.8, 129.3, 128.8, 127.6, 126.6, 123.7, 122.1, 59.5, 53.1, 51.3, 34.0, 21.6, 12.9. HRMS (ESI-QTOF) m/z: [M + H]+ Calcd for (C24H23N2O4S) 435.1378; Found 435.1377. N-((3aS,10S,10aR)-2-Ethyl-1,3-dioxo-1,2,3,3a,10,10a-hexahydrobenzo[5,6]indeno[1,2-c]pyrrol-10-yl)-4-methylbenzenesulfonamide (3la).

White solid; eluent (20% ethyl acetate in hexane).The reaction scale is 85 mg (3ab), 95 mg of product was isolated, and yield is 78%. Mp: 146−148 °C. 1H NMR (400 MHz, CDCl3): δ 7.81 (d, J = 8.3 Hz, 2H), 7.49 (d, J = 7.6 Hz, 1H), 7.38−7.26 (m, 3H), 7.21 (t, J = 7.5 Hz, 1H), 7.09 (d, J = 7.6 Hz, 1H), 5.57 (d, J = 7.6 Hz, 1H), 5.08 (d, J = 7.6 Hz, 1H), 4.39 (d, J = 7.4 Hz, 1H), 3.56 (dd, J = 7.5, 1.2 Hz, 1H), 2.82 (s, 3H), 2.44 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 176.7, 176.4, 143.8, 139.8, 137.9, 137.1, 130.0, 129.9, 129.5, 127.5, 126.0, 125.3, 60.2, 52.8, 50.3, 25.1, 21.7. HRMS (ESI-QTOF) m/z: [M + Na]+ Calcd for (C19H18N2O4SNa) 393.0885; Found 393.0870. N-((3aS,8S,8aR)-2-Benzyl-1,3-dioxo-1,2,3,3a,8,8a-hexahydroindeno[1,2-c]pyrrol-8-yl)-4-methylbenzenesulfonamide (3ac).

Colorless solid; eluent (20% ethyl acetate in hexane).The reaction scale is 102 mg (3la), 86 mg of product was isolated, and yield is 60%. Mp: 180−182 °C. 1H NMR (400 MHz, CDCl3): δ 8.04 (1 H, s), 7.84 (1 H, d, J = 8.0 Hz), 7.81 (2 H, d, J = 8.2 Hz), 7.65 (1 H, d, J = 8.0 Hz), 7.48 (3 H, dt, J = 8.2 Hz), 7.26 (2 H, d, J = 5.4 Hz), 5.24 (1 H, d, J 6.7 Hz), 5.04 (1 H, d, J = 6.6 Hz), 4.56 (1 H, d, J = 7.6 Hz), 3.82 (1 H, dd, J = 7.6, 1.4 Hz), 3.43 (2 H, q, J 7.2), 2.41 (3 H, s), 1.04 (3 H, t, J = 7.2 Hz). 13C NMR (126 MHz, DMSO-D6): δ 181.7, 181.2, 147.9, 144.7, 144.0, 141.2, 138.6, 138.4, 134.9, 134.8, 133.0, 131.9, 131.8, 130.3, 130.2, 128.4, 64.0, 58.0, 54.9, 38.4, 26.2, 17.7. HRMS (ESI-QTOF) m/z: [M + H]+ Calcd for (C24H23N2O4S) 435.1378; Found 435.1400. N-((3aS,8S,8aR)-2-Ethyl-5,6-dimethoxy-1,3-dioxo-1,2,3,3a,8,8a-hexahydroindeno[1,2-c]pyrrol-8-yl)-4-methylbenzenesulfonamide (3ma).

White solid; eluent (20% ethyl acetate in hexane).The reaction scale is 85 mg (3ac), 105 mg of product was isolated, and yield is 72%. Mp: 108−110 °C. 1H NMR (500 MHz, CDCl3): 7.86 (d, J = 8.0 Hz, 2H), 7.56 (d, J = 7.7 Hz, 1H), 7.34 (d, J = 8.1 Hz, 3H), 7.28−7.20 (m, 6H), 7.07 (d, J = 7.7 Hz, 1H), 5.10 (d, J = 7.0 Hz, 1H), 4.87 (d, J = 7.0 Hz, 1H), 4.51 (q, J = 14.2 Hz, 2H), 4.40 (d, J = 7.4 Hz, 1H), 3.67 (d, J = 7.4 Hz, 1H), 2.45 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 176.1, 175.7, 143.9, 139.5, 137.9, 136.9, 135.2, 130.2, 129.9, 129.6, 128.6, 128.4, 127.9, 127.5, 125.7, 125.4, 60.2, 52.9, 50.2, 42.5, 21.6. HRMS (ESI-QTOF) m/z: [M + Na]+ Calcd for (C25H22N2O4SNa) 469.1198; Found 469.1181. 4-Methyl-N-((3aS,8S,8aR)-7-methyl-1,3-dioxo-2-phenyl1,2,3,3a,8,8a-hexahydroindeno[1,2-c]pyrrol-8-yl)benzenesulfonamide (3id).

Colorless solid; eluent (20% ethyl acetate in hexane).The reaction scale is 98 mg (3ma), 110 mg of product was isolated, and yield is 75%. Mp: 154−156 °C. 1H NMR (500 MHz, DMSO-D6): δ 8.28 (1 H, d, J = 8.2 Hz), 7.74 (2 H, d, J = 8.2 Hz), 7.40 (2 H, d, J = 8.0 Hz), 6.87 (1 H, s), 6.29 (1 H, s), 4.88 (1 H, d, J = 8.0), 4.24 (1 H, d, J = 7.2 Hz), 3.74 (3 H, s), 3.53 (3 H, s), 3.47 (1 H, d, J = 7.2 Hz), 3.27 (2 H, q, J = 7.0 Hz), 2.38 (3 H, s), 0.92 (3 H, t, J = 7.0 Hz). 13C NMR (126 MHz, DMSO-D6): δ 177.2, 176.8, 150.6, 150.2, 143.1, 139.4, 132.7, 130.3, 130.1, 127.1, 109.0, 107.0, 60.1, 56.1, 55.7, 53.8, 50.5, 33.5, 21.4, 13.0. HRMS (ESI-QTOF) m/z: [M + H]+ Calcd for (C22H25N2O6S) 445.1433; Found 445.1407. N-((3aS,8S,8aR)-2-Ethyl-6-methoxy-1,3-dioxo-1,2,3,3a,8,8a-hexahydroindeno[1,2-c]pyrrol-8-yl)-4-methylbenzenesulfonamide (3na).

White solid; eluent (20% ethyl acetate in hexane).The reaction scale is 90 mg (3id), 125 mg of product was isolated, and yield is 85%. 1 H NMR (400 MHz, CDCl3): δ 7.86 (2 H, d, J = 8.2 Hz), 7.38 (6 H, tdd, J = 14.0 Hz, 13.5, 5.9), 7.28 (1 H, s), 7.18−7.12 (2 H, m), 7.07 (1 H, d, J = 7.6 Hz), 5.20 (1 H, d, J = 7.0 Hz), 4.79 (1 H, d, J = 7.0 Hz), 4.55 (1 H, d, J = 7.2 Hz), 3.84 (1 H, dd, J = 7.4 Hz), 2.44 (3 H, s), 2.05 (3 H, s). 13C NMR (101 MHz, CDCl3): δ 176.2, 175.8, 144.1, 138.7, 137.7, 137.09, 131.7, 131.1, 130.8, 130.0, 129.2, 128.8, 127.8, 126.4, 123.0, 59.8, 52.9, 50.5, 21.5, 18.2. HRMS (ESIQTOF) m/z: [M + H]+ Calcd for (C25H23N2O4S) 447.1378; Found 447.1388. 3753

DOI: 10.1021/acs.joc.8b00102 J. Org. Chem. 2018, 83, 3746−3755

Article

The Journal of Organic Chemistry

Mp: 114−116 °C. 1H NMR (400 MHz, CDCl3): δ 7.87 (2 H, d, J = 8.4 Hz), 7.61 (1 H, d, J = 7.8 Hz), 7.41−7.28 (4 H, m), 7.13 (1 H, d, J = 7.8 Hz), 7.08−7.02 (2 H, m), 6.93−6.88 (2 H, m), 5.19 (1 H, d, J = 7.0 Hz), 5.06 (1 H, d, J = 7.2 Hz), 4.53 (1 H, d, J = 7.6 Hz), 3.83 (1 H, dd, J = 7.6 Hz, 1.3), 3.79 (3 H, s), 2.44 (3 H, s). 13C NMR (101 MHz, CDCl3): δ 176.1, 171.1, 159.7, 144.1, 139.9, 138.1, 137.0, 130.5, 130.1, 130, 127.8, 127.7, 126.1, 125.7, 114.6, 6, 55.7, 53.0, 50.4, 21.9. HRMS (ESI-QTOF) m/z: [M + Na]+ Calcd for (C25H22N2O5SNa) 485.1147; Found 485.1154. Dimethyl 2-(2-Formylphenyl)succinate (3ai).

N-((3aS,8S,8aR)-2-Cyclohexyl-1,3-dioxo-1,2,3,3a,8,8a-hexahydroindeno[1,2-c]pyrrol-8-yl)-4-methylbenzenesulfonamide (3ae).

White solid; eluent (20% ethyl acetate in hexane).The reaction scale is 82 mg (3ae), 118 mg of product was isolated, and yield is 82%. Mp: 90−92 °C. 1H NMR (400 MHz, CDCl3): δ 7.88 (d, J = 8.3 Hz, 2H), 7.55 (d, J = 7.6 Hz, 1H), 7.35 (m, 3H), 7.25 (d, J = 7.6 Hz, 1H), 7.08 (d, J = 7.6 Hz, 1H), 5.08 (d, J = 7.0 Hz, 1H), 4.77 (d, J = 7.0 Hz, 1H), 4.31 (d, J = 7.5 Hz, 1H), 3.93−6.71 (m, 1H), 3.62 (dd, J = 7.5, 1.3 Hz, 1H), 2.46 (s, 3H), 2.08−1.91 (m, 2H), 1.75 (d, J = 12.6 Hz, 2H), 1.61 (s, 2H), 1.40 (dd, J = 11.2, 7.5 Hz, 2H), 1.31−1.14 (m, 4H). 13C NMR (126 MHz, CDCl3): δ δ 176.7, 176.3, 144.0, 139.6, 138.4, 137.1, 130.3, 130.0, 129.7, 127.6, 125.8, 125.4, 60.6, 52.6, 52.1, 50.0, 28.9, 28.6, 25.8, 25.8, 25.0, 21.7. HRMS (ESI-QTOF) m/z: [M + Na]+ Calcd for (C24H26N2O4SNa) 461.1511; Found 461.1497. N-((3aS,8S,8aR)-2-(tert-butyl)-1,3-dioxo-1,2,3,3a,8,8a-hexahydroindeno[1,2-c]pyrrol-8-yl)-4-methylbenzenesulfonamide (3af).

Colorless liquid; eluent (5% ethyl acetate in hexane).The reaction scale is 85 mg (3ai), 28 mg of product was isolated, and yield is 35%. 1 H NMR ((500 MHz, CDCl3)): δ 10.20 (1 H, s), 7.85 (1 H, dd, J = 7.6 Hz), 7.56 (1 H, dd, J = 7.6 Hz), 7.51 (1 H, dd, J = 7.4 Hz), 7.38 (1 H, d, J = 7.6 Hz), 5.11 (1 H, dd, J = 8.4 Hz), 3.67 (6 H, d, J = 5.2 Hz), 3.23 (1 H, dd, J = 17.0, 8.6 Hz), 2.71 (1 H, dd, J = 17.0 Hz, 6.0). 13 C NMR (126 MHz, CDCl3): δ 192.9, 173.50, 172.4 139.80, 133.29, 131.94, 129.29, 128.12, 127.67, 52.41, 51.97, 37.61, 29.71. HRMS (ESI-QTOF) m/z: [M + H]+ Calcd for (C13H15O5) 251.0919; Found 251.0901.

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White solid; eluent (20% ethyl acetate in hexane).The reaction scale is 90 mg (3af), 95 mg of product was isolated, and yield is 70%. Mp: 150−152 °C. 1H NMR (500 MHz, CDCl3): δ 7.84 (d, J = 8.3 Hz, 2H), 7.52 (d, J = 7.8 Hz, 1H), 7.32 (dd, J = 13.2, 7.8 Hz, 3H), 7.23 (t, J = 7.6 Hz, 1H), 7.04 (d, J = 7.6 Hz, 1H), 5.07 (d, J = 7.2 Hz, 1H), 5.02 (d, J = 7.2 Hz, 1H), 4.21 (d, J = 7.7 Hz, 1H), 3.53 (dd, J = 7.7, 1.1 Hz, 1H), 2.45 (s, 3H), 1.44 (s, 9H). 13C NMR (126 MHz, CDCl3): δ 177.6, 177.2, 143.9, 139.7, 138.7, 137.2, 130.1, 129.9, 129.5, 127.5, 125.8, 125.3, 60.7, 58.7, 52.9, 50.1, 28.2, 21.7. HRMS (ESI-QTOF) m/z: [M + Na]+ Calcd for (C22H24N2O4SNa) 435.1354; Found 435.1368. N-((3aS,8S,8aR)-1,3-Dioxo-2-phenethyl-1,2,3,3a,8,8a-hexahydroindeno[1,2-c]pyrrol-8-yl)-4-methylbenzenesulfonamide (3ag).

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.8b00102. 1 H NMR and 13C NMR spectra of all compounds, CIF information: a single-crystal X-ray diffraction data for compounds 3ia and 5b, computational details, and Cartesian coordinate of all molecules (PDF) X-ray diffraction data for compound 3ia (CIF) X-ray diffraction data for compound 5b (CIF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected], mjeganmohan@iiserpune. ac.in. White solid; eluent (20% ethyl acetate in hexane).The reaction scale is 90 mg (3ag), 95 mg of product was isolated, and yield is 72%. Mp: 178−180 °C. 1H NMR (400 MHz, CDCl3): δ 7.84 (2 H, d, J = 8.3), 7.50 (1 H, d, J = 7.6), 7.34 (3 H, d, J = 7.9), 7.28 (1 H, d, J = 7.6), 7.13−6.98 (4 H, m), 6.88 (2 H, dd, J = 7.6), 4.95 (1 H, d, J = 7.3), 4.87 (1 H, d, J = 7.3), 4.30 (1 H, d, J = 7.5), 3.63 (2 H, t, J = 7.3), 3.52 (1 H, dd, J = 7.5), 2.74 (2 H, t, J = 7.2), 2.46 (3 H, s). 13C NMR (126 MHz, CDCl3): δ 176.3, 176.0, 143.9, 139.6, 138.1, 137.3, 137.2, 130.3, 130.0, 129.6, 128.8, 128.4, 127.6, 126.6, 125.9, 125.4, 60.5, 52.7, 50.1, 40.0, 33.1, 21.7. HRMS (ESI-QTOF) m/z: [M + Na]+ Calcd for (C26H24N2O4SNa) 483.1354; Found 483.1359. N-((3aS,8S,8aR)-2-(4-Methoxyphenyl)-1,3-dioxo-1,2,3,3a,8,8ahexahydroindeno[1,2-c]pyrrol-8-yl)-4-methylbenzenesulfonamide (3ah).

ORCID

Masilamani Jeganmohan: 0000-0002-7835-3928 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank the DST-SERB (EMR/2014/000978), India, for the support of this research. M.T. thanks the IIT Madras for an institute postdoctoral fellowship. B.R. thanks the CSIR for a fellowship.

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REFERENCES

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Colorless solid; eluent (20% ethyl acetate in hexane).The reaction scale is 85 mg (3ae), 94 mg of product was isolated, and yield is 62%. 3754

DOI: 10.1021/acs.joc.8b00102 J. Org. Chem. 2018, 83, 3746−3755

Article

The Journal of Organic Chemistry

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DOI: 10.1021/acs.joc.8b00102 J. Org. Chem. 2018, 83, 3746−3755