Tin(IV) chloride mediated (3 + 2) annulation of trans-2-aroyl-3-styrylcyclopropane-1,1-dicarboxylates with nitriles: diastereoselective access to 5-vinyl-1-pyrroline derivatives

Abstract

A tin(IV) chloride promoted (3 + 2) annulation of trans-2-aroyl-3-styrylcyclopropane-1,1-dicarboxylates with nitriles is reported. The transformation involves the Lewis acid assisted formation of 1,5-dipolar intermediates from the cyclopropane dicarboxylates and nitriles followed by cyclization. The reactions proceed in a highly diastereoselective manner and afford 5-vinyl-1-pyrroline derivatives in 60–88% yields.

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Introduction

The annulation (formal cycloaddition) reactions of donor–acceptor (D–A) cyclopropanes are one of the efficient tools for the construction of various carbocyclic and heterocyclic compounds.¹ The merits of the methodology include excellent stereoselectivity, atom economy and formation of products in good yields with diverse functionality. Due to their merits, few of the methods have been employed as key steps in the total synthesis of various biologically important natural products.²

1-Pyrrolines are an important class of heterocyclic compounds as the core is present in a notable number of natural products and biologically relevant compounds.³ They also serve as versatile synthetic intermediates for the access of pharmaceutically important compounds.⁴ So numerous approaches have been developed for the synthesis of 1-pyrrolines.⁵ The (3 + 2) annulation of D–A cyclopropanes with nitriles is a versatile strategy for the stereoselective synthesis of 1-pyrrolines.⁶

Few years back, we reported that aroyl substituted D–A cyclopropanes 1 undergo SnCl₄-promoted (3 + 2) annulation with nitriles 2 to give 1-pyrrolines 3 diastereoselectively (Scheme 1, eqn (1)).⁷ Recently, we reported a similar approach for the access of γ-butyrolactone-fused 1-pyrrolines 5 from γ-butyrolactone-fused D–A cyclopropanes 4 (Scheme 1, eqn (2)).⁸ Meanwhile, we have also synthesized and explored the synthetic potential of a similar class of aroyl substituted D–A cyclopropanes having aryl vinyl donor group, namely, trans-2-aroyl-3-styrylcyclopropane-1,1-dicarboxylates 6.⁹ Naturally, we became interested in exploring the (3 + 2) annulation of 6 with various nitriles with a view to obtain vinyl-substituted 1-pyrroline derivatives 7 (Scheme 1, eqn (3)). It is interesting to note that the vinyl pyrroline core is present in alkaloids isolated from the venom of the myrmicine ant Megalomyrmex foreli of Costa Rica.¹⁰

Scheme 1 Comparison of the present work with our previous works.

Results and discussion

To identify optimal reaction conditions for the (3 + 2) annulation of trans-2-aroyl-3-styrylcycyopropane-1,1-dicarboxylates with nitriles, we selected cyclopropane 6a and benzonitrile (2a) as model substrates and reacted under the optimized conditions previously reported for similar D–A cyclopropanes 1 (Table 1, entry 1).⁷ Accordingly, when 1 equiv. of 6a was treated with 5 equiv. of 2a in the presence of 1 equiv. of SnCl₄ in 1,2-dichloroethane (1,2-DCE) at room temperature for 12 h, the expected vinyl 1-pyrroline product was produced in 86% yield (entry 1). Normally, an excess amount of nitrile (2.5 to 5 equiv.) was used in cyclopropane-nitrile annulations for achieving better yields.⁶ In the present case, we observed that the use of 2.5 equiv. of 2a was enough to obtain the same yield (entry 2). So, in the subsequent experiments, we used only 2.5 equiv. of 2a. Next, we reduced the amount of SnCl₄ to 0.2 or 0.5 equiv., but the yield of 7a was also decreased to 10 and 58%, respectively (entries 3 and 4). When the amount of SnCl₄ was increased to 1.5 or 2 equiv., again the yield of 6a was decreased owing to the formation of more impurities (entries 5 and 6). The yield of 7a also decreased when the reaction was carried out at 0 °C or 60 °C (entries 7 and 8). Switching the solvent to dichloromethane, nitromethane or toluene also gave only a lower yield of 7a while the reaction did not take place in THF (entries 9–12). We also investigated the suitability of other tin sources for the transformation. When SnCl₄·5H₂O was used, the reaction gave a complicated mixture of products (entry 13) while the reaction did not take place with SnCl₂ (entry 14). We also tested other Lewis acids for the transformation. The use of AlCl₃ reduced the yield of 7a to 70% while TiCl₄ gave only trace amount of 7a (entries 15 and 16). Upon using BF₃·OEt₂, the cyclopropane 6a did not react with 2a; instead, it underwent fragmentation to give cinnamaldehyde and phenacyl malonate (entry 17).^9a When other Lewis acids such as InCl₃, In(OTf)₃, Cu(OTf)₂, Sc(OTf)₃ and Yb(OTf)₃ were used, the transformation did not take place (entries 18–22). Also, the reaction did not work when a Bronsted acid, viz., p-TSOH was used (entry 23). So we chose treating 1 equiv. of 6a with 2.5 equiv. of 2a in the presence of 1 equiv. of SnCl₄ in 1,2-DCE at room temperature as optimal condition for the formation of 7a in a better yield.

Table 1 Optimization of the reaction conditions for the [3 + 2] annulation^a

Entry	Reagents (equiv.) and conditions^a	Yield of 7a^b (%)
a The reaction was conducted with 1a (1 equiv.), 2a (2.5 equiv.), Lewis acid (n equiv.) and solvent (3 mL).b Isolated yield.c No reaction.d Complicated mixture of products.e 6a underwent fragmentation to give cinnamaldehyde and phenacyl malonate.^9a
1	SnCl4 (1.0), 1,2-DCE, rt, 12 h [using 2a (5 equiv.)]	86
2	SnCl4 (1.0), 1,2-DCE, rt, 12 h	86
3	SnCl4 (0.2), 1,2-DCE, rt, 12 h	10
4	SnCl4 (0.5), 1,2-DCE, rt, 12 h	58
5	SnCl4 (1.5), 1,2-DCE, rt, 12 h	65
6	SnCl4 (2.0), 1,2-DCE, rt, 12 h	62
7	SnCl4 (1.0), 1,2-DCE, 0 °C, 12 h	55
8	SnCl4 (1.0), 1,2-DCE, 60 °C, 12 h	46
9	SnCl4 (1.0), CH2Cl2, rt, 12 h	30
10	SnCl4 (1.0), MeNO2, rt, 12 h	10
11	SnCl4 (1.0), PhMe, rt, 12 h	30
12	SnCl4 (1.0), THF, rt, 24 h	NR^c
13	SnCl4·5H2O (1.0), 1,2-DCE, rt, 12 h	c.m.^d
14	SnCl2 (1.0), 1,2-DCE, rt, 24 h	NR^c
15	AlCl3 (1.0), 1,2-DCE, rt, 12 h	70
16	TiCl4 (1.0), 1,2-DCE, rt, 12 h	Trace
17	BF3·Et2O (1.0), 1,2-DCE, rt, 12 h	—^e
18	InCl3 (1.0), 1,2-DCE, rt, 24 h	NR^c
19	In(OTf)3 (1.0), 1,2-DCE, rt, 24 h	NR^c
20	Cu(OTf)2 (1.0), 1,2-DCE, rt, 24 h	NR^c
21	Sc(OTf)3 (1.0), 1,2-DCE, rt, 24 h	NR^c
22	Yb(OTf)3 (1.0), 1,2-DCE, rt, 24 h	NR^c
23	p-TsOH (1.0), 1,2-DCE, rt, 24 h	NR^c

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Next, we examined the scope of the transformation for various vinyl D–A cyclopropanes and ntriles and the results are summarized in Table 2. Initially, we tested the reactions of cyclopropane 6a with aromatic nitriles 2a–d having electron donating and electron withdrawing substituents on the aryl ring (entries 1–4). Except for the reaction in entry 4, in which the expected product was not detected, all other reactions afforded the corresponding 5-vinyl-1-pyrroline derivatives 7a–c in 66–75% yields. When 6a was reacted with nitriles 2e and 2f having bulky 1-naphthyl and heteroaromatic 2-thienyl rings, vinyl 1-pyrrolines 7d and 7e were formed in 76 and 80% yields, respectively (entries 5 and 6). We also reacted cyclopropane 6a with an aliphatic nitrile, viz., acetonitrile (2g) and obtained the corresponding 1-pyrroline derivative 7f in 88% yield (entry 7). Next, we reacted cyclopropanes 6b–g having different aromatic rings as Ar¹ or Ar² with benzonitrile (2a) and obtained the respective 1-pyrrolines 7g–l in 63–78% yields (entries 8–13). Finally, we reacted various substrates having different Ar¹, Ar² or R groups and obtained the corresponding 1-pyrrolines 7m–q in 60–86% yields (entries 14–18).

Table 2 Scope of the reaction

Entry	Ar^1, Ar^2	R	Yield of 7^a (%)
a Isolated yield.b Not detected.
1	Ph, Ph (6a)	Ph (2a)	86 (7a)
2	Ph, Ph (6a)	4-MeC6H4 (2b)	75 (7b)
3	Ph, Ph (6a)	4-MeOC6H4 (2c)	66 (7c)
4	Ph, Ph (6a)	4-O2NC6H4 (2d)	n.d.^b
5	Ph, Ph (6a)	1-Naphthyl (2e)	76 (7d)
6	Ph, Ph (6a)	2-Thienyl (2f)	80 (7e)
7	Ph, Ph (6a)	Me (2g)	88 (7f)
8	4-MeOC6H4, Ph (6b)	Ph (2a)	78 (7g)
9	2-Naphthyl, Ph (6c)	Ph (2a)	76 (7h)
10	2-Thienyl, Ph (6d)	Ph (2a)	72 (7i)
11	Ph, 4-MeC6H4 (6e)	Ph (2a)	69 (7j)
12	Ph, 4-MeOC6H4 (6f)	Ph (2a)	63 (7k)
13	Ph, 4-O2NC6H4 (6g)	Ph (2a)	68 (7l)
14	4-MeC6H4, Ph (6h)	4-MeC6H4 (2b)	78 (7m)
15	4-MeC6H4, Ph (6h)	4-BrC6H4 (2h)	60 (7n)
16	4-MeC6H4, Ph (6h)	Me (2g)	80 (7o)
17	4-O2NC6H4, Ph (6i)	2-Thienyl (2f)	65 (7p)
18	4-MeC6H4, 4-MeC6H4 (6j)	Me (2g)	86 (7q)

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We propose a mechanism depicted in Scheme 2 for the formation of vinyl 1-pyrrolines 7 from D–A cyclopropanes 6 and nitriles 2 based on earlier reports.^7,8,11 Accordingly, the Lewis acid (SnCl₄) complexes with malonate unit of 6, which facilitates the nucleophilic attack of 2 on 6 at the carbon (C-3) attached to vinyl unit. In the resulting 1,5-dipolar intermediate, the groups attached to C-3 undergo 120° rotation which brings the nitrile carbon and the malonate carbanion in close proximity for cyclization. It may be noted that the rotation also brings Ar¹ and Ar² groups to a cis-position. So the product 1-pyrroline 7 is formed in a diastereoselective manner.

Scheme 2 Mechanism for the formation of vinyl 1-pyrrolines 7.

The vinyl 1-pyrroline products synthesized in the present study could serve as potential synthetic precursors for other compounds. To prove the point, we treated vinyl 1-pyrroline 7b with water in the presence of 1 equiv. of SnCl₄ in 1,2-DCE for 8 h. It underwent nucleophilic addition of water followed by ring-opening to furnish the multifunctional malonate 8 in 76% yield (Scheme 3; the structure of 8 was confirmed by X-ray analysis¹²).

Scheme 3 Synthetic application of a vinyl 1-pyrroline.

Conclusions

In summary, we have developed a convenient method for the generation of vinyl 1-pyrroline derivatives from trans-2-aroyl-3-styrylcyclopropane-1,1-dicarboxylates and nitriles. The method involves a [3 + 2] annulation between the reactants and affords the products in good yields with excellent diastereoselectivity. The products could serve as potential precursors for other compounds as exemplified by the formation of a multifunctional malonate from one of the products.

Experimental section

General procedure for the synthesis of vinyl 1-pyrrolines 7

To a solution of 2-aroyl-3-styrylcyclopropane-1,1-dicarboxylate 6 (1.0 mmol) and nitrile 2 (2.5 mmol) in 1,2-dichloroethane (3 mL) was added SnCl₄ (1.0 mmol, 0.261 g) and the reaction mixture was stirred at room temperature. After completion of the reaction (12 h), the reaction mixture was quenched with water and extracted with dichloromethane. The organic layer was washed with brine (2 × 10 mL), dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. The crude product was purified by column chromatography using EtOAc/hexane (1 : 9) to afford vinyl 1-pyrroline 7.

Diethyl 4-benzoyl-2-phenyl-5-styryl-4,5-dihydropyrrole-3,3-dicarboxylate (7a)

Yellow oily liquid. Yield: 427 mg (86%). ¹H NMR (400 MHz, CDCl₃): δ 7.91 (d, J = 8.0 Hz, 4H), 7.62–7.38 (m, 10H), 7.14–7.02 (m, 3H), 6.37 (q, J = 16.0 Hz, 1H), 5.50 (t, J = 6.6 Hz, 1H), 5.01, (d, J = 6.0 Hz, 1H), 4.31–4.24 (m, 2H), 4.00–3.94 (m, 2H), 1.21 (t, J = 7.2 Hz, 3H), 1.01 (t, J = 7.2 Hz, 3H) ppm. ¹³C NMR (400 MHz, CDCl₃): δ 196.5, 167.8, 166.0, 161.0, 147.8, 137.5, 136.8, 133.8, 133.7, 132.7, 132.5, 130.9, 130.0, 129.0, 128.8, 128.6, 128.3, 127.8, 127.7, 127.4, 124.5, 75.0, 74.7, 63.3, 62.4, 59.7, 13.8, 13.5 ppm. HRMS (ESI-TOF) m/z: [M + MeOH + H]⁺ calcd for C₃₂H₃₄NO₆, 528.2375; found: 528.2380.

Diethyl 4-benzoyl-5-styryl-2-p-tolyl-4,5-dihydropyrrole-3,3-dicarboxylate (7b)

Light yellow liquid. Yield: 382 mg (75%). ¹H NMR (400 MHz,CDCl₃): δ 7.84–7.80 (m, 4H), 7.30–7.11 (m, 11H), 6.49 (d, J = 16.0 Hz, 1H), 6.15–6.09 (m, 1H), 5.48–5.44 (m, 1H), 5.25 (d, J = 8.8 Hz, 1H), 4.36–4.20 (m, 4H), 2.43 (s, 3H), 1.22 (t, J = 7.2 Hz, 3H), 1.17 (t, J = 7.2 Hz, 3H) ppm. ¹³C NMR (400 MHz, CDCl₃): δ 195.5, 168.3, 168.2, 167.7, 144.2, 140.7, 136.8, 135.0, 132.1, 131.1, 129.9, 129.0, 128.53, 128.49, 128.3, 127.5, 126.6, 126.6, 75.0, 73.3, 62.6, 62.1, 59.1, 21.7, 13.8, 13.7 ppm. MS (ESI-TOF): m/z 544.19 [M + Cl]⁻. Anal. calcd for C₃₂H₃₁NO₅: C 75.42, H 6.13, N 2.75; found: C 75.78, H 6.25, N 2.68.

Diethyl 4-benzoyl-2-(4-methoxyphenyl)-5-styryl-4,5-dihydro-pyrrole-3,3-dicarboxylate (7c)

Pale yellow liquid. Yield: 347 mg (66%). ¹H NMR (400 MHz, CDCl₃): δ 7.91 (d, J = 7.2 Hz, 2H), 7.73 (d, J = 8.8 Hz, 2H), 7.50–7.13 (m, 8H), 6.80 (d, J = 9.2 Hz, 2H), 6.61 (d, J 15.6 Hz, 1H), 6.27 (q, J = 16.0 Hz, 1H), 5.38 (t, J = 7.0 Hz, 1H), 4.81 (d, J = 7.6 Hz, 1H), 4.11–3.91 (m, 4H), 3.75 (s, 3H), 1.03 (t, J = 7.2 Hz, 3H), 0.95 (t, J = 7.2 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 191.3, 168.9, 167.4, 159.4, 142.3, 142.1, 136.4, 133.4, 130.6, 129.6, 128.6, 126.2, 113.7, 76.7, 71.5, 64.4, 62.1, 60.5, 55.3, 13.74, 13.70 ppm. MS (ESI-TOF): m/z 524.21 [M − H]⁻. Anal. calcd for C₃₂H₃₁NO₆: C 73.13, H 5.94, N 2.66; found: C 73.35, H 5.85, N 2.72.

Diethyl 4-benzoyl-2-naphthalen-1-yl-5-styryl-4,5-dihydro-pyrrole-3,3-dicarboxylate (7d)

Yellow oily liquid. Yield: 414 mg (76%). ¹H NMR (400 MHz, CDCl₃): δ 8.09 (d, J = 8.4 Hz, 1H), 7.90–7.76 (m, 4H), 7.49–7.36 (m, 3H), 7.17–7.00 (m, 5H), 6.51 (d, J = 15.6 Hz, 1H), 5.85 (s, 1H), 5.00 (d, J = 8.4 Hz, 1H), 4.82 (t, J = 7.6 Hz, 1H), 3.97–3.25 (m, 4H), 1.19 (t, J = 7.2 Hz, 3H), 0.80 (t, J = 7.2 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 192.7, 172.14, 172.09, 167.5, 144.3, 143.7, 138.5, 136.5, 133.4, 129.7, 128.58, 128.57, 128.43, 128.40, 128.1, 127.7, 114.8, 114.3, 81.9, 72.6, 72.58, 63.0, 61.4, 60.0, 13.8, 13.4, ppm. MS (ESI-TOF): m/z 566.18 [M + Na–2H]⁻. Anal. calcd for C₃₅H₃₁NO₅: C 77.04, H 5.73, N 2.57; found: C 77.28, H 5.67, N 2.69.

Diethyl 4-benzoyl-5-styryl-2-thiophen-2-yl-4,5-dihydro-pyrrole-3,3-dicarboxylate (7e)

Brown oily liquid. Yield: 401 mg (80%). ¹H NMR (400 MHz, CDCl₃): δ 8.01 (d, J = 7.2 Hz, 2H), 7.92–7.36 (m, 11H), 7.14–7.02 (m, 1H), 6.40–6.34 (m, 1H), 5.50 (t, J = 6.8 Hz, 1H), 5.01 (d, J = 6.0 Hz, 1H), 4.31–4.24 (m, 2H), 3.97 (q, J = 7.2 Hz, 2H), 1.21 (t, J = 7.2 Hz, 3H), 1.01 (t, J = 7.2 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 198.0, 168.3, 167.8, 150.2, 142.0, 141.1, 135.6, 134.0, 129.6, 128.5, 128.3, 126.7, 126.5, 125.9, 124.89, 124.86, 124.0, 82.7, 81.5, 69.7, 62.5, 62.0, 57.9, 13.8, 13.5 ppm. MS (ESI-TOF): m/z 502.18 [M + H]⁺. Anal. calcd for C₂₉H₂₇NO₅S: C 69.44, H 5.43, N 2.79; found: C 69.76, H 5.55, N 2.88.

Diethyl 4-benzoyl-2-methyl-5-styryl-4,5-dihydropyrrole-3,3-dicarboxylate (7f)

Yellow oily liquid. Yield: 381 mg (88%). ¹H NMR (400 MHz, CDCl₃): δ 7.78 (d, J = 7.6 Hz, 2H), 7.45–7.06 (m, 8H), 6.93–6.91 (m, 2H), 6.42 (d, J = 16.0 Hz, 1H), 5.79 (q, J = 15.6 Hz, 1H), 5.19 (t, J = 9.2 Hz, 1H), 5.08 (d, J = 7.2 Hz, 1H), 4.25–4.04 (m, 4H), 2.43 (s, 3H), 1.24 (t, J = 7.2 Hz, 3H), 1.01 (t, J = 7.2 Hz, 3H) ppm. ¹³C NMR (400 MHz, CDCl₃): δ 197.8, 166.9, 166.7, 137.6, 136.6, 133.3, 133.2, 128.8, 128.7, 128.6, 128.5, 128.2, 127.5, 126.5, 126.5, 75.1, 74.1, 62.9, 61.8, 56.9, 18.9, 14.0, 13.7 ppm. MS (ESI-TOF): m/z 512.27 [M + DMSO + H]⁺. Anal. calcd for C₂₆H₂₇NO₅: C 72.04, H 6.28, N 3.23; found: C 72.33, H 6.40, N 3.36.

Diethyl 4-benzoyl-5-[2-(4-methoxyphenyl)-vinyl]-2-phenyl-4,5-dihydropyrrole-3,3-dicarboxylate (7g)

Yellow oily liquid. Yield: 410 mg (78%). ¹H NMR (400 MHz, CDCl₃): δ 7.99 (d, J = 7.2 Hz, 2H), 7.60–7.26 (m, 11H), 6.95 (d, J = 8.8 Hz, 1H), 6.62 (d, J = 15.2 Hz, 1H), 6.27 (q, J = 16.0 Hz, 1H), 5.19 (t, J = 7.6 Hz, 1H), 4.75 (q, J = 8.8 Hz, 1H), 4.30–4.16 (m, 4H), 3.86 (s, 3H), 1.27 (t, J = 7.2 Hz, 6H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 192.3, 170.7, 168.2, 158.9, 145.3, 142.7, 137.7, 132.6, 131.5, 129.9, 129.4, 128.6, 128.4, 113.5, 72.2, 61.8, 61.2, 55.3, 51.0, 40.0, 13.9, 13.7 ppm. HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₃₂H₃₁NO₆, 526.2224; found: 526.2235.

Diethyl 4-benzoyl-5-(2-naphthalen-2-yl-vinyl)-2-phenyl-4,5-dihydropyrrole-3,3-dicarboxylate (7h)

Pale yellow liquid. Yield: 414 mg (76%). ¹H NMR (400 MHz, CDCl₃): δ 7.81–7.60 (m, 11H), 7.49–7.43 (m, 6H), 6.34 (q, J = 7.2 Hz, 1H), 6.15 (q, J = 5.6 Hz, 1H), 5.47 (t, J = 4.4 Hz, 1H), 4.36–4.20 (m, 4H), 3.46 (q, J = 14.8 Hz, 1H), 3.20 (q, J = 11.2 Hz, 1H), 1.31 (t, J = 8.4 Hz, 3H), 0.58 (t, J = 7.2 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 194.0, 173.1, 169.5, 166.8, 153.0, 134.6, 134.0, 131.9, 129.2, 129.1, 129.0, 128.8, 128.6, 128.1, 126.9, 126.4, 126.0, 124.6, 81.6, 62.8, 51.8, 50.8, 14.1, 14.0 ppm. MS (ESI-TOF): m/z 577.23 [M + MeOH]⁺. Anal. calcd for C₃₅H₃₁NO₅: C 77.04, H 5.73, N 2.57; found: C 77.15, H 5.88, N 2.69.

Diethyl 4-benzoyl-2-phenyl-5-(2-thiophen-2-yl-vinyl)-4,5-dihydropyrrole-3,3-dicarboxylate (7i)

Yellow oily liquid. Yield: 361 mg (72%). ¹H NMR (400 MHz, CDCl₃): δ 8.29 (d, J = 8.8 Hz, 3H), 8.05 (d, J = 8.4 Hz, 3H), 7.27–7.19 (m, 8H), 6.56 (d, J = 2.4 Hz, 1H), 5.03–5.01 (m, 1H), 4.27 (q, J = 7.2 Hz, 2H), 3.75–3.70 (m, 2H), 3.57–3.52 (m, 1H), 1.25 (t, J = 7.2 Hz, 3H), 0.77 (t, J = 7.2 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 191.0, 171.8, 167.5, 150.5, 144.8, 143.8, 141.3, 138.0, 130.5, 128.5, 128.4, 127.9, 123.8, 82.0, 72.7, 63.2, 61.7, 60.0, 13.8, 13.4. ppm. HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₂₉H₂₇NO₅S, 502.1683; found: 502.1676.

Diethyl 4-(4-methylbenzoyl)-2-phenyl-5-styryl-4,5-dihydro-pyrrole-3,3-dicarboxylate (7j)

Pale yellow liquid. Yield: 351 mg (69%). ¹H NMR (400 MHz, CDCl₃): δ 8.06 (d, J = 7.2 Hz, 2H), 7.58–7.26 (m, 11H), 6.66–6.57 (m, 2H), 6.21 (q, J = 16.0 Hz, 1H), 4.86 (q, J = 10.0 Hz, 1H), 4.24–4.09 (m, 4H), 2.40 (s, 3H), 1.26 (t, J = 7.2 Hz, 3H), 1.18 (t, J = 7.2 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 191.4, 171.7, 167.6, 144.0, 143.8, 139.8, 134.8, 132.0, 131.0, 129.9, 128.9, 128.6, 128.4, 127.7, 119.2, 109.2, 81.6, 72.3, 62.9, 61.5, 59.9, 21.8, 13.8, 13.5 ppm. MS (ESI-TOF): m/z 542.16 [M + MeOH + H]⁺. Anal. calcd for C₃₂H₃₁NO₅: C 75.42, H 6.13, N 2.75; found: C 75.59, H 6.22, N 2.70.

Diethyl 4-(4-methoxybenzoyl)-2-phenyl-5-styryl-4,5-dihydro-pyrrole-3,3-dicarboxylate (7k)

Yellow oily liquid. Yield: 331 mg (63%). ¹H NMR (400 MHz, CDCl₃): δ 7.95 (d, J = 7.2 Hz, 2H), 7.94–7.37 (m, 5H), 6.89 (d, J = 8.8 Hz, 2H), 6.52 (d, J = 12.0 Hz, 1H), 5.43 (q, J = 8.0 Hz, 1H), 4.24–3.95 (m, 5H), 3.81 (s, 3H), 1.11 (t, J = 7.2 Hz, 3H), 1.03 (t, J = 7.0 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 198.7, 170.0, 169.5, 158.0, 136.4, 135.8, 133.5, 131.3, 130.2, 129.1, 128.6, 113.4, 69.1, 61.4, 61.2, 60.4, 56.0, 55.3, 13.7, 13.4 ppm. HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₃₂H₃₁NO₆, 526.2224; found: 526.2202.

Diethyl-4-(4-nitro-benzoyl)-2-phenyl-5-styryl-4,5-dihydro-pyrrole-3,3-dicarboxylate (7l)

Brown oily liquid. Yield: 367 mg (68%). ¹H NMR (400 MHz, CDCl₃): δ 7.94 (d, J = 7.6 Hz, 2H), 7.51–7.46 (m, 9H), 6.54 (d, J = 16.0 Hz, 1H), 6.44 (d, J = 7.2 Hz, 1H), 5.00 (d, J = 8.0 Hz, 1H), 4.83 (d, J = 7.6 Hz, 1H), 3.96–3.2 (m, 4H), 0.77 (t, J = 7.2 Hz, 3H), 0.63 (t, J = 7.2 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 199.1, 168.7, 168.0, 137.3, 136.9, 136.1, 134.0, 133.8, 130.2, 128.9, 128.7, 128.6, 128.5, 128.7, 128.6, 128.5, 128.1, 127.9, 127.3, 126.9, 126.3, 85.3, 88.0, 70.3, 61.9, 61.5, 57.5, 13.33, 13.25 ppm. MS (ESI-TOF): m/z 579.35 [M + K]⁺. Anal. calcd for C₃₁H₂₈N₂O₇: C 68.88, H 5.22, N 5.18; found: C 68.79, H 5.31, N 5.30.

Diethyl 4-(4-methylbenzoyl)-2-(1-methylene-pent-2-enyl)-5-styryl-4,5-dihydropyrrole-3,3-dicarboxylate (7m)

Yellow oily liquid. Yield: 408 mg (78%). ¹H NMR (400 MHz, CDCl₃): δ 7.72–7.68 (m, 4H), 7.46–7.00 (m, 9H), 6.37 (d, J = 15.6 Hz, 1H), 6.00 (d, J = 7.2 Hz, 1H), 5.34 (t, J = 8.4 Hz, 1H), 5.13 (d, J = 8.4 Hz, 1H), 4.19–4.11 (m, 4H), 2.32 (s, 3H), 2.30 (s, 3H), 1.10 (t, J = 7.2 Hz, 3H), 1.05 (t, J = 7.2 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 195.6, 168.3, 168.1, 167.7, 144.2, 140.6, 136.8, 135.0, 133.8, 132.1, 131.0, 129.9, 129.4, 129.0, 128.51, 128.49, 128.3, 127.5, 129.7, 126.6, 75.0, 73.3, 62.6, 62.1, 59.1, 21.7, 21.5, 13.8, 13.7 ppm. HRMS (ESI-TOF) m/z: [M + NH₄]⁺ calcd for C₃₃H₃₃NO₅, 541.2697; found: 541.2700.

Diethyl 4-benzoyl-2-(4-bromophenyl)-5-(2-p-tolyl-vinyl)-4,5-dihydropyrrole-3,3-dicarboxylate (7n)

Brown liquid. Yield: 355 mg (60%). ¹H NMR (400 MHz, CDCl₃): δ 7.84 (d, J = 8.4 Hz, 2H), 7.44–7.15 (m, 15H), 6.49–6.48 (m, 1H), 4.24–4.09 (m, 3H), 2.31 (s, 3H), 1.18 (t, J = 7.2 Hz, 3H), 0.76 (t, J = 7.2 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 196.8, 168.3, 166.5, 166.4, 143.8, 140.8, 137.2, 136.6, 133.6, 132.0, 129.9, 128.7, 128.6, 128.5, 126.6, 119.2, 109.2, 75.0, 74.7, 62.9, 62.4, 60.3, 21.8, 13.7, 13.6 ppm. HRMS (ESI-TOF) m/z: [M + NH₄]⁺ calcd for C₃₂H₃₀BrNO₅, 605.1646; found: 605.1646.

Diethyl 4-benzoyl-2-methyl-5-(2-p-tolyl-vinyl)-4,5-dihydro-pyrrole-3,3-dicarboxylate (7o)

Pale yellow liquid. Yield: 358 mg (80%). ¹H NMR (400 MHz, CDCl₃): δ 7.76 (d, J = 8.0 Hz, 2H), 7.30–6.99 (m, 7H), 6.49 (d, J = 15.2 Hz, 1H), 5.86 (q, J = 15.2 Hz, 1H), 5.22–5.10 (m, 2H), 4.32–4.10 (m, 4H), 2.49 (s, 3H), 2.36 (s, 3H), 1.31 (t, J = 7.2 Hz, 3H), 1.08 (t, J = 7.0 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 197.2, 166.9, 166.8, 144.1, 136.7, 135.7, 135.2, 133.2, 129.3, 128.6, 128.2, 127.4, 126.7, 126.5, 75.1, 74.2, 62.8, 61.7, 56.8, 21.6, 18.8, 14.0, 13.7 ppm. MS (ESI-TOF): m/z 465.12 [M + NH₄]⁺. Anal. calcd for C₂₇H₂₉NO₅: C 72.46, H 6.53, N 3.13; found: C 72.33, H 6.64, N 3.27.

Diethyl 4-benzoyl-5-[2-(4-nitrophenyl)-vinyl]-2-thiophen-2-yl-4,5-dihydropyrrole-3,3-dicarboxylate (7p)

Yellow oily liquid. Yield: 354 mg (65%). ¹H NMR (400 MHz, CDCl₃): δ 8.01 (d, J = 7.2 Hz, 2H), 7.62–7.38 (m, 5H), 7.14–7.02 (m, 1H), 6.40–6.34 (m, 1H), 5.51– (t, J = 6.8 Hz, 1H), 5.01 (d, J = 6.0 Hz, 1H), 4.31–4.24 (m, 2H), 3.97 (q, J = 7.2 Hz, 2H), 1.21 (t, J = 7.2 Hz, 3H), 1.01 (t, J = 7.2 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 196.5, 167.8, 166.3, 161.0, 147.8, 137.47, 136.8, 133.75, 133.67, 133.14, 132.67, 132.5, 130.8, 129.0, 128.8, 128.6, 128.3, 127.8, 127.7, 127.4, 124.5, 75.0, 74.7, 63.3, 62.4, 59.7, 13.8, 13.5 ppm. HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₂₉H₂₆N₂O₇S, 547.1533; found: 547.1537.

Diethyl 2-methyl-4-(4-methyl-benzoyl)-5-(2-p-tolyl-vinyl)-4,5-dihydropyrrole-3,3-dicarboxylate (7q)

Pale yellow liquid. Yield: 396 mg (86%). ¹H NMR (400 MHz, CDCl₃): δ 7.35 (d, J = 8.0 Hz, 2H), 7.00 (d, J = 8.0 Hz, 3H), 6.90 (d, J = 8.0 Hz, 3H), 6.79 (d, J = 7.6 Hz, 2H), 5.57 (d, J = 6.0 Hz, 1H), 5.34 (d, J = 8.0 Hz, 1H), 4.33–4.02 (m, 4H), 2.58 (s, 3H), 2.31 (s, 3H), 2.12 (s, 3H), 1.33 (t, J = 7.2 Hz, 3H), 0.99 (t, J = 7.2 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 198.3, 169.5, 166.9, 166.7, 143.2, 136.7, 135.4, 134.5, 128.6, 128.3, 128.2, 128.0, 75.7, 75.6, 62.9, 61.5, 57.8, 21.6, 21.0, 18.8, 14.0, 13.6 ppm. MS (ESI-TOF): m/z 494.28 [M + MeOH + H]⁺. Anal. calcd for C₂₈H₃₁NO₅: C 72.86, H 6.77, N 3.03; found: C 72.92, H 6.87, N 3.11.

Synthesis of diethyl 2-[2-benzoylamino-1-(4-methylbenzoyl)-4-phenyl-but-3-enyl]malonate (8)

To a solution of vinyl 1-pyrroline 7b (1.0 mmol, 510 mg) in 1,2-dichloroethane (5 mL) was added SnCl₄ (1.0 mmol, 260 mg). After 15 min, water (1.0 mmol, 18 μL) was added and the reaction mixture was allowed to stir at room temperture for 8 h. After completion of the reaction, the reaction mixture was extracted with dichloromethane. The organic layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. The crude product was purified by column chromatography using EtOAc/hexane (1 : 9) to give 8. Pale yellow liquid. Yield: 400 mg (76%). ¹H NMR (400 MHz, CDCl₃): δ 7.83 (d, J = 8.4 Hz, 2H), 7.44–7.37 (m, 5H), 7.22–7.15 (m, 8H), 6.49 (d, J = 1.6 Hz, 1H), 5.02 (s, J = 1H), 4.24–(m, 3H), 3.74–3.54 (m, 3H), 2.31 (s, 3H), 1.18 (t, J = 7.2 Hz, 3H), 0.76 (t, J = 7.2 Hz, 3H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ 191.4, 171.7, 167.6, 144.0, 143.8, 139.8, 134.8, 132.0, 131.0, 129.9, 128.9, 128.6, 128.4, 127.7, 119.2, 109.2, 72.3, 62.9, 61.5, 59.9, 21.8, 13.8, 13.5 ppm. HRMS (ESI-TOF) m/z: [M + H]⁺ calcd for C₃₂H₃₃NO₆, 528.2381; found: 528.2376.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

The authors thank Science and Engineering Research Board (SERB), India for financial support and DST-FIST for instrumentation facilities at School of Chemistry, Bharathidasan University. M. T. thanks the University Grants Commission (UGC) for a BSR-RFSMS fellowship.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available: Copies of ¹H and ¹³C NMR spectra of all products and X-ray structural information of 8. CCDC 2048692. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/d1ra01194d

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