Selective and tunable synthesis of 3-arylsuccinimides and 3-arylmaleimides from arenediazonium tetrafluoroborates and maleimides

Abstract

A highly efficient synthetic strategy for synthesizing 3-arylsuccinimides has been developed from arenediazonium tetrafluoroborates and maleimides in the presence of TiCl₃. The reactions generated 3-arylsuccinimides in satisfactory yields under mild reaction conditions. In addition, 3-arylmaleimides were obtained by the coupling of arenediazonium tetrafluoroborate and maleimides catalyzed by CuCl. This methodology provided the selective and tunable synthesis of two classes of products by simply switching different metal reagents. The methods are simple, efficient and practical.

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Succinimides and related maleimides are an important class of heterocyclic compounds, especially due to the wide range of biological activity that is demonstrated by representative examples of these molecules (Scheme 1).¹ 3-Substituted maleimide and succinimide compounds are also versatile building blocks in organic synthesis. They serve as key precursors in the synthesis of a variety of natural products,² pharmaceuticals³ and functional materials.⁴ Therefore, the development of efficient synthetic methods to access these succinimides and maleimides is attractive for organic chemists.

Scheme 1 Examples of 3-substituted succinimides and maleimides as biological targets.

In view of the synthetic expediency of 3-substitued succinimides and maleimides, many methods have been developed for their synthesis (Scheme 2). Generally, 3-arylsuccinimides can be prepared by the reaction of 3-arylsuccinic acid with urea⁵ or ammonia^1b under 180–200 °C. Iron-catalyzed synthesis of succinimides by carbonylation of different terminal and internal alkynes with ammonia or amines was reported by Driller in 2009. Fe₃(CO)₁₂ catalyzed the carbonylation of 3-hexyne with 20 bar CO in presence of NH₃ to give 3,4-diethylsuccinimide with 84% yield.⁶ Microwave-enhanced rhodium-catalyzed conjugated-addition of arylboronic acids to maleimides provided 3-arylsuccimides with 34–80% yields.⁷ AlCl₃ or AlBr₃-mediated addition of benzene with maleimides was developed by Olah with 34–83% yield using a large excess amount of AlCl₃ or AlBr₃.⁸ However, the above methods have many disadvantages such as low or moderate yield, poor selectivity, complex manipulation and unwanted side products. Most of the reactions usually demand high catalyst loadings, long reaction times, expensive and hazardous reagents, and special reaction conditions to enhance reactivity such as high temperature and microwave irradiation.⁷ Thus, an efficient, economical and environmentally synthetic methodology is highly desirable for this process.

Scheme 2 Synthesis of 3-arylmaleimides and 3-arylsuccinimides ramifications.

Arenediazonium salts have been increasingly used by organic chemists in cross-coupling reactions due to both their wide availability and high reactivity as arylation reagents.⁹ Notably, the superelectrophile properties of arenediazonium salts allows the reaction to proceed under mild conditions (T < 60 °C), without the need of the ligands, and occasionally base. The simple and efficient experimental procedure these reagents enable features many advantages including lower energy, cost, waste, all of which are of interest for the development of sustainable processes. For the synthesis of 3-arylmaleimides, the classical method for the direct C3–H arylation of maleimide is the Meerwein arylation, but this copper-mediated method of maleimide arylation suffers from low or moderate yields.¹⁰ Hence, 3-arylmaleimide derivatives were usually prepared from 3-arylsuccinimide using DDQ and MnO₂ as oxidation agents.¹¹ In our continuing research program directed toward the synthesis of succinimide and related maleimide derivatives,¹² we became intrigued by the idea of using inexpensive Lewis acids to obtain 3-substituted succinimides and maleimides from maleimides and diazonium salts. As an example, TiCl₃ is currently widely used as both a free radical initiator and reductive in organic syntheses.¹³ In light of the important pharmaceutical implications of the unique structural motif of 3-arylsuccinimides and 3-arylmaleimides, herein we report an efficient synthetic strategy toward 3-arylsuccinimides from arenediazonium tetrafluoroborates and maleimides in the presence of TiCl₃. In addition, 3-arylmaleimides were obtained by the coupling of arenediazonium tetrafluoroborates and maleimides catalyzed by CuCl (Scheme 2).

We initiated our studies by examining catalyst usefulness and reaction conditions using maleimide (1) and benzenediazonium tetrafluoroborate (2) as a model system because the product is easy to detect and isolate. First, benzenediazonium tetrafluoroborate was prepared from aniline, fluoroboric acid and sodium nitrite by the classic procedure, because it is more stable than the corresponding chlorides and avoids side reactions induced by halogens. Since, titanium(III) salts served as monoelectronic reducing metal cations in the hemolytic reductive arylation of olefins,^13,14 we used commercial available titanium(III) chloride, which is 15% in 2 N HCl solution. The maleimides are unstable in the presence of strong acids and bases, and are apt to polymerize and decompose. To avoid this, sodium acetate was used to adjust pH in reaction solutions. The reactions were run at weak acidic conditions (pH 4–5) at 0–5 °C, thereby preventing the polymerization of maleimides. In addition, arenediazonium tetrafluoroborates were used instead of arenediazonium chlorides in order to avoid the formation of chlorosuccinimides. Fortunately, 3-phenylsuccinimide was obtained with 78% yield (Table 1, entry 2). Under TiCl₃-free conditions, no reaction took place and only the starting material 3 was recovered (Table 1, entry 1). A survey of the literature revealed that such addition of benzenediazonium tetrafluoroborate and maleimide was, to the best of our knowledge, novel and heretofore unexplored. Several parameters were altered in an attempt to improve the yield of desired product. We found that prolonging the reaction time actually decreased yield; additionally, using other radical agents, such as SnCl₂, FeSO₄, Sm(CF₃SO₃)₂, and TiCl₄ did not allow the synthesis of 3-phenylsuccinimide (Table 1, entries 3–8). Notably, higher temperatures or a longer reaction time led to decreased yields due to polymerization and partial decomposition of maleimide. Using DMF, DMSO, THF or CH₃CN as the reaction solvent, gave unacceptably poor yields of product (Table 1, entries 14–18). The above results demonstrated that TiCl₃ is a more effective reductive arylation reagent in comparison to other metallic reagents. It should be noted that without any catalyst, the reaction did not generate the desired product at all. In addition, 3-arylmaleimide was obtained by the coupling of arenediazonium tetrafluoroborate and maleimide catalyzed by CuCl in DMF with 86% yield.

Table 1 Optimization of the reaction conditions^a

Entry	Catalyst	Solvent	Time (h)	Yield^b (4a) %	Yield^b (5a) %
a Reaction conditions: benzenediazonium tetrafluoroborate (2.0 mmol), maleimide (2.4 mmol) and catalyst (0.4 mmol) in solvent (15 mL), reaction temperature is around 0 to 25 °C.b Isolated yield.c Catalyst (4.4 mmol).
1	—	Acetone	12	0	0
2	TiCl3^c	Acetone	6	78	0
3	SnCl2^c	Acetone	6	0	0
4	FeSO4^c	Acetone	12	0	0
5	Fe2(SO4)3^c	Acetone	12	0	0
6	Sm(CF3SO3)3^c	Acetone	12	0	0
7	ZnCl2^c	Acetone	12	0	0
8	TiCl4^c	Acetone	12	0	0
9	CuCl	Acetone	6	12	54
10	CuCl	Acetone	12	15	49
11	CuCl2	Acetone	12	14	46
12	Pd(AcO)2	Acetone	12	0	33
13	PdCl2	DMSO	12	0	25
14	TiCl3^c	DMSO	12	0	0
15	TiCl3^c	H2O	6	48	0
16	TiCl3^c	THF	12	38	0
17	TiCl3^c	CH3CN	12	55	0
18	TiCl3^c	DMF	12	20	0
19	CuCl	CH3CN	6	0	0
20	CuCl	DMF	6	0	86
21	CuCl	DMSO	6	0	43

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Subsequently, the influence of the amount of TiCl₃ on the reaction was also evaluated under identical reaction conditions. Increasing the loading of TiCl₃ initially led to a sharp increase in the yield and further to a steady state. The yield approached 78% by using 200 mol% of TiCl₃ as reaction agent. This result demonstrated titanium(III) chloride reacted with benzenediazonium tetrafluoroborate and maleimide as a reaction agent, and was not serving as a catalyst.

To further illustrate the utility of this method, a series of substrates including aromatic amines and maleimides was applied to this protocol. The results are summarized in Table 2. In some cases, isolated yields were good and ranged from 60 to 83%. The aryl rings with electron-withdrawing and donating moieties gave a satisfactory yield. The former led to slightly lower yields than the latter, because of the difference of nucleophilicity. The yields of compounds 4b, 4i and 4j are lower because of the negative inductive effect of nitro and CF₃ groups (Table 2, entry 2 and 9) and the yield of compound 4f is low due to the steric hindrance of substitution in the phenyl group. The reaction provided a convenient route to prepare 3-arysuccinimide.

Table 2 TiCl₃-inducedre induced reductive ductive arylation of arenediazonium tetrafluoroborates with maleimides^a

Entry	Maleimide	ArN2BF4	Product	Time (h)	Yield^b %
a Reaction conditions: arenediazonium tetrafluoroborate (2.0 mmol), maleimide (2.4 mmol) and TiCl3 (4.4 mmol), reaction temperature 0–25 °C.b Isolated yield.
1				6	78%
2				8	67%
3				6	76%
4				6	72%
5				6	80%
6				6	60%
7				6	79%
8				6	83%
9				8	65%
10				6	62%
11				6	82%
12				6	73%

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According to our results, we believed that Ti³⁺ has played two functions in our reaction of aryldiazonium tetrafluoroborate with maleimide. A plausible mechanism is proposed for TiCl₃-induced reductive arylation in Scheme 3. First, homolytic cleavage of diazonium salts to produce aryl radicals 6 by titanium(III) salts may occur, which is also effective in reducing the α-carbonylalkyl radical adduct to maleimide for compound 7. Compound 7 was reduced by titanium(III) to generate target compound 4. So, the amount of titanium(III) chloride required for optimal reactivity is at least twice the amount of maleimides (Scheme 3).

Scheme 3 Proposed mechanism of the reaction for preparation 3-arylsuccinimides.

The 3-arylmaleimide derivatives were traditionally prepared from 3-arylsuccinimide using DDQ and MnO₂ as oxidation agents.¹¹ In 2001, a new synthesis method of α-arylmaleimide was reported by Yasuhiro through the reaction of 1,1-dis(methylthio)-2-nitroethylene with aryl cyanide followed by intramolecular interconversion, and hydrolysis, this scheme allowed α-arylmaleimides derivatives to be obtained with high yield.¹⁵ In 2008, Roshchin and Zhou reported that the Heck reaction of maleimides with aryl iodides in the presence of PdCl₂(MeCN)₂, Bu₄NCl and HCOOK afforded the corresponding 3-arylmaleimides in moderate yields.¹⁶ Classic Meerwein arylation was adopted to prepare 3-arylmaleimide using arenediazonium chloride with a low to moderate yield. Chlorosuccinimides were generated as byproducts. In 2009, Petzer provided a modified Meerwein reaction of diazonium salts and maleimide to yield chlorosuccinimides. The target N-methyl-2-phenylmaleimides were obtained following thermal dehydrohalogenation of the intermediate chlorosuccinimides in the presence of 2,6-lutidine.¹⁷ The strategy was used for the synthesis of 3-arylmaleimides.¹⁸ However, this approach is cumbersome and gave a low yields. An improved procedure was clearly necessary for their synthesis.

We investigated the Meerwein-type arylation of maleimides with arenediazonium tetrafluoroborate under neutral conditions at room temperature. After extensive experimentation and evaluation of key parameters including temperature, solvent system, concentration and reaction time, an efficient synthesis of 3-arylmaleimide was developed by the coupling of arenediazonium tetrafluoroborate and maleimide catalyzed by CuCl. Fortunately, we found this reaction worked well using DMF as the solution. The optimal reaction conditions are shown in Table 1, and the results are summarized in Table 3. In some cases, isolated yields were good and ranged from 78 to 91%. This method provided selective and tunable synthesis of 3-arylmaleimides. We can obtain the desired product (5a) in the presence of Pd(OAc)₂ and PdCl₂ at around 30% yield (Table 1, entry 12 and 13). The above results demonstrated that CuCl is a more effective catalyst in comparison to Pd(OAc)₂ and PdCl₂. DMF is a more suitable solvent for this reaction. Diarylation and Sandmeyer-type side-products were not obtained.

Table 3 CuCl-induced reaction of arenediazonium tetrafluoroborates with maleimides^a

Entry	Maleimide	ArN2BF4	Product	Time (h)	Yield^b %
a Reaction conditions: arenediazonium tetrafluoroborate (2.0 mmol), maleimide (2.4 mmol) and CuCl (0.4 mmol), reaction temperature 0–25 °C.b Isolated yield.
1				6	85%
2				6	78%
3				6	83%
4				6	84%
5				6	91%
6				6	87%
7				6	81%

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According to the reported literature,¹⁹ a possible mechanism for Meerwein arylation is proposed in Scheme 4, in which arenediazonium tetrafluoroborate was decomposed to aryl radical 6 and nitrogen by copper(I). At the same time, Cu(I) converts to Cu(II). The aryl radical coupling with maleimide generates intermediate 7. The reaction may proceed via deprotonation of 7 followed by one electron oxidation to give products 5.

Scheme 4 Proposed catalytic cycle for the reaction of arenediazonium tetrafluoroborate and maleimide catalyzed by CuCl.

In summary, we report a selective and tunable method for the arylation and reductive arylation of challenging maleimides, which are prone to undergo facile hydrolysis and polymerization. The reactions were optimized to generate the desired products in moderate to excellent yields. Apart from broad substrate scope and good functional-group compatibility, this methodology provided the selective synthesis of two classes of products by simply switching different metal reagents. This method offers one of the important motifs for the synthesis of 3-substituted succinimides and maleimides as natural products, biologically active compounds, and pharmaceutical agents. Further application of this method for the preparation of new potent bioactive molecules is ongoing in our group.

Melting points were uncorrected and were determined with RY-1 apparatus. Infrared (IR) spectra were determined as KBr pellets on a Shimadzu model 470 spectrophotometer. ¹H NMR and ¹³C NMR spectra were recorded using a Bruker AV 400 MHz spectrometer in CDCl₃ and DMSO-d₆ with tetra-methylsilane as internal standard. Chemical shifts (δ) are expressed in ppm. EI mass spectra were recorded on Shimadzu QP-2010 GC-MS system and Waters Micromass GCT system. Silica gel (100–200 microns) was used for all chromatographic separations. All materials were obtained from commercial suppliers and were used as received. The purity of substrates and the monitoring of reactions were performed by TLC on silica gel polygram SILG/UV 254 plates.

General procedure for the synthesis of aryldiazonium tetrafluoroborates

Aniline (50 mmol) was dissolved in the 40% (v/v) fluoroboric acid (200 mmol). After cooling to 0 °C, an aqueous solution of sodium nitrite (3.6 g, 51 mmol) in 15 mL H₂O was added dropwise for 20 min. The mixture was stirred for 3 h and the thick precipitate was collected and washed with diethyl ether (2 × 10 mL). The arenediazonium tetrafluoroborate was dried in vacuo (10⁻³ mbar) for 10 minutes and was then directly used without further purification.

General procedure for the synthesis of 3-arylsuccinimides 4a–4l

Sodium acetate (3 mmol) was added with stirring to a solution of 15% titanium(III) chloride (4.4 mmol) in 10 mL acetone at 10 °C. A solution of maleimide derivatives (2.4 mmol) in 5 mL acetone is added dropwise to the reaction mixture at 0 °C and then the solid arzenediazoium tetrafluoroborate (2 mmol) was added over the course of 1 hour. The nitrogen evolution stopped after 30–40 min. The cooling bath was removed. The solution was warmed to room temperature with continuous stirring and maintained for 3 hours or overnight. The solution was concentrated under vacuum to remove acetone, and extracted with ether acetate (3 × 20 mL). The combined extracts were washed with saturated sodium chloride solution, dried, evaporated to dryness, and chromatographed on silica gel (eluting with ether acetate and petroleum ether) to yield specified products 4a–4l. All of the products were known compounds, and the data of mp and ¹H NMR were in accord with those reported in the literature.

3-Phenylpyrrolidine-2,5-dione (4a)^7b

Yield: 0.27 g (78%); a white crystalline solid; mp 85–87 °C. IR (KBr): 3220, 3073, 1777, 1711, 1348, 1180, 756, 703, 641 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ: 2.82 (dd, J = 4.0, 4.0 Hz, 1H), 3.22 (dd, J = 12.0, 8.0 Hz, 1H), 4.05 (d, J = 8.0 Hz, 1H), 7.22–7.39 (m, 5H), 9.34 (s, 1H). ¹³C NMR (101 MHz, CDCl₃) δ: 38.27, 47.33, 127.44, 128.08, 129.25, 136.69, 176.66, 178.41. MS (EI): m/z 175 [M]⁺, 104, 78, 51.

3-(4-Nitrophenyl)-pyrrolidine-2,5-dione (4b)⁵

Yield: 0.29 g (67%); a yellow crystalline solid; mp 145–147 °C. IR (KBr): 3215, 1779, 1711, 1598, 1518, 1345, 1270, 1179, 855, 753 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ: 2.92 (dd, J = 4.0, 8.0 Hz, 1H), 3.33 (dd, J = 8.0, 12.0 Hz, 1H), 4.25 (d, J = 12.0 Hz, 1H), 7.48 (d, J = 8.0 Hz, 2H), 8.26 (d, J = 8.0 Hz, 2H), 8.40 (s, 1H). ¹³C NMR (101 MHz, CDCl₃) δ: 37.59, 46.86, 124.43, 128.57, 143.31, 147.72, 174.70, 176.06. MS (EI): m/z 220 [M]⁺, 177, 149, 119, 103, 91, 77.

3-(4-Chlorophenyl)-pyrrolidine-2,5-dione (4c)²⁰

Yield: 0.32 g (76%); a yellow crystalline solid; mp 128–130 °C. IR (KBr): 3204, 1780, 1711, 1491, 1384, 1180, 1092, 825, 741, 671 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ: 2.86 (dd, J = 4.0, 8.0 Hz, 1H), 3.27 (dd, J = 8.0, 12.0 Hz, 1H), 4.09 (d, J = 12.0 Hz, 1H), 7.22 (d, J = 8.0 Hz, 2H), 7.38 (d, J = 8.0 Hz, 2H), 8.74 (s, 1H). ¹³C NMR (101 MHz, CDCl₃) δ: 38.00, 46.64, 128.81, 129.43, 134.15, 134.90, 175.90, 177.60. MS (EI): m/z 209 [M]⁺, 138, 103, 77, 51.

3-(4-Bromophenyl)-pyrrolidine-2,5-dione (4d)²¹

Yield: 0.36 g (72%); a yellow crystalline solid; mp 130–132 °C. IR (KBr): 3198, 1701, 1482, 1346, 1181, 820, 730, 629 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ: 2.87 (dd, J = 4.0, 8.0 Hz, 1H), 3.28 (dd, J = 8.0, 12.0 Hz, 1H), 4.09 (d, J = 12.0 Hz, 1H), 7.17 (d, J = 8.0 Hz, 2H), 7.52 (d, J = 8.0 Hz, 2H), 8.52 (s, 1H). ¹³C NMR (101 MHz, CDCl₃) δ: 37.93, 46.71, 122.23, 129.13, 132.40, 135.41, 175.65, 177.29. MS (EI): m/z 255 [M]⁺, 182, 103, 77, 51.

3-(4-Methoxyphenyl)-pyrrolidine-2,5-dione (4e)^7b

Yield: 0.33 g (80%); a yellow crystalline solid; mp 135–137 °C. IR (KBr): 3220, 1778, 1708, 1513, 1347, 1249, 1177, 1029, 828, 698 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ: 2.83 (dd, J = 4.0, 8.0 Hz, 1H), 3.21 (dd, J = 8.0, 12.0 Hz, 1H), 3.80 (s, 3H), 4.02 (d, J = 12.0 Hz, 1H), 6.90 (d, J = 8.0 Hz, 2H), 7.16 (d, J = 8.0 Hz, 2H), 8.79 (s, 1H). ¹³C NMR (101 MHz, CDCl₃) δ: 38.32, 46.59, 55.36, 114.66, 128.52, 128.62, 159.34, 176.51, 178.54. MS (EI): m/z 205 [M]⁺, 134, 119, 91, 65.

3-(2-Chloro-6-methylphenyl)-pyrrolidine-2,-5-dione (4f)

Yield: 0.26 g (60%); a yellow crystalline solid; mp 152–155 °C. IR (KBr): 3214, 3076, 1779, 1711, 1459, 1348, 1273, 1178, 859, 778, 731 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ: 2.25, 2.43 (s, 3H), 2.74, 3.02 (dd, J = 4.0, 8.0 Hz, 1H), 3.14, 3.25 (dd, J = 8.0, 12.0 Hz, 1H), 4.42, 5.01 (d, J = 8.0 Hz, 1H), 7.16–7.28 (m, 3H), 8.60 (s, 1H). ¹³C NMR (101 MHz, CDCl₃) δ: 21.09, 36.09, 43.16, 128.67, 129.14, 129.37, 132.48, 133.82, 139.62, 175.93, 177.67. HRMS (EI): m/z [M]⁺ calcd for C₁₁H₁₀NO₂Cl, 223.0400; found, 223.0402.

3-(Naphthalen-1-yl)-pyrrolidine-2,5-dione (4g)^7b

Yield: 0.35 g (79%); a yellow crystalline solid; mp 150–152 °C. IR (KBr): 3222, 3066, 1775, 1709, 1349, 1268, 1183, 781, 734, 694, 630 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ: 2.72 (dd, J = 4.0, 8.0 Hz, 1H), 3.23 (dd, J = 8.0, 12.0 Hz, 1H), 4.97 (d, J = 12.0 Hz, 1H), 7.42 (d, J = 8.0 Hz, 1H), 7.51 (t, J = 8.0 Hz, 1H), 7.55–7.63 (m, 2H), 7.90 (d, J = 8.0 Hz, 1H), 7.99 (d, J = 8.0 Hz, 2H), 11.54 (s, 1H). ¹³C NMR (101 MHz, DMSO-d₆) δ: 38.92, 44.22, 123.89, 125.65, 126.09, 126.42, 127.02, 128.30, 129.28, 131.73, 134.06, 135.10, 178.11, 180.23. MS (EI): m/z 225 [M]⁺, 154, 126, 102, 76, 51.

1-Methyl-3-phenylpyrrolidine-2,5-dione (4h)²²

Yield: 0.31 g (83%); a white crystalline solid; mp 70–72 °C. IR (KBr): 2944, 1773, 1702, 1437, 1381, 1282, 1119, 952, 806, 474 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ: 2.86 (dd, J = 4.0, 8.0 Hz, 1H), 3.10 (s, 3H), 3.24 (dd, J = 8.0, 12.0 Hz), 4.05 (d, J = 8.0 Hz), 7.24–7.26 (m, 2H), 7.31–7.37 (m, 3H). ¹³C NMR (101 MHz, CDCl₃) δ: 25.22, 37.13, 45.97, 127.38, 127.97, 129.20, 137.08, 176.22, 177.79. MS (EI): m/z 189 [M]⁺, 104, 78.

3-(4-Nitrophenyl)-1-phenylpyrrolidine-2,5-dione (4i)²³

Yield: 0.38 g (65%); a white crystalline solid; mp 118–120 °C. IR (KBr): 3070, 1779, 1712, 1599, 1511, 1385, 1347, 1183, 857, 750, cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ: 3.04 (dd, J = 4.0, 8.0 Hz, 1H), 3.46 (dd, J = 9.8, 18.5 Hz, 1H), 4.35 (d, J = 8.0 Hz, 1H), 7.33 (d, J = 8.0 Hz, 2H), 7.45 (d, J = 8.0 Hz, 1H), 7.51–7.55 (m, 4H), 8.29 (d, J = 8.0 Hz, 2H). ¹³C NMR (101 MHz, CDCl₃) δ: 36.60, 45.62, 124.48, 126.34, 128.63, 129.04, 129.36, 131.52, 143.83, 147.70, 174.06, 175.28. MS (EI): m/z 296 [M]⁺, 175, 149, 119, 103, 91, 77.

3-(3-Chloro-4-trifluoromethylphenyl)-1-phenylpyrrolidine-2,5-dione (4j)

Yield: 0.43 g (62%); a white crystalline solid; mp 155–157 °C. IR (KBr): 1711, 1488, 1395, 1321, 1269, 1193, 1140, 1033, 749 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ: 3.01 (dd, J = 4.0, 8.0 Hz, 1H), 3.45 (dd, J = 8.0, 12.0 Hz, 1H), 4.28 (d, J = 8.0 Hz, 1H), 7.34–7.47 (m, 2H), 7.44 -7.60 (m, 5H), 7.69 (s, 1H). ¹³C NMR (101 MHz, CDCl₃) δ: 36.59, 45.09, 121.13, 123.85, 126.35, 126.90, 129.00, 129.34, 131.54, 131.81, 132.33, 132.39, 135.77, 174.07, 175.49. HRMS (EI): m/z [M]⁺ calcd for C₁₇H₁₁NO₂F₃Cl, 353.0430; found, 253.0426.

3-(4-Methoxyphenyl)-1-phenylpyrrolidine-2,5-dione (4k)²⁴

Yield: 0.46 g (82%); a white crystalline solid; mp 170–172 °C. IR (KBr): 1709, 1606, 1504, 1456, 1241, 1194, 1030, 737, 694 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ: 2.89 (dd, J = 4.0, 8.0 Hz, 1H), 3.25 (dd, J = 8.0, 12.0 Hz, 1H), 3.73 (s, 3H), 4.26 (d, J = 8.0 Hz, 1H), 6.92 (d, J = 8.0 Hz, 2H), 7.31–7.33 (m, 4H), 7.39–7.41 (m, 1H), 7.47–7.51 (m, 2H). ¹³C NMR (101 MHz, DMSO-d₆) δ: 37.67, 45.51, 55.60, 114.61, 127.69, 128.78, 129.33, 129.73, 130.31, 133.14, 159.03, 175.93, 177.96. MS (EI): m/z 281 [M]⁺, 134, 119, 91, 65.

3-(4-Methoxyphenyl)-1-benzylpyrrolidine-2,5-dione (4l)²²

Yield: 0.43 g (73%); a white crystalline solid; mp 108–110 °C. IR (KBr): 1702, 1511, 1394, 1344, 1250, 1165, 1032, 833, 702 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ: 2.81 (dd, J = 4.0, 8.0 Hz, 1H), 3.23 (dd, J = 8.0, 12.0 Hz, 1H), 3.73 (s, 3H), 4.19 (d, 8.0 Hz, 1H), 4.61 (s, 2H), 6.90 (d, J = 8.0 Hz, 2H), 7.18–7.20 (d, J = 8.0 Hz, 2H), 7.26–7.32 (m, 3H), 7.33 (t, J = 8.0 Hz, 2H). ¹³C NMR (101 MHz, DMSO-d₆) δ: 37.22, 42.11, 45.16, 55.59, 114.59, 127.88, 128.97, 129.48, 130.18, 136.71, 158.98, 176.66, 178.56. MS (EI): m/z 295 [M]⁺, 187, 162, 134, 119, 91, 65.

General procedure for the synthesis of 3-arylmaleimide 5a–5g

Arzenediazoium tetrafluoroborate is (2 mmol) was added to an ice-cold suspension of maleimide derivative (2.4 mmol) and cuprous chloride (0.4 mmol) in 5 mL DMF. Evolution of nitrogen began almost immediately in most cases. After 0.5 hour at 0–5 °C, the mixture was warmed to room temperature with continuous stirring and there maintained for 6 hours or overnight. The mixture was added to 10 mL H₂O and extracted with ether acetate (3 × 20 mL). The combined extracts were washed with saturated sodium chloride solution, dried, evaporated to dryness, and chromatographed on silica gel (eluting with ether acetate and petroleum ether) to yield specified products 5a–5g. All of the products were known compounds, and the data of mp and ¹H NMR were in accord with those reported in the literature.

3-Phenyl-1H-pyrrole-2,5-dione (5a)^15b

Yield: 0.29 g (85%); a yellow crystalline solid (85% yield); mp 167–168 °C. IR (KBr): 3351, 3199, 1727, 1339, 1186, 1125, 1012, 819, 736 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ: 7.18 (s, 1H), 7.50 (d, J = 8.0 Hz, 2H), 7.98 (d, J = 8.0 Hz, 2H), 11.03 (s, 1H). ¹³C NMR (101 MHz, DMSO-d₆) δ: 126.33, 129.06, 129.23, 129.44, 131.16, 143.53, 172.15, 172.63. MS (EI): m/z 173 [M]⁺, 102, 76, 51.

3-(4-Chloro-3-trifluoromethylphenyl)-1H-pyrrole-2,5-dione (5b)

Yield: 0.42 g (78%); a yellow crystalline solid; mp 218–220 °C. IR (KBr): 3351, 3183, 1721, 1602, 1395, 1333, 1253, 1128, 1020, 937, 880, 829, 704 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ: 7.42 (s, 1H), 7.88 (d, J = 8.0 Hz, 1H), 8.26 (d, J = 8.0 Hz, 1H), 8.45 (s, 1H), 11.18 (s, 1H). ¹³C NMR (101 MHz, DMSO-d₆) δ: 121.70, 124.41, 128.08, 128.53, 129.08, 132.67, 133.20, 134.39, 140.92, 171.71, 172.24. HRMS (EI): m/z [M]⁺ calcd for C₁₁H₅NO₂F₃Cl, 274.9960; found, 274.9961.

3-(4-Bromophenyl)-1H-pyrrole-2,5-dione (5c)^10b

Yield: 0.41 g (83%); a yellow crystalline solid; mp 206–209 °C. IR (KBr): 3350, 3196, 1726, 1484, 1392, 1341, 1185, 1123, 1009, 821, 743 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ: 7.24 (s, 1H), 7.72 (d, J = 8.0 Hz, 2H), 7.95 (d, J = 8.0 Hz, 2H), 11.07 (s, 1H). ¹³C NMR (101 MHz, DMSO-d₆) δ: 124.95, 126.92, 128.66, 130.98, 132.31, 142.37, 171.98, 172.43. MS (EI): m/z 251 [M]⁺, 180, 101, 75, 50.

3-(4-Chlorophenyl)-1H-pyrrole-2,5-dione (5d)^15b

Yield: 0.34 g (84%); a yellow crystalline solid; mp 178–180 °C. IR (KBr): 3204, 1723, 1644, 1345, 1188, 1015, 875, 822, 749 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ: 7.23 (s, 1H), 7.58 (d, J = 8.0 Hz, 2H), 8.02 (d, J = 8.0 Hz, 2H), 11.06 (s, 1H). ¹³C NMR (101 MHz, DMSO-d₆) δ: 126.88, 128.33, 129.38, 130.81, 136.00, 142.26, 171.98, 172.48. MS (EI): m/z 207 [M]⁺, 136, 101, 75, 50.

3-(4-Methoxyphenyl)-1H-pyrrole-2,5-dione (5e)^15b

Yield: 0.37 g (91%); a yellow crystalline solid; mp 176–178 °C. IR (KBr): 3351, 3193, 1725, 1595, 1501, 1335, 1253, 1179, 1126, 1016, 828, 734 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ: 3.90 (s, 3H), 6.62 (s, 1H, CH), 7.00 (d, J = 8.0 Hz, 2H), 7.41 (s, 1H), 7.96 (d, J = 8.0 Hz, 2H). ¹³C NMR (101 MHz, CDCl₃) δ: 55.46, 114.54, 121.17, 121.72, 130.54, 135.13, 144.22, 162.19, 170.10, 170.82. MS (EI): m/z 203 [M]⁺, 132, 117, 89, 63, 51.

3-(4-Bromophenyl)-1-phenyl-1H-pyrrole-2,5-dione (5f)

Yield: 0.56 g (87%); a yellow crystalline solid; mp 150–152 °C. IR (KBr): 3029, 1704, 1597, 1493, 1395, 1208, 1132, 1073, 1008, 824 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ: 7.39–7.44 (m, 3H), 7.50–7.54 (m, 3H), 7.77 (d, J = 8.0 Hz, 2H), 8.03 (d, J = 8.0 Hz, 2H). ¹³C NMR (101 MHz, DMSO-d₆) δ: 125.30, 126.26, 127.50, 128.30, 128.54, 129.33, 131.06, 132.15, 132.45, 142.02, 169.55, 169.74. MS (EI): m/z 327 [M]⁺, 248, 182, 101, 75, 63, 51. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₆H₁₁NO₂Br, 327.9968; found, 327.9964.

3-(4-Nitrophenyl)-1H-pyrrole-2,5-dione (5g)²⁵

Yield: 0.35 g (81%); a yellow crystalline solid; mp 195–197 °C. IR (KBr): 3233, 3087, 1697, 1591, 1508, 1345, 1127, 917, 863, 747, 675 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ: 7.44 (s, 1H), 8.23 (d, J = 8.7 Hz, 2H), 8.34 (d, J = 8.7 Hz, 2H), 11.22 (s, 1H). ¹³C NMR (101 MHz, DMSO-d₆) δ: 124.23, 129.89, 130.31, 135.60, 141.39, 148.63, 171.63, 172.10. MS (EI): m/z 218 [M]⁺, 175, 147, 117, 89, 51.

Acknowledgements

The authors acknowledge financial support from Shanghai Manucipical Natural Science Foundation (No. 15ZR1401400) and the Open Funds from the State Key Laboratory of Bioorganic & Natural products Chemistry in Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences (2013) and the Fundamental Research Funds for the Central Universities from the Ministry of Education of China (CUSF-DH-D-2015048 and CUSF-DH-D-2016028) for financial support. We are grateful to Mr William Alborn for reviewing and editing this article.

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Footnotes

† Electronic supplementary information (ESI) available: NMR spectra of all the final compounds. See DOI: 10.1039/c6ra00136j

‡ These authors contributed equally to this work.

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