Efficient synthesis of functionalized spiro[indoline-3,4′-pyridines] and spiro[indene-2,4′-pyridines] via a three-component reaction

Abstract

The three-component reactions of α,β-unsaturated N-arylaldimines, dimethyl acetylenedicarboxylate (methyl propiolate) and isatylidene malononitriles in dry acetonitrile at room temperature afforded polysubstituted spiro[indoline-3,4′-pyridines] in good yields and with high diastereoselectivity. Under similar reaction conditions, the corresponding functionalized spiro[indene-2,4′-pyridines] were also obtained from the three-component reactions containing 2-(1,3-dioxo-1H-inden-2(3H)-ylidene)malononitrile.

---

Introduction

1,4-Dihydropyridines (1,4-DHPs) are well known heterocyclic scaffolds possessing a broad array of biological functions.¹ 1,4-Dihydropyridine derivatives such as felodipine, nicardipine, nifedipine have been frequently used in the treatment of cardiovascular disease and hypertension, as potent calcium channel antagonists, and agonists.^2–5 Besides the valuable pharmaceutical profiles, 1,4-DHPs have also been known as useful building blocks in the synthesis of structurally attractive organic products such as fused and spiro polycyclic molecules.^6–10 In the diverse polycyclic 1,4-DHPs, spiro[indoline-3,4′-pyridine] is now recognized as a privileged heterocyclic scaffold and attracts longlasting interest in organic synthesis, chemical biology and pharmaceutical chemistry.^11–14 Over the last decade, multicomponent reactions have witnessed a burgeoning progress due to their privileged reaction efficiency, operation simplicity and molecular diversity.^15,16 Practically, Nair¹⁷ and Shi¹⁸ reported that the cycloaddition reaction of Huisgen 1,4-dipoles generated from N-heterocyclic arenes and acetylenedicarboxylates with isatylidene malonitriles afforded spiro[indoline-3,2′-quinolizines] or spiro[indoline-3,2′-pyrido[2,1-a]isoquinolines] (eqn (1) in Scheme 1). Perumal¹⁹ and we²⁰ successfully found that the in situ generated 1,3-dipoles from addition of arylamines to acetylenedicarboxylates also reacted with isatylidene malonitriles to give the corresponding spiro[indoline-3,4′-pyridine] derivatives (eqn (2) in Scheme 1). On the other hand, N-arylaldimines and its α,β-unsaturated derivatives reacted with dialkyl acetylenedicarboxylates to give analogous 1,4-dipoles, which were in turn strapped by carbonyl compounds such as aldehydes and isatins to give 1,3-oxazine derivatives.^21,22 This interesting results showed that the 1,4-dipoles derived from reaction of N-arylaldimines and acetylenedicarboxylates have comparable reactivity to that of Huisgen 1,4-dipoles. In order to exploit the synthetic applications of the 1,4-dipoles derived from N-arylaldimines and acetylenedicarboxylates, herein we wish to report the three-component reaction of α,β-unsaturated N-arylaldimines, dialkyl acetylenedicarboxylates and isatylidene malononitrile and its derivatives for the convenient synthesis of polyfunctionalized spiro[indoline-3,4′-pyridines] (eqn (3) in Scheme 1).

Scheme 1 Construction of spiro[indoline-3,4′-pyridine] via different reactions of isatylidene malononitrile.

Results and discussions

According to the previously established reaction procedure of three-component reaction of N-arylaldimines, acetylenedicarboxylates and isatins for the synthesis of spiro[indoline-3,6′-[1,3]oxazines],^22a the three-component reaction of α,β-unsaturated N-arylaldimine, dimethyl acetylenedicarboxylate and isatylidene malononitriles was carried out in dry acetonitrile at room temperature. After workup, the expected polysubstituted 2′,3′-dihydro-1′H-spiro[indoline-3,4′-pyridines] 3a–3m were obtained in good yields (Table 1). The substituents on the substrates showed very little effect to the yields of the products. The structures of the obtained spiro[indoline-3,4′-pyridines] 3a–3m were fully characterized by IR, HRMS, ¹H and ¹³C NMR spectra. Because the 2′-stylyl group and the phenyl group of oxindole moiety can exist in cis/trans-positions in the newly-formed dihyropyridyl ring, the obtained products 3a–3m might have cis/trans-configurations. ¹H and ¹³C NMR spectra of the compounds 3a–3m usually showed one set of absorptions for the characterized group in the molecules except the products 3g and 3l, in which a mixture of two diastereoisomers were obtained in a ratio of 1 : 1 and 1 : 9. This result indicated that one diastereoisomer usually exist predominately in the products 3a–3m. The single crystal structure of the product 3i was successfully determined by X-ray diffraction method (Fig. 1). From Fig. 1 it can be seen that the styryl group exists in the trans-position to the phenyl group of oxindole moiety. On the basis of ¹H NMR spectra and single crystal structure, we confessedly assigned the obtained products 3a–3m has the trans-configuration except compounds 3g and 3l. Then, the single crystal obtained from the product 3g containing a mixture of cis/trans-isomers also successfully determined by X-ray diffraction (Fig. 1). In the molecular structure showed in Fig. 1, the styryl group exists in the cis-position to the phenyl group of oxindole moiety. Thus, it is a cis-isomer. It should be pointed out that the similar three-component reaction of α,β-unsaturated N-arylaldimines, dimethyl acetylenedicarboxylates and isatins usually resulted in the spiro[indoline-3,6′-[1,3]oxazines] in a mixture of cis/trans-diastereoisomers.²² Thus, this three-component reaction had high diastereoselectivity and afforded polysubstituted spiro[indoline-3,4′-pyridines] mainly in the trans-diastereoisomer.

Table 1 Synthesis of spiro[indoline-3,4′-pyridines] 3a–3m^a

Entry	Compd	Ar	Ar′	R^1	R^2	Yield^b (%, ratio of cis/trans-isomer)
a Reaction conditions: α,β-unsaturated N-arylaldimines (1.0 mmol), dimethyl acetylenedicarboxylate (1.0 mmol) and isatylidene malononitrile (1.0 mmol), in CH3CN (15.0 mL), rt, 24 h. b Isolated yields.
1	3a	Ph	p-MeOC6H4	H	Bn	80
2	3b	Ph	p-MeOC6H4	H	n-Pr	79
3	3c	Ph	p-MeOC6H4	F	n-Bu	75
4	3d	Ph	p-MeOC6H4	Cl	n-Pr	78
5	3e	m-ClC6H4	Ph	H	n-Pr	72
6	3f	m-ClC6H4	Ph	F	Bn	75
7	3g	m-ClC6H4	Ph	Cl	n-Pr	70 (1 : 1)
8	3h	m-ClC6H4	p-BrC6H4	H	n-Pr	81
9	3i	m-ClC6H4	p-BrC6H4	H	Bn	77
10	3j	m-ClC6H4	p-BrC6H4	F	Bn	76
11	3k	m-ClC6H4	p-BrC6H4	F	n-Bu	76
12	3l	m-ClC6H4	p-BrC6H4	Cl	n-Pr	79 (1 : 9)
13	3m	p-NO2C6H4	p-MeOC6H4	H	Bn	74

---

Fig. 1 Molecular structure of compound 3i (trans-isomer) and 3g (cis-isomer).

In order to develop the scope of this reaction, another common electron-deficient alkyne, methyl propiolate, was also employed in the three-component reaction. The results are summarized in Table 2. It can be seen that all reactions proceeded very smoothly to give the expected spiro[indoline-3,4′-pyridines] 4a–4g in good yields. The structures of the obtained compounds 4a–4g were established on IR, HRMS, ¹H and ¹³C NMR spectroscopy. The ¹H NMR of clearly indicated that only one diastereoisomer existed in the obtained examples of the products 4a–4g. The single crystal structure of the compound 4c was determined by X-ray diffraction method (Fig. 2). The styryl group and the phenyl group of oxindole moiety actually exist in the same side of the newly-formed dihydropyridyl ring in the molecule. Thus, it has same configuration with that of cis-diastereoisomer of compound 3g. According to the ¹H NMR data and single crystal structure, all prepared products 4a–4g have the cis-configuration.

Table 2 Synthesis of spiro[indoline-3,4′-pyridines] 4a–4g^a

Entry	Compd	Ar	Ar′	R^1	R^2	Yield^b [%]
a Reaction conditions: α,β-unsaturated N-arylaldimines (1.0 mmol), methyl propiolate (1.0 mmol) and isatylidene malononitrile (1.0 mmol), in CH3CN (15.0 mL), rt, 24 h. b Isolated yields.
1	4a	Ph	p-ClC6H4	H	Bn	78
2	4b	Ph	p-BrC6H4	H	Bn	82
3	4c	Ph	p-MeOC6H4	CH3	Bn	73
4	4d	Ph	p-MeOC6H4	CH3	n-Bu	68
5	4e	Ph	p-MeC6H4	F	n-Pr	69
6	4f	Ph	p-MeC6H4	F	Bn	64
7	4g	m-MeC6H4	p-MeC6H4	Cl	Bn	79

---

Fig. 2 Molecular structure of compound 4c (cis-isomer).

Encouraged by this result, this new methodology was then applied to 2-(1,3-dioxo-1H-inden-2(3H)-ylidene)malononitrile. Under similar reaction conditions, the three-component reaction of α,β-unsaturated N-arylaldimine, dimethyl acetylenedicarboxylate and 2-(1,3-dioxo-1H-inden-2(3H)-ylidene)malononitrile in dry acetonitrile at room temperature afforded the expected functionalized spiro[indene-2,4′-pyridines] 5a–5g in high yields (Table 3). Because the scaffold of indan-1,3-dione is symmetric, there are no diastereoisomers existing in the prepared functionalized spiro[indene-2,4′-pyridines]. The elucidation of the structures of the compounds becomes much simple. The single crystal structure of the compound 5d was also determined by X-ray diffraction method (Fig. 3).

Table 3 Synthesis of spiro[indene-2,4′-pyridines] 5a–5g^a

Entry	Compd	Ar	Ar′	Yield^b (%)
a Reaction conditions: α,β-unsaturated N-arylaldimines (1.0 mmol), dimethyl acetylenedicarboxylate (1.0 mmol) and 2-(1,3-dioxo-1H-inden-2(3H)-ylidene)malononitrile (1.0 mmol), in CH3CN (15.0 mL), rt, 24 h. b Isolated yields.
1	5a	Ph	Ph	72
2	5b	Ph	p-MeC6H4	78
3	5c	Ph	p-MeOC6H4	80
4	5d	m-MeC6H4	Ph	70
5	5e	m-MeC6H4	p-MeOC6H4	75
6	5f	m-MeC6H4	p-BrC6H4	68

---

Fig. 3 Molecular structure of compound 5d.

This three-component reaction proceeded very straightly. A concise reaction mechanism was proposed on the basis of the previously reported domino reactions containing of N-arylaldimine and electron-deficient alkynes (Scheme 2).²¹ The nucleophilic addition of α,β-unsaturated N-arylaldimines to dimethyl acetylenedicarboxylate resulted in the desired reactive intermediate (A). Then, Michael addition of carbanium ion of intermediate (A) to isatylidene malononitrile afforded a zwitterionic adduct (B). Finally, the intramolecular coupling of positive iminium ion with negative carbanium ion produced spiro[indoline-3,4′-pyridines] 3. Apparently, both cis-isomer and trans-isomer of spiro[indoline-3,4′-pyridines] could be formed in the final cyclization process. It might be pointed out that each reaction step in above sequential reaction process are in retro-equilibrium, the most stable stereoisomer should be formed as main product.

Scheme 2 Proposed reaction mechanism for three-component reaction.

In summary, we have successfully provided an convenient synthetic protocol for the preparation of functionalized spiro[indoline-3,4′-pyridines] by the three-component reaction of α,β-unsaturated N-arylaldimines, acetylenedicarboxylates and isatylidene malononitrile. This reaction developed further applications of the reactive 1,4-dipolar intermediates in the synthesis of diverse heterocycles. The advantages of this reaction included using readily variable substrates, milder reaction conditions, easiness of handling, satisfactory yields and high diastereoselectivity. Further expansion of the reaction scope and synthetic applications of this methodology is underway.

Experimental section

General procedure for the synthesis of spiro[indoline-3,4′-pyridines] 3a–3m and 4a–4g from three-component reaction

A mixture of α,β-unsaturated N-arylaldimine (1.0 mmol), dimethyl acetylenedicarboxylate or methyl propiolate (1.0 mmol) and isatylidene malononitrile (1.0 mmol) in dry acetonitrile (15.0 mL) was stirred at room temperature for about 24 hours. After removing the solvent, the resulting oily residue was subjected to thin-layer chromatography with light petroleum and ethyl acetate (V/V = 2.5 : 1) as eluting solvent to give the pure product for analysis.

Dimethyl 1-benzyl-3′,3′-dicyano-1′-(4-methoxyphenyl)-2-oxo-2′-styryl-2′,3′-dihydro-1′H-spiro[indoline-3,4′-pyridine]-5′,6′-dicarboxylate (3a). White solid, 80%, m.p. 168–170 °C; ¹H NMR (400 MHz, CDCl₃) δ: 7.63 (d, J = 7.0 Hz, 1H, ArH), 7.44 (d, J = 7.1 Hz, 2H, ArH), 7.39–7.26 (m, 6H, ArH), 7.25 (s, 1H, ArH), 7.21–7.18 (m, 1H, ArH), 7.13 (t, J = 7.3 Hz, 1H, ArH), 6.87–6.78 (m, 4H, ArH, CH), 5.90 (dd, J = 15.5, 9.9 Hz, 1H, CH), 5.78 (d, J = 9.9 Hz, 1H, CH), 5.26 (d, J = 15.6 Hz, 1H, CH), 4.86 (d, J = 15.7 Hz, 1H, CH), 3.77 (s, 3H, OCH₃), 3.50 (s, 3H, OCH₃), 3.13 (s, 3H, OCH₃); ¹³C NMR (100 MHz, CDCl₃) δ: 174.5, 164.1, 163.1, 159.7, 151.5, 143.2, 140.7, 135.0, 134.7, 131.4, 130.3, 129.1, 128.8, 128.7, 127.9, 127.6, 127.1, 126.4, 124.2, 123.6, 119.3, 111.7, 111.1, 110.0, 94.1, 60.9, 55.4, 52.5, 52.0, 51.3, 46.0, 45.0, 29.7; IR (KBr) ν: 3033, 2997, 2952, 2916, 2836, 1895, 1745, 1711, 1654, 1606, 1572, 1508, 1488, 1468, 1433, 1363, 1301, 1268, 1250, 1217, 1170, 1146, 1112, 1079, 1031, 961, 925, 835, 795, 748, 700 cm⁻¹; MS (m/z): HRMS (ESI) calcd for C₄₀H₃₂N₄NaO₆ ([M + Na]⁺): 687.2214, found: 687.2208.

Dimethyl 3′,3′-dicyano-1′-(4-methoxyphenyl)-2-oxo-1-propyl-2′-styryl-2′,3′-dihydro-1′H-spiro[indoline-3,4′-pyridine]-5′,6′-dicarboxylate (3b). White solid, 79%, m.p. 170–172 °C; ¹H NMR (400 MHz, CDCl₃) δ: 7.63 (d, J = 7.5 Hz, 1H, ArH), 7.41 (d, J = 7.7 Hz, 1H, ArH), 7.29–7.23 (m, 4H, ArH), 7.19–7.13 (m, 3H, ArH), 6.99 (d, J = 7.8 Hz, 1H, ArH), 6.83–6.76 (m, 3H, ArH, CH), 5.92–5.86 (m, 1H, CH), 5.74 (d, J = 9.9 Hz, 1H, CH), 3.86–3.75 (m, 5H, CH₂, OCH₃), 3.48 (s, 3H, OCH₃), 3.27 (s, 3H, OCH₃), 1.84–1.79 (m, 2H, CH₂), 1.06 (t, J = 7.4 Hz, 3H, CH₃); ¹³C NMR (100 MHz, CDCl₃) δ: 174.2, 164.1, 163.2, 159.7, 151.4, 143.6, 140.5, 134.8, 131.5, 130.3, 129.1, 128.6, 127.1, 126.5, 124.3, 123.3, 119.3, 111.7, 110.9, 109.1, 94.3, 60.8, 55.4, 52.5, 51.7, 51.3, 45.9, 42.8, 20.7, 11.5; IR (KBr) ν: 3056, 3023, 2952, 2877, 2841, 1745, 1718, 1698, 1609, 1585, 1508, 1489, 1467, 1438, 1387, 1361, 1336, 1301, 1248, 1224, 1201, 1141, 1109, 1072, 1035, 981, 964, 932, 866, 848, 796, 759 cm⁻¹; MS (m/z): HRMS (ESI) calcd for C₃₆H₃₂N₄NaO₆ ([M + Na]⁺): 639.2214, found: 639.2222.

Dimethyl 1-butyl-3′,3′-dicyano-5-fluoro-1′-(4-methoxyphenyl)-2-oxo-2′-styryl-2′,3′-dihydro-1′H-spiro[indoline-3,4′-pyridine]-5′,6′-dicarboxylate (3c). White solid, 75%, m.p. 240–242 °C; ¹H NMR (400 MHz, CDCl₃) δ: 7.29 (s, 1H, ArH), 7.27–7.08 (m, 8H, ArH), 6.94–6.91 (m, 1H, ArH), 6.81 (d, J = 7.8 Hz, 2H, ArH), 6.67 (d, J = 15.6 Hz, 1H, CH), 6.01 (s, 1H, CH), 4.85 (d, J = 9.4 Hz, 1H, CH), 3.87 (dd, J = 14.4, 7.3 Hz, 1H, CH), 3.80 (d, J = 7.5 Hz, 1H, CH), 3.76 (s, 3H, OCH₃), 3.52 (s, 3H, OCH₃), 3.47 (s, 3H, OCH₃), 1.73–1.71 (m, 2H, CH₂), 1.52–1.46 (m, 2H, CH₂), 0.99 (t, J = 7.3 Hz, 3H, CH₃); ¹³C NMR (100 MHz, CDCl₃) δ: 172.3, 163.7, 163.2, 160.0, 159.7, 157.6, 150.7, 140.5, 140.3, 134.5, 131.5, 131.2, 130.1, 130.0, 129.3, 128.7, 127.1, 119.0, 117.1 (d, J = 23.1 Hz), 114.1, 113.5 (d, J = 25.3 Hz), 110.6, 110.4, 110.0, 109.6 (d, J = 5.1 Hz), 93.7, 55.4, 52.6, 51.8, 45.1, 40.9, 29.1, 20.3, 13.7; IR (KBr) ν: 3069, 3006, 2955, 2872, 2552, 2297, 1721, 1688, 1651, 1607, 1527, 1510, 1492, 1439, 1387, 1344, 1285, 1250, 1226, 1176, 1148, 1111, 1084, 1023, 972, 931, 891, 855, 821, 798, 761, 724 cm⁻¹; MS (m/z): HRMS (ESI) calcd for C₃₇H₃₃FN₄NaO₆ ([M + Na]⁺): 671.2276, found: 671.2290.

Dimethyl 5-chloro-3′,3′-dicyano-1′-(4-methoxyphenyl)-2-oxo-1-propyl-2′-styryl-2′,3′-dihydro-1′H-spiro[indoline-3,4′-pyridine]-5′,6′-dicarboxylate (3d). White solid, 78%, m.p. 200–202 °C; ¹H NMR (400 MHz, CDCl₃) δ: 7.62 (d, J = 1.9 Hz, 1H, ArH), 7.41–7.38 (m, 1H, ArH), 7.27–7.26 (s, 4H, ArH), 7.19–7.17 (m, 3H, ArH), 6.92 (d, J = 8.4 Hz, 1H, ArH), 6.85–6.77 (m, 3H, ArH, CH), 5.86 (dd, J = 15.5, 9.9 Hz, 1H, CH), 5.72 (d, J = 9.9 Hz, 1H, CH), 3.86–3.79 (m, 1H, CH), 3.77 (s, 3H, OCH₃), 3.75–3.69 (m, 1H, CH), 3.50 (s, 3H, OCH₃), 3.34 (s, 3H, OCH₃), 1.82–1.77 (m, 2H, CH₂), 1.05 (t, J = 7.4 Hz, 3H, CH₃); ¹³C NMR (100 MHz, CDCl₃) δ: 173.8, 163.8, 163.0, 159.7, 151.7, 142.3, 140.8, 134.6, 131.2, 130.4, 129.2, 128.8, 128.7, 128.2, 127.1, 124.7, 119.0, 111.5, 110.6, 110.0, 93.6, 60.9, 55.4, 52.5, 51.8, 51.6, 45.7, 43.0, 29.7, 20.6, 11.5; IR (KBr) ν: 3025, 2952, 2878, 2839, 1746, 1703, 1652, 1607, 1573, 1509, 1486, 1434, 1381, 1340, 1300, 1250, 1220, 1202, 1140, 1108, 1030, 968, 915, 891, 833, 759, 727 cm⁻¹; MS (m/z): HRMS (ESI) calcd for C₃₃H₃₁ClN₄NaO₆ ([M + Na]⁺): 673.1824, found: 673.1830.

Dimethyl 2′-(3-chlorostyryl)-3′,3′-dicyano-2-oxo-1′-phenyl-1-propyl-2′,3′-dihydro-1′H-spiro[indoline-3,4′-pyridine]-5′,6′-dicarboxylate (3e). White solid, 72%, m.p. 170–172 °C; ¹H NMR (400 MHz, CDCl₃) δ: 7.63 (d, J = 7.6 Hz, 1H, ArH), 7.45–7.33 (m, 6H, ArH), 7.23–7.14 (m, 3H, ArH), 7.10 (s, 1H, ArH), 7.00 (t, J = 6.5 Hz, 2H, ArH), 6.72 (d, J = 15.4 Hz, 1H, CH), 5.88 (dd, J = 15.3, 9.9 Hz, 1H, CH), 5.77 (d, J = 10.0 Hz, 1H, CH), 3.87–3.74 (m, 2H, CH₂), 3.45 (s, 3H, OCH₃), 3.28 (s, 3H, OCH₃), 1.82 (dd, J = 14.8, 7.3 Hz, 2H, CH₂), 1.06 (t, J = 7.4 Hz, 3H, CH₃); ¹³C NMR (100 MHz, CDCl₃) δ: 174.0, 164.0, 163.0, 150.8, 143.6, 139.3, 138.9, 136.4, 134.6, 130.5, 130.4, 129.9, 129.3, 129.1 (2C), 126.9, 126.3, 125.2, 124.3, 123.4, 120.9, 111.6, 110.8, 109.2, 94.8, 60.5, 52.5, 51.6, 51.4, 45.8, 42.9, 20.5, 11.5; IR (KBr) ν: 3059, 3023, 2967, 2948, 2876, 1751, 1715, 1609, 1587, 1489, 1466, 1435, 1355, 1303, 1273, 1243, 1215, 1138, 1093, 1072, 980, 940, 892, 863, 829, 787, 754 cm⁻¹; MS (m/z): HRMS (ESI) calcd for C₃₅H₂₉ClN₄NaO₅ ([M + Na]⁺): 643.1719, found: 643.1726.

Dimethyl 1-benzyl-2′-(3-chlorostyryl)-3′,3′-dicyano-5-fluoro-2-oxo-1′-phenyl-2′,3′-dihydro-1′H-spiro[indoline-3,4′-pyridine]-5′,6′-dicarboxylate (3f). White solid, 75%, m.p. 228–230 °C; ¹H NMR (400 MHz, CDCl₃) δ: 7.43–7.29 (m, 11H, ArH), 7.24–7.17 (m, 2H, ArH), 7.12 (s, 1H, ArH), 7.01–7.00 (m, 2H, ArH), 6.80–6.74 (m, 2H, ArH, CH), 5.91–5.80 (m, 2H, CH, CH), 5.24 (d, J = 15.7 Hz, 1H, CH), 4.85 (d, J = 15.7 Hz, 1H, CH), 3.47 (s, 3H, OCH₃), 3.22 (s, 3H, OCH₃); ¹³C NMR (100 MHz, CDCl₃) δ: 174.2, 163.8, 162.8, 160.6, 158.2, 151.3, 139.1, 139.3 (2C), 138.6, 136.3, 134.7, 134.6, 130.4, 129.9, 129.5, 129.2, 129.1, 128.9, 128.1, 127.9 (2C), 127.5, 127.0, 125.1, 120.6, 116.8 (d, J = 23.4 Hz), 116.1, 112.6 (d, J = 25.4 Hz), 111.3, 110.8 (d, J = 4.5 Hz), 110.7, 94.0, 60.6, 52.5, 51.6, 45.6, 45.2; IR (KBr) ν: 3065, 3031, 2952, 1747, 1716, 1652, 1581, 1491, 1451, 1434, 1378, 1351, 1306, 1266, 1220, 1179, 1139, 1068, 1024, 978, 932, 885, 826, 779, 726 cm⁻¹; MS (m/z): HRMS (ESI) calcd for C₃₉H₂₈ClFN₄NaO₅ ([M + Na]⁺): 709.1624, found: 709.1626.

Dimethyl 5-chloro-2′-(3-chlorostyryl)-3′,3′-dicyano-2-oxo-1′-phenyl-1-propyl-2′,3′-dihydro-1′H-spiro[indoline-3,4′-pyridine]-5′,6′-dicarboxylate (3g). White solid, 70%, m.p. 220–222 °C; ¹H NMR (400 MHz, CDCl₃) trans-isomer: δ: 7.67–7.63 (m, 1H, ArH), 7.49–7.34 (m, 6H, ArH), 7.23–7.14 (m, 2H, ArH), 7.10 (s, 1H, ArH), 7.02–7.69 (m, 1H, ArH), 6.93 (d, J = 8.4 Hz, 1H, ArH), 6.70 (d, J = 5.2 Hz, 1H, CH), 5.85–5.81 (m, 1H, CH), 5.79–5.75 (m, 1H, CH), 3.85–3.74 (m, 2H, CH₂), 3.46 (s, 3H, OCH₃), 3.45 (s, 3H, OCH₃), 1.87–1.77 (m, 2H, CH₂), 1.06 (t, J = 7.4 Hz, 3H, CH₃); cis-isomer: 7.23–7.14 (m, 1H, ArH), 7.02–7.69 (m, 1H, ArH), 6.75 (d, J = 5.2 Hz, 1H, CH), 5.91–5.87 (m, 1H, CH), 3.45 (s, 3H, OCH₃), 3.28 (s, 3H, OCH₃), 1.08–1.06 (m, 3H, CH₃); ratio of cis/trans isomer = 1 : 1; ¹³C NMR (100 MHz, CDCl₃) δ: 173.7, 163.7, 162.8, 151.1, 142.3, 139.5, 138.6, 136.3, 134.7, 130.5, 130.3, 129.9, 129.2, 129.2, 129.1, 128.9, 128.0, 127.0, 125.2, 124.7, 120.6, 111.3, 110.5, 110.1, 94.2, 60.5, 52.5, 51.7, 51.6, 45.6, 43.0, 20.6, 11.5; IR (KBr) ν: 3059, 3024, 2968, 2930, 2876, 1750, 1716, 1609, 1587, 1483, 1434, 1387, 1346, 1303, 1261, 1243, 1216, 1139, 1110, 1077, 1024, 983, 892, 828, 785, 732 cm⁻¹; MS (m/z): HRMS (ESI) calcd for C₃₅H₂₈Cl₂N₄NaO₅ ([M + Na]⁺): 677.1329, found: 677.1329.

Dimethyl 1′-(4-bromophenyl)-2′-(3-chlorostyryl)-3′,3′-dicyano-2-oxo-1-propyl-2′,3′-dihydro-1′H-spiro[indoline-3,4′-pyridine]-5′,6′-dicarboxylate (3h). White solid, 81%, m.p. 196–198 °C; ¹H NMR (400 MHz, CDCl₃) δ: 7.61 (d, J = 7.6 Hz, 1H, ArH), 7.49 (d, J = 8.1 Hz, 2H, ArH), 7.43 (t, J = 7.8 Hz, 1H, ArH), 7.26 (s, 1H, ArH), 7.24–7.15 (m, 5H, ArH), 7.06 (d, J = 7.4 Hz, 1H, ArH), 7.00 (d, J = 7.9 Hz, 1H, ArH), 6.74 (d, J = 15.4 Hz, 1H, CH), 5.90–5.84 (m, 1H, CH), 5.74 (d, J = 9.9 Hz, 1H, CH), 3.85–3.75 (m, 2H, CH₂), 3.50 (s, 3H, OCH₃), 3.28 (s, 3H, OCH₃), 1.81–1.77 (m, 2H, CH₂), 1.05 (t, J = 7.3 Hz, 3H, CH₃); ¹³C NMR (100 MHz, CDCl₃) δ: 173.9, 163.8, 162.9, 150.3, 143.6, 139.8, 138.0, 136.1, 134.8, 132.4, 131.9, 130.6, 130.1, 129.4, 127.0, 126.1, 125.2, 124.3, 123.5, 120.4, 111.5, 110.6, 109.3, 95.9, 60.5, 52.7, 51.6, 51.5, 45.8, 42.9, 20.7, 11.5; IR (KBr) ν: 3028, 2968, 2875, 1740, 1718, 1694, 1612, 1579, 1489, 1469, 1473, 1383, 1364, 1332, 1268, 1224, 1201, 1142, 1098, 14 071, 1050, 1012, 966, 933, 899, 863, 835, 797, 771, 745, 714 cm⁻¹; MS (m/z): HRMS (ESI) calcd for C₃₅H₂₈BrClN₄NaO₅ ([M + Na]⁺): 721.0824, found: 721.0826.

Dimethyl 1-benzyl-1′-(4-bromophenyl)-2′-(3-chlorostyryl)-3′,3′-dicyano-2-oxo-2′,3′-dihydro-1′H-spiro[indoline-3,4′-pyridine]-5′,6′-dicarboxylate (3i). White solid, 77%, m.p. 204–206 °C; ¹H NMR (400 MHz, CDCl₃) δ: 7.51–7.49 (m, 4H, ArH), 7.43–7.26 (m, 7H, ArH), 7.25–7.16 (m, 4H, ArH), 7.06 (d, J = 7.3 Hz, 1H, ArH), 6.93 (d, J = 7.8 Hz, 1H, ArH), 6.62 (d, J = 15.7 Hz, 1H, CH), 6.05 (s, 1H, CH), 5.11 (d, J = 15.6 Hz, 1H, CH), 5.01 (d, J = 15.6 Hz, 1H, CH), 4.93 (d, J = 9.4 Hz, 1H, CH), 3.54 (s, 3H, OCH₃), 3.29 (s, 3H, OCH₃); ¹³C NMR (100 MHz, CDCl₃) δ: 172.6, 163.6, 163.1, 149.5, 143.8, 139.5, 135.9, 135.1, 134.8, 132.5, 131.7, 131.1, 130.1, 129.5, 128.8, 128.1 (2C), 127.9, 127.2, 125.1, 125.0, 123.6, 123.1, 120.3, 110.5, 110.1, 95.7, 52.8, 51.9, 45.3, 45.0; IR (KBr) ν: 3059, 3006, 2950, 1716, 1686, 1591, 1487, 1434, 1362, 1339, 1290, 1216, 1187, 1145, 1102, 1069, 1011, 970, 940, 872, 786, 752, 735 cm⁻¹; MS (m/z): HRMS (ESI) calcd for C₃₉H₂₈BrC N₄NaO₅ ([M + Na]⁺): 769.0824, found: 769.0825.

Dimethyl 1-benzyl-1′-(4-bromophenyl)-2′-(3-chlorostyryl)-3′,3′-dicyano-5-fluoro-2-oxo-2′,3′-dihydro-1′H-spiro[indoline-3,4′-pyridine]-5′,6′-dicarboxylate (3j). White solid, 76%, m.p. 238–240 °C; ¹H NMR (400 MHz, CDCl₃) δ: 7.48 (d, J = 7.6 Hz, 4H, ArH), 7.27–7.28 (m, 5H, ArH), 7.24–7.18 (m, 3H, ArH), 7.10–7.07 (m, 3H, ArH), 6.85–6.82 (m, 1H, ArH), 6.67 (d, J = 15.6 Hz, 1H, CH), 6.04 (brs, 1H, CH), 5.09 (d, J = 15.6 Hz, 1H, CH), 5.00 (d, J = 16.0 Hz, 1H, CH), 4.84 (d, J = 9.4 Hz, 1H, CH), 3.56 (s, 3H, OCH₃), 3.34 (s, 3H, OCH₃); ¹³C NMR (100 MHz, CDCl₃) δ: 172.3, 163.6, 163.1, 160.1, 157.7, 149.8, 139.9, 135.9, 134.8 (2C), 132.4, 131.7, 130.1, 129.5, 128.9, 128.0, 127.9, 127.2, 125.2, 123.7, 120.0, 117.4 (d, J = 23.7 Hz), 113.4 (d, J = 25.4 Hz), 110.8 (d, J = 7.2 Hz), 110.3, 52.9, 52.0, 45.2, 45.1; IR (KBr) ν: 3071, 3031, 2953, 2853, 1867, 1726, 1691, 1650, 1572, 1490, 1438, 1384, 1340, 1292, 1246, 1226, 1180, 1146, 1101, 1073, 1014, 966, 891, 820, 737 cm⁻¹; MS (m/z): HRMS (ESI) calcd for C₃₉H₂₇BrClFN₄NaO₅ ([M + Na]⁺): 787.0730, found: 787.0726.

Dimethyl 1′-(4-bromophenyl)-1-butyl-2′-(3-chlorostyryl)-3′,3′-dicyano-5-fluoro-2-oxo-2′,3′-dihydro-1′H-spiro[indoline-3,4′-pyridine]-5′,6′-dicarboxylate (3k). White solid, 76%, m.p. 204–206 °C; ¹H NMR (400 MHz, CDCl₃) δ: 7.50 (d, J = 8.4 Hz, 2H, ArH), 7.39 (dd, J = 7.8, 2.4 Hz, 1H, ArH), 7.26 (d, J = 3.5 Hz, 1H, ArH), 7.25–7.18 (m, 3H, ArH), 7.18–7.12 (m, 2H, ArH), 7.06 (d, J = 7.4 Hz, 1H, ArH), 6.95–6.92 (m, 1H, ArH), 6.75 (d, J = 15.4 Hz, 1H, CH), 5.85 (dd, J = 15.4, 9.9 Hz, 1H, CH), 5.74 (d, J = 9.9 Hz, 1H, CH), 3.82 (dd, J = 8.4, 6.2 Hz, 2H, CH₂), 3.51 (s, 3H, OCH₃), 3.34 (s, 3H, OCH₃), 1.75 (dd, J = 14.9, 7.5 Hz, 2H, CH₂), 1.47 (dd, J = 15.0, 7.5 Hz, 2H, CH₂), 0.99 (t, J = 7.3 Hz, 3H, CH₃); ¹³C NMR (100 MHz, CDCl₃) δ: 173.6, 163.6, 162.7, 160.5, 158.0, 150.6, 140.0, 139.6 (2C), 137.8, 136.0, 134.8, 132.4, 131.9, 130.0, 129.4, 127.8, 127.7, 127.1, 125.2, 123.6, 120.1, 117.1, 116.9 (d, J = 23.3 Hz), 112.7 (d, J = 24.9 Hz), 112.5, 111.3, 110.4, 109.9 (d, J = 7.9 Hz), 109.8, 95.2, 60.5, 52.7, 51.8, 51.7, 45.6, 41.1, 29.1, 20.2, 13.7; IR (KBr) ν: 3067, 2951, 2926, 2873, 1746, 1711, 1616, 1569, 1491, 1435, 1406, 1378, 1351, 1305, 1267, 1226, 1170, 1139, 1103, 1073, 1046, 1012, 989, 932, 866, 818, 716 cm⁻¹; MS (m/z): HRMS (ESI) calcd for C₃₆H₂₉BrClFN₄NaO₅ ([M + Na]⁺): 753.0886, found: 753.0880.

Dimethyl 1′-(4-bromophenyl)-5-chloro-2′-(3-chlorostyryl)-3′,3′-dicyano-2-oxo-1-propyl-2′,3′-dihydro-1′H-spiro[indoline-3,4′-pyridine]-5′,6′-dicarboxylate (3l). White solid, 79%, m.p. 210–212 °C; ¹H NMR (400 MHz, CDCl₃) trans-isomer δ: 7.60 (s, 1H, ArH), 7.52–7.49 (m, 2H, ArH), 7.43–7.40 (m, 1H, ArH), 7.23–7.12 (m, 6H, ArH), 7.06 (d, J = 7.4 Hz, 1H, ArH), 6.93 (d, J = 8.3 Hz, 1H, ArH), 6.75 (d, J = 15.4 Hz, 1H, CH), 5.87–5.80 (m, 1H, CH), 5.72 (d, J = 10.0 Hz, 1H, CH), 3.82–3.73 (m, 2H, CH₂), 3.51 (s, 3H, OCH₃), 3.35 (s, 3H, OCH₃), 1.84–1.75 (m, 2H, CH₂), 1.04 (t, J = 7.4 Hz, 3H, CH₃); cis-isomer: 7.96 (s, 1H, ArH), 6.87 (d, J = 8.0 Hz, 1H, ArH), 6.45 (d, J = 15.2 Hz, 1H, CH), 6.11–6.05 (m, 1H, CH), 3.67 (s, 3H, OCH₃), 3.49 (s, 3H, OCH₃), 0.93 (t, J = 7.3 Hz, 3H, CH₃). Ratio of cis/trans isomer = 1 : 9. ¹³C NMR (100 MHz, CDCl₃) δ: 173.5, 163.6, 162.7, 150.6, 142.3, 140.0, 137.8, 136.0, 134.8, 132.4, 131.9, 130.6, 130.0, 129.5, 128.9, 127.8, 127.1, 125.2, 124.7, 123.6, 120.1, 111.2, 110.3, 110.2, 95.2, 60.6, 52.7, 51.8, 51.7, 45.6, 43.0, 20.6, 11.5; IR (KBr) ν: 3089, 3060, 2954, 2874, 1743, 1721, 1695, 1645, 1612, 1576, 1488, 1431, 1405, 1385, 1352, 1305, 1267, 1223, 1143, 1107, 1072, 1048, 1011, 968, 934, 888, 836, 795, 773, 711 cm⁻¹; MS (m/z): HRMS (ESI) calcd for C₃₅H₂₇BrCl₂N₄NaO₅ ([M + Na]⁺): 755.0434, found: 755.0428.

Dimethyl 1-benzyl-3′,3′-dicyano-1′-(4-methoxyphenyl)-2′-(4-nitrostyryl)-2-oxo-2′,3′-dihydro-1′H-spiro[indoline-3,4′-pyridine]-5′,6′-dicarboxylate (3m). White solid, 74%, m.p. 236–238 °C; ¹H NMR (400 MHz, CDCl₃) δ: 8.13 (d, J = 8.7 Hz, 2H, ArH), 7.63 (d, J = 7.5 Hz, 1H, ArH), 7.44 (d, J = 7.2 Hz, 2H, ArH), 7.41–7.26 (m, 8H, ArH), 7.14 (t, J = 7.6 Hz, 1H, ArH), 6.89–6.83 (m, 4H, ArH, CH), 6.08 (dd, J = 15.7, 9.9 Hz, 1H, CH), 5.83 (d, J = 9.9 Hz, 1H, CH), 5.25 (d, J = 15.7 Hz, 1H, CH), 4.87 (d, J = 15.7 Hz, 1H, CH), 3.78 (s, 3H, OCH₃), 3.51 (s, 3H, OCH₃), 3.14 (s, 3H, OCH₃); ¹³C NMR (100 MHz, CDCl₃) δ: 174.4, 163.9, 163.0, 159.9, 151.2, 147.9, 143.2, 140.7, 138.2, 134.9, 131.2, 130.5, 128.8, 127.9, 127.7, 127.6, 126.1, 124.2, 124.0 (2C), 123.7, 111.4, 110.9, 110.1, 94.5, 60.5, 55.4, 52.6, 51.4, 45.6, 45.1; IR (KBr) ν: 3010, 2950, 2839, 1740, 1741, 1588, 1508, 1469, 1428, 1392, 1346, 1300, 1249, 1221, 1187, 1146, 1107, 1076, 1026, 970, 874, 834, 795, 754, 724 cm⁻¹; MS (m/z): HRMS (ESI) calcd for C₄₀H₃₁N₅NaO₈ ([M + Na]⁺): 732.2065, found: 732.2068.

Methyl 1-benzyl-1′-(4-chlorophenyl)-3′,3′-dicyano-2-oxo-2′-styryl-2′,3′-dihydro-1′H-spiro[indoline-3,4′-pyridine]-5′-carboxylate (4a). White solid, 78%, m.p. 206–208 °C; ¹H NMR (400 MHz, CDCl₃) δ: 7.98 (s, 1H, ArH), 7.50 (d, J = 6.8 Hz, 2H, ArH), 7.39–7.26 (m, 11H, ArH), 7.24–7.14 (m, 4H, ArH), 6.85–6.80 (m, 2H, CH, CH), 5.99 (brs, 1H, CH), 5.10 (s, 2H, CH, CH), 5.04 (d, J = 9.2 Hz, 1H, CH), 3.53 (s, 3H, OCH₃); ¹³C NMR (100 MHz, CDCl₃) δ: 172.8, 164.5, 145.3, 144.0, 141.2, 140.9, 135.1, 134.2, 133.3, 130.9, 129.7, 129.5, 128.8 (2C), 127.7 (2C), 127.2, 124.7, 123.0, 119.4, 110.9, 110.6, 110.3, 97.7, 61.9, 52.1, 51.6, 45.6, 45.0; IR (KBr) ν: 3035, 2955, 1958, 1892, 1710, 1616, 1538, 1489, 1360, 1234, 1180, 1129, 1089, 1029, 977, 925, 835, 753, 695 cm⁻¹;MS (m/z): HRMS (ESI) calcd for C₃₇H₂₇ClN₄NaO₃ ([M + Na]⁺): 633.1664, found: 633.1672.

Methyl 1-benzyl-1′-(4-bromophenyl)-3′,3′-dicyano-2-oxo-2′-styryl-2′,3′-dihydro-1′H-spiro-[indoline-3,4′-pyridine]-5′-carboxylate (4b). White solid, 82%, m.p. 200–202 °C; ¹H NMR (400 MHz, CDCl₃) δ: 7.98 (s, 1H, ArH), 7.51 (t, J = 8.8 Hz, 4H, ArH), 7.36–7.27 (m, 8H, ArH), 7.24–7.13 (m, 5H, ArH), 6.84–6.80 (m, 2H, CH, CH), 5.98 (brs, 1H, CH), 5.10 (s, 2H, CH, CH), 5.05 (d, J = 9.2 Hz, 1H, CH), 3.53 (s, 3H, OCH₃); ¹³C NMR (100 MHz, CDCl₃) δ: 172.8, 164.5, 145.2, 144.0, 141.8, 141.0, 135.1, 134.2, 132.7, 130.9, 129.5, 128.8 (2C), 127.7, 124.7, 123.0, 121.2, 119.4, 110.9, 110.5, 110.3, 97.8, 61.8, 60.4, 52.0, 51.6, 45.6, 44.9; IR (KBr) ν: 3033, 2955, 2918, 2250, 1958, 1891, 1708, 1615, 1485, 1360, 1278, 1234, 1179, 1128, 976, 924, 867, 829, 753, 697 cm⁻¹; MS (m/z): HRMS (ESI) calcd for C₃₇H₂₇BrN₄NaO₃ ([M + Na]⁺): 677.1159, found: 677.1156.

Methyl 1-benzyl-3′,3′-dicyano-1′-(4-methoxyphenyl)-5-methyl-2-oxo-2′-styryl-2′,3′-dihydro-1′H-spiro[indoline-3,4′-pyridine]-5′-carboxylate (4c). White solid, 73%, m.p. 194–196 °C; ¹H NMR (400 MHz, CDCl₃) δ: 7.94 (s, 1H, ArH), 7.41–7.39 (d, J = 7.9 Hz, 3H, ArH), 7.27 (ddd, J = 23.4, 15.1, 8.0 Hz, 10H, ArH), 7.07 (d, J = 7.8 Hz, 1H, ArH), 6.89 (dd, J = 23.9, 12.1 Hz, 3H, ArH, CH), 6.68 (d, J = 7.9 Hz, 1H, CH), 5.93 (dd, J = 15.5, 9.8 Hz, 1H, CH), 5.80 (d, J = 9.8 Hz, 1H, CH), 5.17 (d, J = 15.9 Hz, 1H, CH), 4.91 (d, J = 15.9 Hz, 1H, CH), 3.78 (s, 3H, OCH₃), 3.38 (s, 3H, OCH₃), 2.32 (s, 3H, CH₃). ¹³C NMR (100 MHz, CDCl₃) δ: 174.7, 164.8, 158.8, 147.8, 141.0, 140.5, 135.7, 135.0, 134.8, 133.2, 130.6, 129.1, 128.8, 128.7, 128.3, 127.7, 127.2 (2C), 126.2, 124.9, 120.0, 114.5, 111.9, 111.4, 109.8, 95.5, 60.1, 55.5, 52.0, 51.1, 46.2, 44.9, 21.3; IR (KBr) ν: 3085, 3061, 2997, 2947, 2834, 1702, 1593, 1503, 1439, 1351, 1305, 1228, 1175, 1100, 1029, 977, 808, 764, 710 cm⁻¹; MS (m/z): HRMS (ESI) calcd for C₃₉H₃₂N₄NaO₄ ([M + Na]⁺): 643.2316, found: 643.2333.

Methyl 1-butyl-3′,3′-dicyano-1′-(4-methoxyphenyl)-5-methyl-2-oxo-2′-styryl-2′,3′-dihydro-1′H-spiro[indoline-3,4′-pyridine]-5′-carboxylate (4d). White solid, 68%, m.p. 156–158 °C; ¹H NMR (400 MHz, CDCl₃) δ: 7.91 (s, 1H, ArH), 7.37 (s, 1H, ArH), 7.24–7.18 (m, 8H, ArH), 6.91–6.84 (m, 4H, ArH, CH, CH), 5.94–5.88 (m, 1H, CH), 5.78–5.75 (m, 1H, CH), 3.83–3.77 (m, 5H, CH₂, OCH₃), 3.41 (s, 3H, OCH₃), 2.36 (s, 3H, CH₃), 1.79–1.68 (m, 2H, CH₂), 1.48–1.42 (m, 2H, CH₂), 0.96 (t, J = 7.3 Hz, 3H, CH₃); ¹³C NMR (100 MHz, CDCl₃) δ: 174.3, 164.7, 158.8, 147.7, 140.4, 135.8, 134.8, 132.8, 130.6, 129.1, 128.6, 128.2, 127.1, 126.3, 125.0, 120.1, 114.1, 111.9, 111.1, 108.9, 95.4, 59.9, 55.5, 51.7, 51.1, 46.1, 40.9, 29.2, 21.3, 20.2, 13.7; IR (KBr) ν: 3089, 3068, 2956, 2871, 2840, 2349, 1696, 1622, 1511, 1431, 1382, 1347, 1301, 1281, 1248, 1203, 1186, 1128, 1041, 970, 933, 841, 812, 782, 760, 702 cm⁻¹; MS (m/z): HRMS (ESI) calcd for C₃₆H₃₄N₄NaO₄ ([M + Na]⁺): 609.2472, found: 609.2481.

Methyl 1-butyl-3′,3′-dicyano-1′-(4-methoxyphenyl)-5-methyl-2-oxo-2′-styryl-2′,3′-dihydro-1′H-spiro[indoline-3,4′-pyridine]-5′-carboxylate (4e). White solid, 69%, m.p. 204–206 °C; ¹H NMR (400 MHz, CDCl₃) δ: 7.97 (s, 1H, ArH), 7.42 (d, J = 8.2 Hz, 1H, ArH), 7.28–7.26 (m, 4H, ArH), 7.18–7.10 (m, 6H, ArH), 6.93 (d, J = 8.2 Hz, 1H, CH), 6.83 (d, J = 15.7 Hz, 1H, CH), 6.01 (s, 1H, CH), 4.92 (d, J = 9.2 Hz, 1H, CH), 3.90–3.85 (m, 1H, CH), 3.75–3.68 (m, 1H, CH), 3.57 (s, 3H, OCH₃), 2.34 (s, 3H, CH₃), 1.84–1.78 (m, 2H, CH₂), 1.05 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, CDCl₃) δ: 172.3, 164.6, 146.2, 143.0, 140.5, 140.0, 137.9, 134.5, 130.8, 130.7, 130.1, 129.2, 128.7, 128.6, 127.8, 127.2, 126.3, 125.3, 119.6, 110.8, 110.3, 110.1, 95.0, 61.9, 51.4, 45.4, 42.7, 21.0, 20.5, 11.5; IR (KBr) ν: 3085, 3070, 3029, 2977, 2962, 2940, 2876, 1876, 1714, 1693, 1628, 1607, 1511, 1483, 1437, 1380, 1350, 1330, 1316, 1302, 1286, 1270, 1247, 1228, 1196, 1164, 1132, 1116, 1089, 1057, 1040, 1017, 988, 969, 945, 935, 926, 910, 883, 858, 815, 787, 771, 760, 743, 722 cm⁻¹; MS (m/z): HRMS (ESI) calcd for C₃₄H₂₉ClN₄NaO₃ ([M + Na]⁺): 599.1820, found: 599.1828.

Methyl 1-benzyl-3′,3′-dicyano-5-fluoro-2-oxo-2′-styryl-1′-p-tolyl-2′,3′-dihydro-1′H-spiro-[indoline-3,4′-pyridine]-5′-carboxylate (4f). White solid, 64%, m.p. 150–152 °C; ¹H NMR (400 MHz, CDCl₃) δ: 7.99 (s, 1H, ArH), 7.47 (d, J = 7.3 Hz, 2H, ArH), 7.35–7.22 (m, 8H, ArH), 7.20–7.18 (s, 4H, ArH), 7.03–6.99 (m, 2H, ArH), 6.81 (d, J = 15.7 Hz, 1H, CH), 6.74–6.71 (m, 1H, CH), 6.02 (s, 1H, CH), 5.13–5.02 (m, 2H, CH, CH), 4.95 (d, J = 9.4 Hz, 1H, CH), 3.54 (s, 3H, OCH₃), 2.34 (s, 3H, CH₃); ¹³C NMR (100 MHz, CDCl₃) δ: 172.7, 164.6, 160.1, 157.7, 146.2, 140.3 (d, J = 16.0 Hz), 137.8, 134.8, 134.4, 130.8 (d, J = 8.4 Hz), 128.8, 128.7, 127.8, 127.5, 127.2, 126.1, 119.5, 117.2, 116.9, 113.1, 112.8, 110.8 (d, J = 8.8 Hz), 110.3, 109.9, 51.4, 45.0, 21.0; IR (KBr) ν: 3067, 3030, 2951, 1729, 1686, 1621, 1607, 1512, 1491, 1444, 1379, 1346, 1332, 1271, 1241, 1178, 1167, 1133, 1090, 1076, 1039, 1001, 970, 930, 908, 870, 820, 796, 783, 761, 736, 726 cm⁻¹; MS (m/z): HRMS (ESI) calcd for C₃₈H₂₉FN₄NaO₃ ([M + Na]⁺): 631.2116, found: 631.2123.

Methyl 1-benzyl-5-chloro-3′,3′-dicyano-1′-(4-methylphenyl)-2′-(3-methylstyryl)-2-oxo-2′,3′-dihydro-1′H-spiro[indoline-3,4′-pyridine]-5′-carboxylate (4g). White solid, 79%, m.p. 192–194 °C; ¹H NMR (400 MHz, CDCl₃) δ: 8.01 (s, 1H, ArH), 7.48 (d, J = 7.2 Hz, 2H, ArH), 7.35 (t, J = 7.2 Hz, 2H, ArH), 7.30–7.28 (m, 2H, ArH), 7.19–7.16 (m, 6H, ArH), 7.11–7.06 (m, 3H, ArH), 6.81 (d, J = 15.6 Hz, 1H, CH), 6.73 (d, J = 8.4 Hz, 1H, CH), 6.00 (brs, 1H, CH), 5.10 (s, 2H, CH, CH), 4.94 (d, J = 9.2 Hz, 1H, CH), 3.56 (s, 3H, OCH₃), 2.35 (s, 3H, CH₃), 2.29 (s, 3H, CH₃); ¹³C NMR (100 MHz, CDCl₃) δ: 172.7, 164.6, 146.4, 142.6, 140.8, 140.0, 138.4, 137.9, 134.7, 134.4, 130.7, 130.2, 128.9, 128.9, 128.6, 128.2, 127.9, 127.6, 126.3, 125.2, 124.4, 119.1, 111.2, 110.4, 95.8, 62.0, 52.2, 51.6, 45.5, 45.1, 21.3, 21.1; IR (KBr) ν: 3055, 2952, 2912, 2251, 1888, 1730, 1691, 1613, 1546, 1483, 1437, 1334, 1237, 1178, 1125, 1040, 975, 824, 776, 735, 964 cm⁻¹; MS (m/z): HRMS (ESI) calcd for C₃₉H₃₁ClN₄NaO₃ ([M + Na]⁺): 661.1977, found: 661.1984.

General procedure for the synthesis of spiro[indene-2,4′-pyridines] 5a–5f from three-component reaction

A mixture of α,β-unsaturated N-arylaldimine (1.0 mmol), dimethyl acetylenedicarboxylate (1.0 mmol) and 2-(1,3-dioxo-1H-inden-2(3H)-ylidene)malononitrile (1.0 mmol) in dry acetonitrile (15.0 mL) was stirred at room temperature for about 24 hours. After removing the solvent, the resulting oily residue was subjected to thin-layer chromatography with light petroleum and ethyl acetate (V/V = 2.5 : 1) as eluting solvent to give the pure product for analysis.

Dimethyl 3′,3′-dicyano-1,3-dioxo-1′-phenyl-2′-styryl-1,2′,3,3′-tetrahydro-1′H-spiro[indene-2,4′-pyridine]-5′,6′-dicarboxylate (5a). White solid, 72%, m.p. 160–162 °C; ¹H NMR (400 MHz, CDCl₃) δ: 8.19 (d, J = 7.1 Hz, 1H, ArH), 8.11 (d, J = 6.9 Hz, 1H, ArH), 8.03–7.95 (m, 2H, ArH), 7.46–7.29 (m, 5H, ArH), 7.28–7.25 (m, 3H, ArH), 7.18–7.12 (m, 2H, ArH, CH), 6.79 (d, J = 15.6 Hz, 1H, CH), 5.89 (dd, J = 15.4, 9.9 Hz, 1H, CH), 5.44 (d, J = 9.8 Hz, 1H, CH), 3.49 (s, 3H, OCH₃), 3.43 (s, 3H, OCH₃); ¹³C NMR (100 MHz, CDCl₃) δ: 197.8, 194.1, 164.2, 162.6, 151.7, 141.6, 141.1, 139.5, 138.5, 137.2, 136.4, 134.4, 130.3, 129.4, 129.3, 129.1, 128.7, 127.1, 124.1, 124.0, 118.4, 110.5, 109.9, 93.5, 62.3, 54.9, 52.5, 52.0, 41.2, 29.7; IR (KBr) ν: 3061, 3040, 3005, 2949, 2917, 2848, 1745, 1711, 1688, 1579, 1197, 1167, 1154, 1139, 1100, 1064, 1020, 1002, 958, 925, 882, 855, 805, 792, 778, 753, 707 cm⁻¹; MS (m/z): HRMS (ESI) calcd forC₃₃H₂₃N₃NaO₆ ([M + Na]⁺): 580.1479, found: 580.1494.

Dimethyl 3′,3′-dicyano-1,3-dioxo-2′-styryl-1′-p-tolyl-1,2′,3,3′-tetrahydro-1′H-spiro[indene-2,4′-pyridine]-5′,6′-dicarboxylate (5b). White solid, 78%, m.p. 168–170 °C; ¹H NMR (400 MHz, CDCl₃) δ: 8.15 (d, J = 7.4 Hz, 1H, ArH), 8.08 (d, J = 7.4 Hz, 1H, ArH), 8.00–7.92 (m, 2H, ArH), 7.29–7.07 (m, 9H, ArH), 6.75 (d, J = 15.6 Hz, 1H, CH), 5.88 (dd, J = 15.4, 9.9 Hz, 1H, CH), 5.38 (d, J = 9.8 Hz, 1H, CH), 3.48 (s, 3H, OCH₃), 3.40 (s, 3H, OCH₃), 2.30 (s, 3H, CH₃); ¹³C NMR (100 MHz, CDCl₃) δ: 197.9, 194.2, 164.3, 162.7, 152.0, 141.7, 140.9, 139.5, 137.2, 136.4, 135.9, 134.5, 129.9, 129.7, 129.3, 128.7, 127.1, 124.1, 124.0, 118.5, 110.5, 109.9, 93.3, 62.4, 54.9, 52.5, 52.0, 41.2, 21.2; IR (KBr) ν: 3064, 3039, 2997, 2952, 2851, 1760, 1715, 1675, 1589, 1508, 1438, 1194, 1168, 1111, 1096, 1064, 1045, 1019, 1004, 978, 945, 925, 881, 850, 817, 792, 773, 755, 714 cm⁻¹; MS (m/z): HRMS (ESI) calcd forC₃₄H₂₅N₃NaO₆ ([M + Na]⁺): 594.1636, found: 594.1638.

Dimethyl 3′,3′-dicyano-1′-(4-methoxyphenyl)-1,3-dioxo-2′-styryl-1,2′,3,3′-tetrahydro-1′H-spiro[indene-2,4′-pyridine]-5′,6′-dicarboxylate (5c). White solid, 80%, m.p. 200–202 °C; ¹H NMR (400 MHz, CDCl₃) δ: 8.18–7.93 (m, 4H, ArH), 7.38 (s, 1H, ArH), 7.26–7.18 (m, 5H, ArH), 6.88–6.72 (m, 3H, ArH, CH), 5.95–5.85 (m, 1H, CH), 5.37 (d, J = 9.5 Hz, 1H, CH), 3.78 (s, 3H, OCH₃), 3.50 (s, 3H, OCH₃), 3.41 (s, 3H, OCH₃); ¹³C NMR (100 MHz, CDCl₃) δ: 197.9, 194.2, 164.3, 162.6, 159.8, 152.2, 141.6, 140.9, 139.5, 137.2, 136.4, 134.5, 131.5, 131.1, 129.3, 128.7, 127.1, 124.1, 124.0, 118.4, 11.5, 11.0, 93.2, 62.5, 62.4, 55.4, 52.6, 51.9, 41.2, 29.7; IR (KBr) ν: 3086, 3049, 3002, 2972, 2949, 2838, 1753, 1711, 1681, 1605, 1568, 1509, 1438, 1311, 1283, 1171, 1070, 1048, 1004, 963, 943, 926, 881, 864, 852, 835, 811, 796, 770, 775, 729, 711 cm⁻¹; MS (m/z): HRMS (ESI) calcd for C₃₄H₂₅N₃NaO₇ ([M + Na]⁺): 610.1585, found: 610.1592.

Dimethyl 3′,3′-dicyano-2′-(3-methylstyryl)-1,3-dioxo-1′-phenyl-1,2′,3,3′-tetrahydro-1′H-spiro[indene-2,4′-pyridine]-5′,6′-dicarboxylate (5d). White solid, 70%, m.p. 196–198 °C; ¹H NMR (400 MHz, CDCl₃) δ: 8.16 (d, J = 7.4 Hz, 1H, ArH), 8.08 (d, J = 7.4 Hz, 1H, ArH), 8.00–7.93 (m, 2H, ArH), 7.32 (t, J = 13.5 Hz, 5H, ArH), 7.12 (t, J = 7.5 Hz, 1H, ArH), 7.05 (d, J = 7.6 Hz, 1H, ArH), 6.93 (d, J = 8.4 Hz, 2H, ArH), 6.73 (d, J = 15.6 Hz, 1H, CH), 5.84 (dd, J = 15.6, 9.8 Hz, 1H, CH), 5.39 (d, J = 9.9 Hz, 1H, CH), 3.46 (s, 3H, OCH₃), 3.40 (s, 3H, OCH₃), 2.26 (s, 3H, CH₃); ¹³C NMR (100 MHz, CDCl₃) δ: 197.9, 194.1, 164.3, 162.6, 151.8, 141.7, 141.3, 139.5, 138.6, 138.4, 137.2, 136.4, 134.3, 130.3, 130.1, 129.4, 129.1, 128.5, 127.7, 124.2, 124.1, 124.0, 118.1, 110.5, 110.0, 93.5, 62.4, 54.9, 52.5, 52.0, 41.2, 21.2; IR (KBr) ν: 3064, 3028, 3003, 2953, 2928, 1963, 1744, 1714, 1676, 1578, 1172, 1157, 1139, 1115, 1059, 1076, 1002, 981, 947, 920, 881, 858, 844, 814, 784, 767, 738 cm⁻¹; MS (m/z): HRMS (ESI) calcd for C₃₄H₂₅N₃NaO₆ ([M + Na]⁺): 594.1636, found: 594.1638.

Dimethyl 3′,3′-dicyano-1′-(4-methoxyphenyl)-2′-(3-methylstyryl)-1,3-dioxo-1,2′,3,3′-tetrahydro-1′H-spiro[indene-2,4′-pyridine]-5′,6′-dicarboxylate (5e). White solid, 75%, m.p. 188–190 °C; ¹H NMR (400 MHz, CDCl₃) δ: 8.15 (d, J = 7.1 Hz, 1H, ArH), 8.07 (d, J = 7.5 Hz, 1H, ArH), 7.99–7.91 (m, 2H, ArH), 7.38 (s, 1H, ArH), 7.15 (dd, J = 22.1, 14.6 Hz, 2H, ArH), 7.06 (d, J = 7.4 Hz, 1H, ArH), 6.96 (d, J = 7.1 Hz, 2H, ArH), 6.82 (d, J = 7.5 Hz, 2H, ArH), 6.72 (d, J = 15.6 Hz, 1H, CH), 5.87 (dd, J = 15.3, 10.0 Hz, 1H, CH), 5.35 (d, J = 9.8 Hz, 1H, CH), 3.76 (s, 3H, OCH₃), 3.49 (s, 3H, OCH₃), 3.40 (s, 3H, OCH₃), 2.27 (s, 3H, CH₃); ¹³C NMR (100 MHz, CDCl₃) δ: 197.9, 194.2, 164.3, 162.7, 159.8, 152.2, 141.7, 141.1, 139.5, 138.4, 137.2, 136.4, 134.4, 131.4, 131.1, 130.1, 128.6, 127.8, 124.3, 124.1, 124.0, 118.1, 110.5, 110.0, 93.1, 62.5, 55.4, 52.6, 51.9, 41.2, 21.2; IR (KBr) ν: 3058, 3023, 3002, 29 563, 2842, 1756, 1716, 1579, 1590, 1508, 1454, 1193, 1169, 1153, 1138, 1108, 1096, 1066, 1044, 1034, 1003, 983, 947, 880, 859, 835, 801, 788, 770, 724 cm⁻¹; MS (m/z): HRMS (ESI) calcd for C₃₅H₂₇N₃NaO₇ ([M + Na]⁺): 624.1741, found: 624.1744.

Dimethyl 1′-(4-bromophenyl)-3′,3′-dicyano-2′-(3-methylstyryl)-1,3-dioxo-1,2′,3,3′-tetrahydro-1′H-spiro[indene-2,4′-pyridine]-5′,6′-dicarboxylate (5f). White solid, 68%, m.p.208–210 °C; ¹H NMR (400 MHz, CDCl₃) δ: 8.15 (d, J = 7.3 Hz, 1H, ArH), 8.08 (d, J = 7.3 Hz, 1H, ArH), 8.00–7.93 (m, 2H, ArH), 7.48 (d, J = 8.4 Hz, 2H, ArH), 7.25 (s, 2H, ArH), 7.16 (s, 1H, ArH), 7.09 (d, J = 7.6 Hz, 1H, ArH), 6.97 (s, 2H, ArH), 6.75 (d, J = 15.6 Hz, 1H, CH), 5.82 (dd, J = 15.6, 9.9 Hz, 1H, CH), 5.36 (d, J = 9.9 Hz, 1H, CH), 3.51 (s, 3H, OCH₃), 3.40 (s, 3H, OCH₃), 2.28 (s, 3H, CH₃); ¹³C NMR (100 MHz, CDCl₃) δ: 197.6, 193.9, 164.1, 162.5, 151.3, 141.8, 141.6, 139.5, 138.5, 137.6, 137.3, 136.5, 134.1, 132.3, 131.9, 130.4, 128.7, 127.8, 124.3, 124.2, 124.1, 123.6, 117.6, 110.3, 109.9, 94.5, 62.4, 54.9, 52.7, 52.1, 41.3, 21.2; IR (KBr) ν: 3089, 3057, 2957, 2920, 2844, 1749, 1708, 1593, 1575, 1488, 1434, 1401, 1384, 1191, 1167, 1155, 1104, 1072, 1012, 973, 879, 863, 835, 814, 770, 745, 724, 706 cm⁻¹; MS (m/z): HRMS (ESI) calcd for C₃₄H₂₄BrN₃NaO₆ ([M + Na]⁺): 672.0741, found: 672.0738.

Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (Grant No. 21172189) and the Priority Academic Program Development of Jiangsu Higher Education Institutions.

References

1. A. A. Patchett, R. P. Nargund, J. R. Tata, M.-H. Chen, K. J. Barakat, D. B. R. Johnston, K. Cheng, W. W.-S. Chan, B. Butler, G. Hickey, T. Jacks, K. Schleim, S.-S. Pong, L.-Y. P. Chaung, H. Y. Chen, E. Frazier, K. H. Leung, S.-H. L. Chiu and R. G. Smith, Proc. Natl. Acad. Sci. U. S. A., 1995, 92, 7001.
2. (a) D. Rampe and J. M. Kane, Drug Dev. Res., 1994, 33, 344; (b) M. F. Gordeev, D. V. Patel and E. M. Gordon, J. Org. Chem., 1996, 61, 924; (c) N. Buckley, A. Dawson and I. Whyte, Medicine, 2007, 35, 599; (d) C. O. Kappe, Eur. J. Med. Chem., 2000, 35, 1043.
3. (a) A. Saini, S. Kumar and J. S. Sandhu, J. Sci. Ind. Res., 2008, 67, 95; (b) D. Schade, M. Lanier, E. Willems, K. Okolotowicz, P. Bushway, C. Wahlquist, C. Gilley, M. Mercola and J. R. Cashman, J. Med. Chem., 2012, 55, 9946.
4. (a) J. L. Harper, C. S. Camerini-Otero, A. H. Li, S. A. Kim, K. A. Jacobson and J. W. Daly, Biochem. Pharmacol., 2003, 65, 329–338; (b) A. Zarghi, H. Sadeghi, A. Fassihi, M. Faizi and A. Shafiee, Farmaco, 2003, 58, 1077–1081.
5. (a) F. Bossert, H. Meyer and E. Wehinger, Angew. Chem., Int. Ed. Engl., 1981, 20, 762–769; (b) S. Goldman and J. Stoltefuss, Angew. Chem., Int. Ed. Engl., 1991, 30, 1559–1578; (c) F. Bossert and W. Vater, Med. Res. Rev., 1989, 9, 291–324.
6. (a) D. M. Stout and A. I. Meyers, Chem. Rev., 1982, 82, 223; (b) R. Lavilla, J. Chem. Soc., Perkin Trans. 1, 2002, 1141; (c) J. A. Bull, J. J. Mousseau, G. Pelletier and A. B. Charette, Chem. Rev., 2012, 112, 2642; (d) J. P. Wan and Y. Liu, RSC Adv., 2012, 2, 9763.
7. (a) L. Sambri, Synlett, 2007, 2897; (b) R. K. Vohra, C. Bruneau and J.-L. Renaud, Adv. Synth. Catal., 2006, 348, 2571; (c) V. Sridharan, P. T. Perumal, C. Avendano and J. C. Menendez, Tetrahedron, 2007, 63, 4407; (d) A. Noole, M. Borissova, M. Lopp and T. Kanger, J. Org. Chem., 2011, 76, 1538.
8. (a) X. Ji, H. Huang, W. Wu, X. Li and H. Jiang, J. Org. Chem., 2013, 78, 11155; (b) C. Baumert, M. Gunthel, S. Krawczyk, M. Hemmer, T. Wersig, A. Langner, J. Molnar, H. Lage and A. Hilgeroth, Bioorg. Med. Chem., 2013, 21, 166; (c) A. T. Khan and M. M. Khan, Tetrahedron Lett., 2011, 52, 3455; (d) J. P. Wan, S.-F. Gan, G. L. Sun and Y. J. Pan, J. Org. Chem., 2009, 74, 2862.
9. (a) L. Singh, M. P. S. Ishar, M. Elango, V. Subramanian, V. Gupta and P. Kanwal, J. Org. Chem., 2008, 73, 2224; (b) M. P. S. Ishar, K. Kumar, S. Kaur, S. Kumar, N. K. Girdhar, S. Sachar, A. Marwaha and A. Kapoor, Org. Lett., 2001, 3, 2133; (c) G. Sabitha, G. S. K. K. Reddy, C. S. Reddy and J. S. Yadav, Tetrahedron Lett., 2003, 44, 4129–4131.
10. (a) J. Sun, E. Y. Xia, Q. Wu and C. G. Yan, Org. Lett., 2010, 12, 3678–3681; (b) J. Sun, Q. Wu, E. Y. Xia and C. G. Yan, Eur. J. Org. Chem., 2011, 2981–2986; (c) J. Sun, Y. Sun, E. Y. Xia and C. G. Yan, ACS Comb. Sci., 2011, 13, 436–441; (d) J. Sun, Y. Sun, H. Gao and C. G. Yan, Synthesis, 2012, 1069–1073; (e) Y. Sun, J. Sun and C. G. Yan, Mol. Diversity, 2012, 16, 163–171; (f) L. L. Zhang, J. Sun and C. G. Yan, Tetrahedron Lett., 2012, 53, 6965–6967.
11. (a) B. L. Palucki, S. D. Feighner, S. S. Pong, K. K. McKee, D. L. Hreniuk, C. Tan, A. D. Howard, L. H. Y. van der Ploeg, A. A. Patchetta and R. P. Nargunda, Bioorg. Med. Chem. Lett., 2001, 11, 1955–1957; (b) L. B. Ye, Y. X. Tian, Z. H. Li, H. Jin, Z. G. Zhu, S. H. Wan, J. Y. Zhang, P. J. Yu, J. J. Zhang and S. G. Wu, Eur. J. Med. Chem., 2012, 50, 370–375.
12. (a) A. A. Esmaili and A. Bodaghi, Tetrahedron, 2003, 59, 1169–1171; (b) A. A. Esmaeili and M. Darbanian, Tetrahedron, 2003, 59, 5545–5548; (c) I. Yavari, S. Seyfi and Z. Hossaini, Tetrahedron Lett., 2010, 51, 2193–21949; (d) Z. N. Tisseh, F. Ahmadi, M. Dabiri, H. R. Khavasi and A. Bazgir, Tetrahedron Lett., 2012, 53, 3603–3606; (e) V. Nair, A. U. Vinod, N. Abhilash, R. S. Menon, V. Santhi, R. L. Varma, S. Viji, S. Mathewa and R. Srinivas, Tetrahedron, 2003, 59, 10279–10286; (f) A. A. Esmaelli and M. Nazer, Synlett, 2009, 2119–2122; (g) A. A. Esmaeili, H. Vesalipoor, R. Hosseinabadi, A. F. Zavareh, N. A. Naseri and E. Ghiamati, Tetrahedron Lett., 2011, 52, 4865–4867.
13. (a) A. Alizadeh and J. Mokhtari, Tetrahedron, 2011, 67, 3519–3523; (b) Y. A. Ammar, M. M. Ali, Y. A. Mohamed, H. K. Thabet and M. S. A. El-Gaby, Heterocycl. Commun., 2013, 19, 195–200; (c) Y. R. Liang, X. Y. Chen, Q. Wu and X. F. Lin, Tetrahedron, 2015, 71, 616–621; (d) A. Dandia, A. K. Laxkar and R. Singh, Tetrahedron Lett., 2012, 53, 3012–3017; (e) N. Y. Chen, L. P. Ren, M. M. Zou, z. P. Xu, X. S. Shao, X. Y. Xu and Z. Li, Chin. Chem. Lett., 2014, 25, 197–200; (f) R. Ghahremanzadeh, Z. Rashid, A. H. Zarnani and H. Naeimi, Ultrason. Sonochem., 2014, 21, 1451–1460.
14. (a) J. Sun, Q. Wu, L. J. Zhang and C. G. Yan, Chin. J. Chem., 2012, 30, 1548–1554; (b) L. J. Zhang, Q. Wu, J. Sun and C. G. Yan, Beilstein J. Org. Chem., 2013, 9, 846–851; (c) H. Gao, J. Sun and C. G. Yan, Mol. Diversity, 2014, 18, 511–519; (d) C. Wang, Y. H. Jiang and C. G. Yan, Beilstein J. Org. Chem., 2014, 10, 2671–2676; (e) H. Gao, J. Sun and C. G. Yan, J. Org. Chem., 2014, 79, 4131–4136; (f) H. Gao, J. Sun and C. G. Yan, Mol. Diversity, 2014, 18, 511–519.
15. (a) A. Dömling and I. Ugi, Angew. Chem., Int. Ed., 2000, 39, 3168–3210; (b) A. Dömling, Chem. Rev., 2006, 106, 17–89; (c) E. Ruijter, R. Scheffelaar and R. V. A. Orru, Angew. Chem., Int. Ed., 2011, 50, 6234–6246.
16. (a) N. Isambert and R. Lavilla, Chem.–Eur. J., 2008, 14, 8444–8454; (b) B. A. Arndtsen, Chem.–Eur. J., 2009, 15, 302–313; (c) S. F. Martin, Chem.–Eur. J., 2009, 15, 1300–1308.
17. V. Nair, S. Devipriya and E. Suresh, Tetrahedron, 2008, 64, 3567–3577.
18. H. B. Yang, X. Y. Guan, Y. Wei and M. Shi, Eur. J. Org. Chem., 2012, 2792–2800.
19. S. E. Kiruthika, N. V. Lakshmi, B. R. Banu and P. T. Perumal, Tetrahedron Lett., 2011, 52, 6508–6511.
20. (a) J. Sun, Q. Wu, L. J. Zhang and C. G. Yan, Chin. J. Chem., 2012, 30, 1548–1554; (b) L. J. Zhang, Q. Wu, J. Sun and C. G. Yan, Beilstein J. Org. Chem., 2013, 9, 846–851.
21. (a) M. Lei, Z. J. Zhan, W. Tian and P. Lu, Tetrahedron, 2012, 68, 3361–3367; (b) M. Lei, W. Tian, W. Li, P. Lu and Y. G. Wang, Tetrahedron, 2014, 70, 3665–3674; (c) Y. F. Li, J. Shi, Z. G. Wu, X. L. Wang, X. W. Wu, J. C. Gu, H. Z. Bu and H. F. Ma, Tetrahedron, 2014, 70, 2472–2477; (d) Y. F. Li, Z. G. Wu, J. Shi, Y. Pan, H. Z. Bu, H. F. Ma, J. C. Gu, H. Huang, Y. Z. Wang and L. Wu, Tetrahedron, 2014, 70, 8971–8975.
22. (a) J. Zhang and C. G. Yan, Eur. J. Org. Chem., 2014, 5598–5602; (b) J. Zhang and C. G. Yan, Tetrahedron, 2015, 71, 6681–6688.

---

Footnote

† Electronic supplementary information (ESI) available: Experimental procedures and spectral data for all new compounds. CCDC 1408944–1408946 and 1415163. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5ra15139b

---