Enone Carbonyl Directed Hydroarylation of Maleimides

Changzhou University, Changzhou 213164, P. R. China. ‡ School of Chemical and Environmental Engineering, Jiangsu University of Technology, Changzhou...
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Cite This: J. Org. Chem. 2018, 83, 12086−12093

Rhodium-Catalyzed Site-Selective ortho-C−H Activation: Enone Carbonyl Directed Hydroarylation of Maleimides Jin-Tao Yu,*,† Rongzhen Chen,† Hailang Jia,‡ and Changduo Pan*,‡ †

School of Petrochemical Engineering, Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology, Changzhou University, Changzhou 213164, P. R. China ‡ School of Chemical and Environmental Engineering, Jiangsu University of Technology, Changzhou 213001, P. R. China

J. Org. Chem. 2018.83:12086-12093. Downloaded from pubs.acs.org by UNIV OF SUNDERLAND on 10/05/18. For personal use only.

S Supporting Information *

ABSTRACT: Enone carbonyl directed 1,4-addition of orthoC−H bond in chalcones to maleimides was developed under the catalysis of Rh(III). This reaction furnished a variety of chalcone-based pharmacologically useful 3-arylated succinimide derivatives in good yields with excellent selectivity.

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INTRODUCTION The catalytic C−H bond functionalization is the most promising and attractive strategy in the construction of C−C bond for their highly step-economical as well as eco-friendly in comparison to the traditional methods that required organohalides and organometallic reagents.1 Metal-catalyzed orthoC−H functionalization of arenes assisted by proper directing groups is well developed in the past decades, including the arylation, alkenylation, alkynylation, alkylation, carbonylation, etc.2 Amides, imines, oximes, pyridines, pyrimidines, azines, ketones, carboxylic acids, and others were frequently employed as efficient directing groups in those reactions. However, to the best of our knowledge, C−H functionalization reactions utilizing enone carbonyl as directing group hve rarely been reported, and the β-H activation was mostly involved. For example, Murai and Trost developed the enone carbonyl directed β-alkylation using vinylsilanes or styrene as alkyl sources catalyzed by Ru (eqs (a) and (b), Scheme 1).3 Rhcatalyzed C−H activation of enone carbonyl for the cyclization of diynes was also achieved by Shibata and Tanaka (eq (c), Scheme 1).4 To date, there was only one example described by Bakthadoss dealing with the enone carbonyl directed ortho-C− H activation for the construction of ortho-olefinated chalcones (eq (d), Scheme 1).5 Chalcones, bearing an enone carbonyl group, are an important class of compounds that exhibit various biological activities, such as anticancer, antidiabetic, anti-HIV, and anti-inflammatory.6 In addition, the enone carbonyl motif in chalcones has plenty of reactivities for further derivations.7 Succinimides, bearing a cyclic imide motif, are prevalent in many natural products such as palasimide and salfredin and also act as central functional unit in many drugs and new drug candidates with distinctive bioactivities.8 As a convenient source, maleimides, a highly electrophilic olefin, were frequently utilized in introducing the succinimide structures into organic molecules to construct complex structures, particularly bioactive natural products and pharmaceutical compounds.9−13 For example, rhodium,10 ruthenium, 11 © 2018 American Chemical Society

Scheme 1. Enone Carbonyl Directed C−H Functionalizations

cobalt,12 and manganese13 catalyzed Michael-type 1,4-addition reactions have been well developed in hydroarylation of maleimides via C−H bond activation to produce various 3arylated succinimides. In some cases, cascade reaction occurred leading to more complex spirocyclic structures.14 In this respect, strong coordination groups such as amide, 8aminoquinoline, oxime, azo, and N-containing heterocycles were widely used. Some weak coordination groups, such as ketone and ester, could also function as directing groups to Received: August 8, 2018 Published: September 13, 2018 12086

DOI: 10.1021/acs.joc.8b02059 J. Org. Chem. 2018, 83, 12086−12093

Article

The Journal of Organic Chemistry activate the ortho-C−H in arenes. However, enone carbonyl has never been utilized as directing group in the hydroarylation of maleimides. The protocol dealing with the combination of two bioactive fragments, chalcone and maleimide, together may produce compounds posse novel bioactivities, thus needs to be explored. Therefore, we devoted our attention toward the selective hydroarylation of maleimides with chalcones via enone carbonyl directed ortho-C−H activation to produce a novel class of structures with potential bioactivities.

After obtaining of the optimized reaction conditions, we started to explore the substrates scopes of the reaction (Charts 1 and 2). As expected, different substituents at the aryl group Chart 1. Substrates Scope of Chalcones and Maleimidesa

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RESULTS AND DISCUSSION Bearing this idea in mind, we started our investigation by choosing chalcone 1a and N-methylmaleimide 2a as benchmark substrates to explore the best reaction conditions, and some of them were listed in Table 1. We first conducted the Table 1. Screening the Optimized Reaction Conditionsa

entry

additive

solvent

yield (%)

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

− NaOAc Cu(OAc)2 AgOAc Na2CO3 K3PO4 NaOAc NaOAc NaOAc NaOAc NaOAc NaOAc NaOAc

DCE DCE DCE DCE DCE DCE TFE THF Toluene MeCN DCM DCE DCE

28 86 33 41 8 11 18 21 trace trace 19 49,b (85),c (78),d (69)e trace,f (7),g (0),h (73)i

a

Reaction conditions: 1a (0.2 mmol), 2a (0.3 mmol, 1.5 equiv), [Cp*RhCl2]2 (5 mol %), AgSbF6 (20 mol %), additive (2 equiv), and solvent (2 mL) at 100 °C under N2 for 6 h. b80 °C. c120 °C. d130 °C. e NaOAc (1 equiv). f Using [Ru(p-cymene)Cl 2 ] 2 instead of [Cp*RhCl2]2. gUsing Cp*Co(CO)I2 instead of [Cp*RhCl2]2. hUsing Pd(OAc)2 instead of [Cp*RhCl2]2. iUnder air.

a Reaction conditions: 1 (0.2 mmol), 2 (0.3 mmol), [Cp*RhCl2]2 (5 mol %), AgSbF6 (20 mol %), NaOAc (0.4 mmol) in DCE (2 mL) at 100 °C under N2 for 6 h.

reaction with [Cp*RhCl2]2 as the catalyst and AgSbF6 as the activator and successfully afforded the chalcone-based 3arylated succinimide 3aa in 28% yield (entry 1, Table 1). This first attempt was conducted without the addition of additives, oxidants, or acids. Next, the addition of 2 equiv of NaOAc as additive sharply increased the yield to 86% (entry 2, Table 1). While other acetates, Cu(OAc)2 and AgOAc, did not give positive results (entries 3 and 4, Table 1). Bases, such as Na2CO3 and K3PO4, resulted in very low conversion of the substrate (entries 5 and 6, Table 1). We then checked the solvent effect by using TFE, THF, toluene, acetonitrile, and DCM as the solvent, and they were all inferior to DCE or even restrained the transformation (entries 7−11, Table 1). The yield dropped obviously at lower temperature, while elevated temperatures did not lead to higher yields (entry 12, Table 1). If we switched the catalyst into [Ru(p-cymene)Cl2]2, Cp*Co(CO)I2, or Pd(OAc)2, the reaction did not occur, or only trace amounts of 3aa could be detected (entry 13, Table 1).

adjacent to carbonyl of chalcones (Ar1) have little influence on the efficiency of this hydroarylation, generating corresponding products in good yields (3aa−3ka, 86%−56%). Electrondonating groups, such as methyl and methoxy, or electronwithdrawing groups, such as halo, trifluoromethyl, and methoxycarbonyl, were all well tolerated. Specially, iodo remains innocent under this Rh-catalyzed condition to produce 3ha in 57% yield. meta-Substituted substrate 1f gave the products 3fa in moderate yield and excellent regioselectivity. Besides, heteroarene, such as thiophenyl and pyrrolyl, could also undergo this enone carbonyl directed hydroarylation to generate 3ia and 3ja in 85% and 76% yields, respectively. Moreover, maleimides with different protecting groups, such as ethyl, tert-butyl, and cyclohexyl, all reacted smoothly to give the corresponding 3-arylated succinimides in good yields (3ab−3ad). When N,N′-1,3-phenylene bismaleimide (2e) was 12087

DOI: 10.1021/acs.joc.8b02059 J. Org. Chem. 2018, 83, 12086−12093

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The Journal of Organic Chemistry Chart 2. Substrates Scope of Chalconesa

Scheme 2. Selective Reduction Reaction of 3aa

Scheme 3. Control Experiments for Mechanism Investigation

the case of (E)-prop-1-ene-1,3-diyldibenzene (6) (eq (b), Scheme 3). These results indicated that it is the carbonyl group rather than the olefin moiety that is acting as the directing group in the reaction. Notably, increased yield was observed in the case of chalcone compared with 1,3-diphenylpropan-1-one 5 (86% yield of 3aa vs 63% yield of 6) which indicates that the double bond also played promoting roles. In addition, no reaction occurred between (E)-4-phenylbut-3-en-2-one (7) and 2a (eq (c), Scheme 3). This result further confirmed the site-selective C−H activation occurred at the ortho-C−H bond of arene rather than at the β-H of the enone carbonyl. Next, the H/D exchange experiment was conducted and led to deuterium incorporation at the ortho-positions of chalocone 1a, which indicated that the C−H activation step was reversible (eq (a), Scheme 4). An intermolecular kinetic isotope effect (KIE) of kH/kD = 1.3 suggested that the arene C−H bond cleavage might not be involved in the ratedetermining step (eq (b), Scheme 4). A tentative mechanism is depicted in Scheme 5 based on the mechanism study results and literature reports.10−12 First, the reaction is initiated by the formation of active Rh(III) species

a

Reaction conditions: 1 (0.2 mmol), 2a (0.3 mmol), [Cp*RhCl2]2 (5 mol %), AgSbF6 (20 mol %), NaOAc (0.4 mmol) in DCE (2 mL), at 100 °C, under N2 for 6 h.

utilized in place of 2a, monohydroarylated product 3ae was obtained albeit in a lower yield. Chalcone derivatives with different substituents on aryls adjacent to alkenyl (Ar2) were next tested by reacting with Nmethylmaleimide 2a under standard conditions (Chart 2). Similarly, substrates with electro-donating or -withdrawing groups, such as alkyl, halo, 2-naphthyl, and methoxycarbonyl, all smoothly reacted with maleimide and successfully afforded the desired products in good to moderate yields (3la−3ua). Notably, strong electron-withdrawing groups, such as nitro, resulted in lower yield of 3ta (40% yield). Good yields could also be obtained using chalcone substrates with heteroarenes, like thiophenyl, pyrrolyl, and furanyl (3va−3za, up to 82%). Moreover, selective reductive of the CC bond in product 3aa catalyzed by Pd/C and NaBH4 was achieved, leading to the corresponding product 4 in 53% yield (Scheme 2).15 To gain insights into the reaction mechanism, control experiments were performed (Scheme 3). First, 1,3-diphenylpropan-1-one (5) and (E)-prop-1-ene-1,3-diyldibenzene (6) were utilized as substrate under standard conditions (eqs a and b, Scheme 3). Product 4 was isolated in 63% yield in the former case (eq (a), Scheme 3), while no reaction occurred in

Scheme 4. Experiments on Kinetic Isotope Effect

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DOI: 10.1021/acs.joc.8b02059 J. Org. Chem. 2018, 83, 12086−12093

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The Journal of Organic Chemistry

pressure, and the residue was purified by flash column chromatography on silica gel to give the product. 3-(2-Cinnamoylphenyl)-1-methylpyrrolidine-2,5-dione (3aa). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 3/1) gave a brown liquid (54.8 mg, 86%). Rf = 0.32 (Silica gel, petroleum/ethyl acetate = 3:1). 1H NMR (CDCl3, 400 MHz): δ 7.75 (dd, J = 7.6, 0.8 Hz, 1H), 7.64−7.60 (m, 3H), 7.56−7.52 (m, 1H), 7.48−7.39 (m, 4H), 7.28−7.24 (m, 2H), 4.38−4.34 (m, 1H), 3.29− 3.22 (m, 1H), 3.09 (s, 3H), 2.88−2.82 (m, 1H). 13C{1H} NMR (CDCl3, 100 MHz): δ 194.8, 178.4, 176.5, 146.7, 138.2, 137.1, 134.5, 132.1, 131.1, 130.6, 129.9, 129.1, 128.7, 127.9, 125.3, 45.3, 38.4, 25.2. HRMS (ESI) m/z calcd for C20H17NNaO3 (M + Na)+ 342.1101, found 342.1103. 3-(2-Cinnamoyl-5-methylphenyl)-1-methylpyrrolidine-2,5-dione (3ba). Flash column chromatography on silica gel (petroleum ether/ ethyl acetate 3/1) gave a brown liquid (51.9 mg, 78%). Rf = 0.31 (Silica gel, petroleum/ethyl acetate = 3:1). 1H NMR (CDCl3, 400 MHz): δ 7.69 (d, J = 7.9 Hz, 1H), 7.63−7.59 (m, 3H), 7.42−7.40 (m, 3H), 7.30−7.24 (m, 2H), 7.07 (s, 1H), 4.36−4.32 (m, 1H), 3.27− 3.20 (m, 1H), 3.10 (s, 3H), 2.84−2.78 (m, 1H), 2.42 (s, 3H). 13 C{1H} NMR (CDCl3, 100 MHz): δ 194.2, 178.5, 176.6, 146.1, 142.9, 137.3, 135.2, 134.7, 131.7, 130.9, 130.4, 129.1, 128.7, 128.6, 125.1, 45.4, 38.4, 25.2, 21.6. HRMS (ESI) m/z calcd for C21H19NNaO3 (M + Na)+ 356.1257, found 356.1261. 3-(2-Cinnamoyl-5-methoxyphenyl)-1-methylpyrrolidine-2,5dione (3ca). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 2/1) gave a brown solid (57.9 mg, 83%). Mp 79− 81 °C. Rf = 0.36 (Silica gel, petroleum/ethyl acetate = 2:1). 1H NMR (CDCl3, 400 MHz): δ 7.83 (d, J = 8.6 Hz, 1H), 7.63−7.58 (m, 3H), 7.42−7.40 (m, 3H), 7.31 (d, J = 15.8 Hz), 6.92 (dd, J = 8.6, 2.4 Hz, 1H), 6.79 (d, J = 2.4 Hz, 1H), 4.38−4.34 (m, 1H), 3.87 (s, 3H), 3.26−3.19 (m, 1H), 3.10 (s, 3H), 2.84−2.78 (m, 1H). 13C{1H} NMR (CDCl3, 100 MHz): δ 194.2, 178.5, 176.6, 146.1, 142.9, 137.3, 135.2, 134.7, 131.7, 130.9, 130.4, 129.1, 128.7, 128.6, 125.1, 45.4, 38.4, 25.2, 21.6. HRMS (ESI) m/z calcd for C21H19NNaO4 (M + Na)+ 372.1206, found 372.1201. 3-(2-Cinnamoyl-5-(trifluoromethyl)phenyl)-1-methylpyrrolidine2,5-dione (3da). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 3/1) gave a brown liquid (56.5 mg, 73%). Rf = 0.48 (Silica gel, petroleum/ethyl acetate = 3:1). 1H NMR (CDCl3, 400 MHz): δ 7.81 (d, J = 8.0 Hz, 1H), 7.72 (d, J = 8.0 Hz, 1H), 7.62−7.58 (m, 3H), 7.54 (s, 1H), 7.46−7.42 (m, 3H), 7.20 (d, J = 16.0 Hz, 1H), 4.38−4.34 (m, 1H), 3.29−3.22 (m, 1H), 3.08 (s, 3H), 2.91−2.85 (m, 1H). 13C{1H} NMR (CDCl3, 75 MHz): δ 194.2, 177.3, 175.6, 147.9, 141.5, 137.5, 134.0, 133.3 (q, JC−F = 32.8 Hz), 131.3, 129.8, 129.1, 128.8, 127.3 (q, JC−F = 3.6 Hz), 124.8 (q, JC−F = 3.8 Hz), 124.7, 123.3 (q, JC−F = 271.2 Hz), 44.9, 37.9, 25.1. HRMS (ESI) m/z calcd for C21H16F3NNaO3 (M + Na)+ 410.0974, found 410.0965. 3-(2-Cinnamoyl-5-fluorophenyl)-1-methylpyrrolidine-2,5-dione (3ea). Flash column chromatography on silica gel (petroleum ether/ ethyl acetate 3/1) gave a brown liquid (53.9 mg, 80%). Rf = 0.38 (Silica gel, petroleum/ethyl acetate = 3:1). 1H NMR (CDCl3, 400 MHz): δ 7.81−7.77 (m, 1H), 7.63−7.59 (m, 3H), 7.43−7.41 (m, 3H), 7.24 (d, J = 15.9 Hz), 7.15−7.11 (m, 1H), 7.01−6.98 (m, 1H), 4.38−4.34 (m, 1H), 3.28−3.21 (m, 1H), 3.08 (s, 3H), 2.85−2.78 (m, 1H). 13C{1H} NMR (CDCl3, 100 MHz): δ 193.3, 177.7, 176.1, 164.3 (d, JC−F = 252.7 Hz), 146.7, 140.3 (d, JC−F = 8.0 Hz), 134.4, 134.3, 132.4 (d, JC−F = 9.2 Hz), 131.1, 129.2, 128.8, 124.8, 118.1 (d, JC−F = 22.3 Hz), 114.8 (d, JC−F = 20.9 Hz), 45.2, 38.1, 25.2. HRMS (ESI) m/ z calcd for C20H16FNNaO3 (M + Na)+ 360.1006, found 360.1011. 3-(4-Chloro-2-cinnamoylphenyl)-1-methylpyrrolidine-2,5-dione (3fa). Flash column chromatography on silica gel (petroleum ether/ ethyl acetate 3/1) gave a brown liquid (46.6 mg, 66%). Rf = 0.32 (Silica gel, petroleum/ethyl acetate = 3:1). 1H NMR (CDCl3, 300 MHz): δ 7.69 (d, J = 2.2 Hz, 1H), 7.67−7.61 (m, 3H), 7.52−7.40 (m, 4H), 7.24 (s, 1H), 7.19 (d, J = 6.8 Hz, 1H), 4.33−4.28 (m, 1H), 3.29−3.19 (m, 1H), 3.08 (s, 3H), 2.85−2.77 (m, 1H). 13C{1H} NMR (CDCl3, 75 MHz): δ 193.4, 177.8, 175.9, 147.4, 139.8, 135.2, 134.2, 133.8, 131.8, 131.7, 129.5, 129.1, 128.8, 124.5, 44.5, 38.1, 25.1.

Scheme 5. Proposed Mechanism

A under the assistance of AgSbF6 and NaOAc. Then the following ortho-C−H metalation of A with chalcone 1a provides a rhodacycle B together with the elimination of HOAc. Subsequently, migratory insertion of alkene 2a into rhodacycle B leads to a seven-membered rhodacycle intermediate C. Finally, proto demetalation of intermediate C gives the product 3aa and regenerates the active catalyst species A. Intermediate C cannot undergo β-hydride elimination due to the unavailability of a syn-periplanar βhydrogen atom. As a result, the 1,4-addition products were exclusively obtained without Heck-type products detected.

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CONCLUSIONS In conclusion, we have developed a rhodium(III)-catalyzed direct hydroarylation of malemides through enone carbonyl directed ortho-C−H activation with chalcones. Enone carbonyl was first used as a directing group in the hydroarylation of malemides leading to a series of compounds bearing both chalcone and succinimide scaffolds in good to moderate yields. Neither excess amounts of external oxidants nor excess amounts of acids were needed in our procedure. This protocol also created opportunities for enriching the libraries of diversified highly functionalized succinimides and chalcones for biological studies.

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EXPERIMENTAL SECTION

General Information. All chemicals were used as received without further purification unless stated otherwise. NMR spectra were recorded at ambient temperature on a 300 or 400 M NMR spectrometer. Chemical shifts (δ) are given in ppm relative to TMS, and the coupling constants J are given in Hz. HRMS were recorded on a TOF LC/MS equipped with electrospray ionization (ESI) probe operating in positive or negative ion mode. Experimental General Procedure. Under N2, the mixture of 1 (0.2 mmol), 2 (0.3 mmol), [Cp*RhCl2]2 (5 mol %, 6.2 mg), AgSbF6 (20 mol %, 13.6 mg), and NaOAc (0.4 mmol, 32.8 mg) in DCE (2 mL) were added into the tube and sealed. The mixture was stirred at 100 °C for 6 h. Then, the solvent was evaporated under reduced 12089

DOI: 10.1021/acs.joc.8b02059 J. Org. Chem. 2018, 83, 12086−12093

Article

The Journal of Organic Chemistry HRMS (ESI) m/z calcd for C20H16ClNNaO3 (M + Na)+ 376.0711, found 376.0715. 3-(5-Bromo-2-cinnamoylphenyl)-1-methylpyrrolidine-2,5-dione (3ga). Flash column chromatography on silica gel (petroleum ether/ ethyl acetate 3/1) gave a brown liquid (54.0 mg, 68%). Rf = 0.39 (Silica gel, petroleum/ethyl acetate = 3:1). 1H NMR (CDCl3, 400 MHz): δ 7.63−7.57 (m, 5H), 7.44−7.41 (m, 4H), 7.21 (d, J = 16.0 Hz, 1H), 4.32−4.28 (m, 1H), 3.27−3.20 (m, 1H), 3.08 (s, 3H), 2.86−2.80 (m, 1H). 13C{1H} NMR (CDCl3, 100 MHz): δ 193.8, 177.7, 176.0, 147.2, 139.0, 136.9, 134.3, 133.8, 131.3, 131.1, 129.2, 128.8, 126.5, 124.8, 44.9, 38.1, 25.3. HRMS (ESI) m/z calcd for C20H16BrNNaO3 (M + Na)+ 420.0206, found 420.0215. 3-(2-Cinnamoyl-5-iodophenyl)-1-methylpyrrolidine-2,5-dione (3ha). Flash column chromatography on silica gel (petroleum ether/ ethyl acetate 3/1) gave a brown liquid (50.7 mg, 57%). Rf = 0.41 (Silica gel, petroleum/ethyl acetate = 3:1). 1H NMR (CDCl3, 300 MHz): δ 7.81−7.78 (m, 1H), 7.63−7.57 (m, 4H), 7.46−7.41 (m, 4H), 7.18 (d, J = 16.0 Hz, 1H), 4.28−4.22 (m, 1H), 3.26−3.17 (m, 1H), 3.07 (s, 3H), 2.86−2.78 (m, 1H). 13C{1H} NMR (CDCl3, 75 MHz): δ 193.9, 177.5, 175.9, 147.0, 139.6, 138.7, 137.5, 134.2, 131.1, 130.9, 129.1, 128.7, 124.6, 98.8, 44.7, 37.9, 25.1. HRMS (ESI) m/z calcd for C20H16INNaO3 (M + Na)+ 468.0067, found 468.0081. 3-(2-Cinnamoylthiophen-3-yl)-1-methylpyrrolidine-2,5-dione (3ia). Flash column chromatography on silica gel (petroleum ether/ ethyl acetate 3/1) gave a brown liquid (55.2 mg, 85%). Rf = 0.26 (Silica gel, petroleum/ethyl acetate = 3:1). 1H NMR (CDCl3, 400 MHz): δ 7.78 (d, J = 15.4 Hz, 1H), 7.62−7.59 (m, 3H), 7.42−7.40 (m, 3H), 7.30 (d, J = 15.4 Hz, 1H), 7.09 (d, J = 4.9 Hz, 1H), 4.71− 4.67 (m, 1H), 3.26−3.19 (m, 1H), 3.13 (s, 3H), 2.75−2.69 (m, 1H). 13 C{1H} NMR (CDCl3, 100 MHz): δ 182.2, 177.5, 176.5, 145.2, 143.5, 137.1, 134.5, 131.8, 130.9, 130.8, 129.1, 128.7, 123.2, 42.1, 36.9, 25.3. HRMS (ESI) m/z calcd for C18H15NNaO3S (M + Na)+ 348.0665, found 348.0668. (E)-3-(2-Cinnamoyl-1-methyl-1H-pyrrol-3-yl)-1-methylpyrrolidine-2,5-dione (3ja). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 2/1) gave a brown liquid (48.9 mg, 76%). Rf = 0.44 (Silica gel, petroleum/ethyl acetate = 2:1). 1H NMR (CDCl3, 300 MHz): δ 7.64 (d, J = 15.8 Hz, 1H), 7.59−7.56 (m, 2H), 7.45 (d, J = 15.8 Hz, 1H), 7.39−7.37 (m, 3H), 6.76 (d, J = 2.7 Hz, 1H), 5.96 (d, J = 2.7 Hz, 1H), 4.42−4.38 (m, 1H), 3.83 (s, 3H), 3.16−3.07 (m, 1H), 3.03 (s, 3H), 2.77−2.69 (m, 1H). 13C{1H} NMR (CDCl3, 75 MHz): δ 183.1, 178.1, 176.4, 143.7, 134.7, 131.2, 130.5, 129.3, 129.0, 128.4, 127.1, 126.3, 107.1, 39.2, 37.9, 37.4, 25.2. HRMS (ESI) m/z calcd for C19H18N2NaO3 (M + Na)+ 345.1210, found 345.1215. Methyl 4-Cinnamoyl-3-(1-methyl-2,5-dioxopyrrolidin-3-yl)benzoate (3ka). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 2/1) gave a brown liquid (42.2 mg, 56%). Rf = 0.41 (Silica gel, petroleum/ethyl acetate = 2:1). 1H NMR (CDCl3, 400 MHz): δ 8.09 (d, J = 8.0 Hz, 1H), 7.93 (d, J = 1.2 Hz, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.62−7.58 (m, 3H), 7.43−7.39 (m, 3H), 7.21 (d, J = 16.0 Hz, 1H), 4.39−4.35 (m, 1H), 3.96 (s, 3H), 3.29−3.22 (m, 1H), 3.08 (s, 3H), 2.89−2.84 (m, 1H). 13C{1H} NMR (CDCl3, 75 MHz): δ 194.6, 177.7, 175.9, 165.7, 147.6, 142.2, 136.9, 134.1, 132.8, 131.2, 129.4, 129.1, 128.9, 128.8, 124.9, 52.6, 44.7, 38.0, 25.2. HRMS (ESI) m/z calcd for C22H19NNaO5 (M + Na)+ 400.1155, found 400.1161. 3-(2-Cinnamoylphenyl)-1-ethylpyrrolidine-2,5-dione (3ab). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 3/1) gave a brown liquid (50.6 mg, 76%). Rf = 0.43 (Silica gel, petroleum/ethyl acetate = 3:1). 1H NMR (CDCl3, 400 MHz): δ 7.73 (d, J = 7.6 Hz, 1H), 7.63−7.58 (m, 3H), 7.54−7.50 (m, 1H), 7.46− 7.40 (m, 4H), 7.28−7.24 (m, 2H), 4.33−4.29 (m, 1H), 3.64 (q, J = 7.2 Hz, 2H), 3.25−3.18 (m, 1H), 2.89−2.83 (m, 1H), 1.25 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (CDCl3, 100 MHz): δ 194.7, 178.1, 176.2, 146.6, 138.3, 137.2, 134.6, 132.1, 131.0, 130.6, 129.8, 129.1, 128.8, 127.9, 125.3, 45.2, 38.5, 34.2, 13.2. HRMS (ESI) m/z calcd for C21H19NNaO3 (M + Na)+ 356.1257, found 356.1261. 1-(tert-Butyl)-3-(2-cinnamoylphenyl)pyrrolidine-2,5-dione (3ac). Flash column chromatography on silica gel (petroleum ether/ethyl

acetate 3/1) gave a brown liquid (51.3 mg, 71%). Rf = 0.56 (Silica gel, petroleum/ethyl acetate = 3:1). 1H NMR (CDCl3, 400 MHz): δ 7.72 (d, J = 7.7 Hz, 1H), 7.64−7.59 (m, 3H), 7.54−7.50 (m, 1H), 7.45− 7.41 (m, 4H), 7.28−7.24 (m, 2H), 4.21−4.17 (m, 1H), 3.14−3.07 (m, 1H), 2.83−2.77 (m, 1H), 1.64 (s, 9H). 13C{1H} NMR (CDCl3, 100 MHz): δ 194.8, 179.3, 177.3, 146.5, 138.4, 137.9, 134.7, 131.9, 130.9, 130.6, 129.7, 129.1, 128.7, 127.6, 125.4, 58.8, 45.2, 38.8, 28.6. HRMS (ESI) m/z calcd for C23H23NNaO3 (M + Na)+ 384.1570, found 384.1577. 3-(2-Cinnamoylphenyl)-1-cyclohexylpyrrolidine-2,5-dione (3ad). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 3/1) gave a brown liquid (61.9 mg, 80%). Rf = 0.47 (Silica gel, petroleum/ethyl acetate = 3:1). 1H NMR (CDCl3, 300 MHz): δ 7.64 (m, 1H), 7.54−7.48 (m, 3H), 7.45−7.39 (m, 1H), 7.37−7.32 (m, 4H), 7.28−7.13 (m, 2H), 4.19−4.14 (m, 1H), 4.01−3.91 (m, 1H), 3.12−3.03 (m, 1H), 2.76−2.68 (m, 1H), 2.19−2.03 (m, 2H), 1.72− 1.54 (m, 4H), 1.32−1.06 (m, 4H). 13C{1H} NMR (CDCl3, 100 MHz): δ 194.7, 178.3, 176.5, 146.6, 138.4, 137.5, 134.6, 131.9, 131.0, 130.5, 129.7, 129.1, 128.7, 127.7, 125.4, 52.1, 44.8, 38.3, 28.99, 28.95, 26.1, 26.0, 25.2. HRMS (ESI) m/z calcd for C25H25NNaO3 (M + Na)+ 410.1727, found 410.1722. (E)-1-(3-(3-(2-Cinnamoylphenyl)-2,5-dioxopyrrolidin-1-yl)phenyl)-1H-pyrrole-2,5-dione (3ae). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 1/1) gave a brown liquid (31.4 mg, 33%). Rf = 0.44 (Silica gel, petroleum/ethyl acetate = 1:1). 1 H NMR (CDCl3, 400 MHz): δ 7.83 (dd, J = 7.6, 1.1 Hz, 1H), 7.71 (d, J = 15.9 Hz, 1H), 7.64−7.48 (m, 12H), 7.33 (d, J = 15.9 Hz, 1H), 4.44−4.40 (m, 1H), 3.39−3.33 (m, 1H), 3.12−3.06 (m, 1H). 13 C{1H} NMR (CDCl3, 75 MHz): δ 194.4, 176.7, 174.5, 168.9, 146.7, 137.5, 136.8, 134.5, 134.2, 132.9, 132.2, 132.0, 130.9, 130.1, 129.5, 128.9, 128.7, 128.1, 125.8, 125.3, 124.6, 123.8, 46.1, 38.1. HRMS (ESI) m/z calcd for C29H20N2NaO5 (M + Na)+ 499.1264, found 499.1253. (E)-1-Methyl-3-(2-(3-(p-tolyl)acryloyl)phenyl)pyrrolidine-2,5dione (3la). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 3/1) gave a brown liquid (53.9 mg, 81%). Rf = 0.41 (Silica gel, petroleum/ethyl acetate = 3:1). 1H NMR (CDCl3, 400 MHz): δ 7.73 (d, J = 7.6 Hz, 1H), 7.59 (d, J = 15.9 Hz, 1H), 7.54−7.49 (m, 3H), 7.44 (t, J = 7.6 Hz, 1H), 7.28−7.19 (m, 4H), 4.36−4.32 (m, 1H), 3.27−3.20 (m, 1H), 3.08 (s, 3H), 2.85−2.79 (m, 1H), 2.39 (s, 3H). 13C{1H} NMR (CDCl3, 100 MHz): δ 194.9, 178.4, 176.5, 146.9, 141.7, 138.4, 136.9, 131.9, 131.8, 130.5, 129.9, 129.8, 128.8, 127.9, 124.3, 45.2, 38.4, 25.2, 21.7. HRMS (ESI) m/z calcd for C21H19NNaO3 (M + Na)+ 356.1257, found 356.1261. (E)-1-Methyl-3-(2-(3-(m-tolyl)acryloyl)phenyl)pyrrolidine-2,5dione (3ma). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 3/1) gave a brown liquid (52.6 mg, 79%). Rf = 0.33 (Silica gel, petroleum/ethyl acetate = 3:1). 1H NMR (CDCl3, 400 MHz): δ 7.74 (d, J = 7.6 Hz, 1H), 7.59 (d, J = 15.9 Hz, 1H), 7.53 (t, J = 7.5 Hz, 1H), 7.47−7.40 (m, 3H), 7.33−7.22 (m, 4H), 4.37− 4.33 (m, 1H), 3.29−3.22 (m, 1H), 3.09 (s, 3H), 2.87−2.80 (m, 1H), 2.39 (s, 3H). 13C{1H} NMR (CDCl3, 100 MHz): δ 194.9, 178.4, 176.5, 146.9, 138.8, 138.3, 137.0, 134.5, 132.0, 131.9, 130.5, 129.8, 129.4, 129.0, 127.9, 125.9, 125.1, 45.2, 38.4, 25.2, 21.5. HRMS (ESI) m/z calcd for C21H19NNaO3 (M + Na)+ 356.1257, found 356.1261. (E)-3-(2-(3-(4-(tert-Butyl)phenyl)acryloyl)phenyl)-1-methylpyrrolidine-2,5-dione (3na). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 3/1) gave a brown liquid (63.0 mg, 84%). Rf = 0.35 (Silica gel, petroleum/ethyl acetate = 3:1). 1H NMR (CDCl3, 400 MHz): δ 7.72 (d, J = 7.5 Hz, 1H), 7.60 (d, J = 15.9 Hz, 1H), 7.56−7.50 (m, 3H), 7.46−7.42 (m, 3H), 7.27 (d, J = 7.5 Hz, 1H), 7.23 (d, J = 15.9 Hz, 1H), 4.37−4.33 (m, 1H), 3.28−3.21 (m, 1H), 3.09 (s, 3H), 2.86−2.80 (m, 1H), 1.35 (s, 9H). 13C{1H} NMR (CDCl3, 100 MHz): δ 195.0, 178.4, 176.5, 154.8, 146.9, 138.5, 137.0, 131.9, 131.8, 130.5, 129.8, 128.7, 127.9, 126.1, 124.6, 45.2, 38.4, 35.1, 31.3, 25.2. HRMS (ESI) m/z calcd for C24H25NNaO3 (M + Na)+ 398.1727, found 398.1718. (E)-3-(2-(3-(4-Fluorophenyl)acryloyl)phenyl)-1-methylpyrrolidine-2,5-dione (3oa). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 3/1) gave a brown liquid (49.2 mg, 12090

DOI: 10.1021/acs.joc.8b02059 J. Org. Chem. 2018, 83, 12086−12093

Article

The Journal of Organic Chemistry 73%). Rf = 0.32 (Silica gel, petroleum/ethyl acetate = 3:1). 1H NMR (CDCl3, 400 MHz): δ 7.73 (d, J = 7.6 Hz, 1H), 7.61−7.50 (m, 4H), 7.46−7.42 (m, 1H), 7.27 (d, J = 7.2 Hz, 1H), 7.18 (d, J = 15.9 Hz, 1H), 7.12−7.07 (m, 2H), 4.36−4.32 (m, 1H), 3.28−3.20 (m, 1H), 3.08 (s, 3H), 2.86−2.80 (m, 1H). 13C{1H} NMR (CDCl3, 100 MHz): δ 194.6, 178.4, 176.5, 164.4 (d, JC−F = 250.9 Hz), 145.3, 138.2, 137.0, 132.1, 130.8 (d, JC−F = 3.4 Hz), 130.8, 130.6 (d, JC−F = 3.4 Hz), 129.8, 127.9, 124.9 (d, JC−F = 2.1 Hz), 116.3 (d, JC−F = 21.8 Hz), 45.2, 38.4, 25.2. HRMS (ESI) m/z calcd for C20H16FNNaO3 (M + Na)+ 360.1006, found 360.1009. (E)-3-(2-(3-(4-Chlorophenyl)acryloyl)phenyl)-1-methylpyrrolidine-2,5-dione (3pa). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 3/1) gave a coloress liquid (53.6 mg, 76%). Rf = 0.36 (Silica gel, petroleum/ethyl acetate = 3:1). 1H NMR (CDCl3, 400 MHz): δ 7.73 (d, J = 7.6 Hz, 1H), 7.57−7.51 (m, 4H), 7.44 (t, J = 7.5 Hz, 1H), 7.37 (d, J = 8.4 Hz, 2H), 7.27 (d, J = 7.2 Hz, 1H), 7.22 (d, J = 15.9 Hz, 1H), 4.36−4.32 (m, 1H), 3.27−3.20 (m, 1H), 3.07 (s, 3H), 2.86−2.79 (m, 1H). 13C{1H} NMR (CDCl3, 100 MHz): δ 194.5, 178.4, 176.5, 145.1, 138.0, 137.0, 136.9, 133.1, 132.2, 130.7, 129.9, 129.8, 129.4, 127.9, 125.6, 45.3, 38.3, 25.2. HRMS (ESI) m/z calcd for C20H16ClNNaO3 (M + Na)+ 376.0711, found 376.0716. (E)-3-(2-(3-(4-Bromophenyl)acryloyl)phenyl)-1-methylpyrrolidine-2,5-dione (3qa). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 3/1) gave a brown liquid (56.4 mg, 71%). Rf = 0.37 (Silica gel, petroleum/ethyl acetate = 3:1). 1H NMR (CDCl3, 400 MHz): δ 7.73 (d, J = 7.6 Hz, 1H), 7.55−7.51 (m, 4H), 7.46−7.42 (m, 3H), 7.28−7.22 (m, 2H), 4.36−4.32 (m, 1H), 3.27− 3.20 (m, 1H), 3.07 (s, 3H), 2.86−2.79 (m, 1H). 13C{1H} NMR (CDCl3, 100 MHz): δ 194.4, 178.3, 176.4, 145.1, 138.0, 137.1, 133.5, 132.4, 132.3, 130.7, 130.1, 129.9, 127.9, 125.7, 125.3, 45.3, 38.3, 25.2. HRMS (ESI) m/z calcd for C20H16BrNNaO3 (M + Na)+ 420.0206, found 420.0221. (E)-3-(2-(3-(3-Bromophenyl)acryloyl)phenyl)-1-methylpyrrolidine-2,5-dione (3ra). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 3/1) gave a brown liquid (54.0 mg, 68%). Rf = 0.35 (Silica gel, petroleum/ethyl acetate = 3:1). 1H NMR (CDCl3, 400 MHz): δ 7.75−7.73 (m, 2H), 7.56−7.44 (m, 5H), 7.31−7.23 (m, 3H), 4.37−4.33 (m, 1H), 3.28−3.21 (m, 1H), 3.08 (s, 3H), 2.87−2.80 (m, 1H). 13C{1H} NMR (CDCl3, 100 MHz): δ 194.3, 178.3, 176.4, 144.7, 137.8, 137.1, 136.7, 133.7, 132.3, 131.2, 130.8, 130.6, 129.9, 127.9, 127.4, 126.3, 123.2, 45.3, 38.3, 25.2. HRMS (ESI) m/z calcd for C20H16BrNNaO3 (M + Na)+ 420.0206, found 420.0221. (E)-1-Methyl-3-(2-(3-(naphthalen-2-yl)acryloyl)phenyl)pyrrolidine-2,5-dione (3sa). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 3/1) gave a brown liquid (41.3 mg, 56%). Rf = 0.34 (Silica gel, petroleum/ethyl acetate = 3:1). 1H NMR (CDCl3, 300 MHz): δ 8.01 (s, 1H), 7.89−7.74 (m, 6H), 7.58−7.45 (m, 4H), 7.37 (d, J = 15.9 Hz, 1H), 7.31−7.28 (m, 1H), 4.41−4.36 (m, 1H), 3.32−3.23 (m, 1H), 3.11 (s, 3H), 2.91−2.83 (m, 1H). 13 C{1H} NMR (CDCl3, 75 MHz): δ 194.7, 178.3, 176.4, 146.7, 138.2, 136.9, 134.5, 133.3, 131.9, 131.1, 130.4, 129.8, 128.8, 128.7, 127.85, 127.82, 127.6, 126.8, 125.3, 123.6, 45.1, 38.3, 25.1. HRMS (ESI) m/z calcd for C24H19NNaO3 (M + Na)+ 392.1257, found 392.1263. (E)-1-Methyl-3-(2-(3-(3-nitrophenyl)acryloyl)phenyl)pyrrolidine2,5-dione (3ta). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 2/1) gave a brown liquid (29.1 mg, 40%). Rf = 0.43 (Silica gel, petroleum/ethyl acetate = 2:1). 1H NMR (CDCl3, 400 MHz): δ 8.46 (d, J = 1.5 Hz, 1H), 8.26 (d, J = 8.2 Hz, 1H), 7.90 (d, J = 7.8 Hz, 1H), 7.79 (d, J = 7.6 Hz, 1H), 7.67−7.55 (m, 3H), 7.49 (t, J = 7.6 Hz, 1H), 7.39 (d, J = 15.9 Hz, 1H), 7.31 (d, J = 7.6 Hz, 1H), 4.39−4.35 (m, 1H), 3.29−3.22 (m, 1H), 3.09 (s, 3H), 2.89−2.83 (m, 1H). 13C{1H} NMR (CDCl3, 75 MHz): δ 193.7, 177.2, 176.2, 148.7, 143.1, 137.3, 137.1, 136.2, 134.2, 132.5, 130.9, 130.1, 129.9, 127.9, 127.5, 124.9, 122.7, 42.2, 39.1, 25.1. HRMS (ESI) m/z calcd for C20H16N2NaO5 (M + Na)+ 387.0951, found 387.0958. (E)-Methyl 4-(3-(2-(1-methyl-2,5-dioxopyrrolidin-3-yl)phenyl)-3oxoprop-1-enyl)benzoate (3ua). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 2/1) gave a brown liquid

(51.3 mg, 68%). Rf = 0.43 (Silica gel, petroleum/ethyl acetate = 2:1). 1 H NMR (CDCl3, 400 MHz): δ 8.06 (d, J = 8.4 Hz, 1H), 7.76 (dd, J = 7.6, 1.3 Hz, 1H), 7.65 (d, J = 8.4 Hz, 2H), 7.61 (d, J = 16.0 Hz, 1H), 7.56−7.52 (m, 1H), 7.48−7.43 (m, 1H), 7.33 (d, J = 15.9 Hz, 1H), 7.29−7.27 (m, 1H), 4.37−4.33 (m, 1H), 3.93 (s, 3H), 3.28− 3.21 (m, 1H), 3.07 (s, 3H), 2.86−2.80 (m, 1H). 13C{1H} NMR (CDCl3, 100 MHz): δ 194.3, 178.3, 176.4, 166.5, 144.9, 138.8, 137.8, 137.1, 132.4, 131.9, 130.8, 130.3, 129.9, 128.5, 128.0, 127.1, 52.5, 45.3, 38.3, 25.2. HRMS (ESI) m/z calcd for C22H19NNaO5 (M + Na)+ 400.1155, found 400.1158. (E)-1-Methyl-3-(2-(3-(1-methyl-1H-pyrrol-2-yl)acryloyl)phenyl)pyrrolidine-2,5-dione (3va). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 2/1) gave a brown liquid (34.1 mg, 53%). Rf = 0.46 (Silica gel, petroleum/ethyl acetate = 2:1). 1H NMR (CDCl3, 400 MHz): δ 7.70 (dd, J = 7.6, 1.2 Hz, 1H), 7.59 (d, J = 15.4 Hz, 1H), 7.51−7.41 (m, 2H), 7.24 (d, J = 7.6 Hz, 1H), 7.01 (d, J = 15.4 Hz, 1H), 6.84−6.82 (m, 2H), 6.24−6.22 (m, 1H), 4.37−4.33 (m, 1H), 3.73 (s, 3H), 3.28−3.21 (m, 1H), 3.09 (s, 3H), 2.86−2.80 (m, 1H). 13C{1H} NMR (CDCl3,75 MHz): δ 194.0, 178.4, 176.5, 139.1, 136.6, 133.8, 131.5, 130.1, 129.8, 129.3, 128.6, 127.8, 119.6, 113.5, 110.1, 45.1, 38.4, 34.5, 25.1. HRMS (ESI) m/z calcd for C19H18N2NaO3 (M + Na)+ 345.1210, found 345.1215. (E)-1-Methyl-3-(2-(3-(thiophen-2-yl)acryloyl)phenyl)pyrrolidine2,5-dione (3wa). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 3/1) gave a brown liquid (53.3 mg, 82%). Rf = 0.35 (Silica gel, petroleum/ethyl acetate = 3:1). 1H NMR (CDCl3, 400 MHz): δ 7.74 (d, J = 8.2 Hz, 1H), 7.71 (s, 1H), 7.53− 7.42 (m, 3H), 7.34−7.32 (m, 1H), 7.26 (d, J = 7.6 Hz, 1H), 7.09− 7.02 (m, 2H), 4.35−4.31 (m, 1H), 3.26−3.19 (m, 1H), 3.07 (s, 3H), 2.84−2.78 (m, 1H). 13C{1H} NMR (CDCl3, 100 MHz): δ 194.1, 178.4, 176.5, 140.0, 138.9, 138.1, 136.9, 132.7, 132.1, 130.7, 129.7, 128.6, 127.9, 123.9, 45.3, 38.4, 25.2. HRMS (ESI) m/z calcd for C18H15NNaO3S (M + Na)+ 348.0665, found 348.0668. (E)-3-(2-(3-(Furan-2-yl)acryloyl)phenyl)-1-methylpyrrolidine-2,5dione (3xa). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 3/1) gave a brown liquid (40.8 mg, 66%). Rf = 0.5 (Silica gel, petroleum/ethyl acetate = 2:1). 1H NMR (CDCl3, 400 MHz): δ 7.75 (d, J = 7.6 Hz, 1H), 7.54−7.42 (m, 3H), 7.39 (d, J = 15.5 Hz, 1H), 7.26 (d, J = 7.4 Hz, 1H), 7.16 (d, J = 15.5 Hz, 1H), 6.73 (d, J = 3.4 Hz, 1H), 6.51 (dd, J = 3.2, 1.6 Hz, 1H), 4.36−4.33 (m, 1H), 3.27−3.19 (m, 1H), 3.08 (s, 3H), 2.85−2.79 (m, 1H). 13 C{1H} NMR (CDCl3, 100 MHz): δ 194.0, 178.4, 176.6, 151.3, 145.5, 138.1, 136.9, 132.3, 132.1, 130.8, 129.8, 127.9, 122.4, 117.1, 112.9, 45.4, 38.3, 25.2. HRMS (ESI) m/z calcd for C18H15NNaO4 (M + Na)+ 332.0893, found 332.0889. (E)-1-Methyl-3-(2-(3-(thiophen-2-yl)acryloyl)thiophen-3-yl)pyrrolidine-2,5-dione (3ya). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 3/1) gave a brown solid (47.0 mg, 71%). mp 85−87 °C. Rf = 0.4 (Silica gel, petroleum/ethyl acetate = 2:1). 1H NMR (CDCl3, 400 MHz): δ 7.88 (d, J = 15.0 Hz, 1H), 7.58 (d, J = 4.9 Hz, 1H), 7.44 (d, J = 4.9 Hz, 1H), 7.36 (d, J = 3.5 Hz, 1H), 7.11−7.07 (m, 3H), 4.70−4.66 (m, 1H), 3.25−3.18 (m, 1H), 3.13 (s, 3H), 2.74−2.68 (m, 1H). 13C{1H} NMR (CDCl3, 100 MHz): δ 181.8, 177.5, 176.5, 143.3, 139.9, 137.5, 137.0, 132.6, 131.7, 130.7, 129.5, 128.6, 121.9, 42.1, 36.9, 25.2. HRMS (ESI) m/z calcd for C16H13NNaO3S2 (M + Na)+ 354.0229, found 354.0231. (E)-3-(2-(3-(Furan-2-yl)acryloyl)thiophen-3-yl)-1-methylpyrrolidine-2,5-dione (3za). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 3/1) gave a brown liquid (46.6 mg, 74%). Rf = 0.41 (Silica gel, petroleum/ethyl acetate = 2:1). 1H NMR (CDCl3, 400 MHz): δ 7.58−7.49 (m, 1H), 7.18 (d, J = 15.0 Hz, 1H), 7.07 (d, J = 4.9 Hz, 1H), 6.72 (d, J = 3.3 Hz, 1H), 6.51−6.49 (m, 1H), 4.70−4.66 (m, 1H), 3.24−3.17 (m, 1H), 3.11 (s, 3H), 2.73− 2.67 (m, 1H). 13C{1H} NMR (CDCl3, 100 MHz): δ 181.9, 177.5, 176.6, 151.4, 145.4, 143.2, 137.2, 131.7, 130.8, 130.7, 120.6, 117.1, 112.9, 42.1, 36.9, 25.2. HRMS (ESI) m/z calcd for C16H13NNaO4S (M + Na)+ 338.0457, found 338.0452. 1-Methyl-3-(2-(3-phenylpropanoyl)phenyl)pyrrolidine-2,5-dione (4). Flash column chromatography on silica gel (petroleum ether/ ethyl acetate 2/1) gave a colorless liquid. Rf = 0.53 (Silica gel, 12091

DOI: 10.1021/acs.joc.8b02059 J. Org. Chem. 2018, 83, 12086−12093

Article

The Journal of Organic Chemistry petroleum/ethyl acetate = 2:1). 1H NMR (CDCl3, 400 MHz): δ 7.79 (dd, J = 7.8, 1.2 Hz, 1H), 7.54−7.49 (m, 1H), 7.44−7.40 (m, 1H), 7.33−7.2−0 (m, 6H), 4.34−4.30 (m, 1H), 3.31−3.27 (m, 1H), 3.21− 3.14 (m, 1H), 3.09 (s, 3H), 3.02−3.95 (m, 1H), 2.77−2.70 (m, 1H). 13 C{1H} NMR (CDCl3, 100 MHz): δ 203.1, 178.4, 176.5, 143.0, 136.8, 136.7, 132.7, 131.7, 129.9, 128.7, 128.5, 128.3, 126.3, 46.1, 42.6, 37.9, 30.3, 25.1. HRMS (ESI) m/z calcd for C20H19NNaO3 (M + Na)+ 344.1257, found 344.1259.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.8b02059. Mechanism study, 1H and 13C NMR spectra of compounds 3aa-3za, 3ab-3ae, and 4 (PDF)

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Jin-Tao Yu: 0000-0002-0264-9407 Changduo Pan: 0000-0001-5878-3835 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank the National Natural Science Foundation of China (21602086, 21672028, and 21701060), the Natural Science Foundation for Colleges and Universities of Jiangsu Province (16KJB150002), and Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology (BM2012110) for financial supports.

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REFERENCES

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DOI: 10.1021/acs.joc.8b02059 J. Org. Chem. 2018, 83, 12086−12093

Article

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DOI: 10.1021/acs.joc.8b02059 J. Org. Chem. 2018, 83, 12086−12093