Literature DB >> 23868182

Synthesis of spiro[indoline-3,1'-quinolizines] and spiro[indoline-3, 4'-pyrido[1,2-a]quinolines] via three-component reactions of azaarenes, acetylenedicarboxylate, and 3-methyleneoxindoles.

Jing Sun1, Hui Gong, Yan Sun, Chao-Guo Yan.   

Abstract

The three-component reactions of substituted pyridines, dimethyl acetylenedicarboxylates, and 3-phenacylideneoxindoles afforded spiro[indoline-3,1'quinolizines] in high yields and with high diastereoselectivity. The Diels-Alder reactions of spiro[indoline-3,1' quinolizines] with maleic anhydride and N- phenyl maleimides successfully resulted in polyfunctionalized isoquinolinuclidine derivatives. The similar three-component reactions with quinoline resulted in the novel spiro[indoline-3,4' -pyrido[1,2-a]quinolines] in moderate to good yields.

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Year:  2013        PMID： 23868182      PMCID： PMC3836201          DOI： 10.1007/s11030-013-9459-5

Source DB:  PubMed          Journal:  Mol Divers        ISSN： 1381-1991            Impact factor:   2.943


Introduction

The spirooxindole core is a privileged heterocyclic ring system that is featured in a large number of bioactive naturally occurring alkaloids and medicinally relevant compounds [1-5]. Due to the exceptional high reactivity of the 3-carbonyl group, 3-methylene and 3-phenacylideneoxindoles have attracted a lot of attention for synthetic reactions, especially multicomponent reactions [6-8] and catalytic asymmetric reactions [9-11] in the past few years. As a result, numerous elegant transformations have been developed for the diastereoselective and enantioselective construction of versatile spirooxindole skeletons [12-17]. For the synthesis of these challenging heterocycles, the 1,4-dipolar cycloaddition of Huisgen 1,4-dipoles, which were generated from reactions of nitrogen heterocycles with electron-deficient alkynes, has proven to be a convenient and efficient synthetic methodology [18, 19]. Nair et al. [20] first reported the three-component reaction of pyridine, dimethyl acetylenedicarboxylate (DMAD), and -benzylisatins to give spiro[indololine-3,2-pyrido[2,1-b][1,3]oxazine]. Later, Yavari [21] and Nair [22] reported the similar reactions of quinoline and isoquinoline with DMAD and isatins for the preparation of complex spirooxindole derivatives. Shi and co-workers [23] found that the three-component reactions of pyridine, DMAD, and -substituted isatylidene derivatives afforded spiro[indoline-3,2-quinolizine] in high yields and with good diastereoselectivities. Recently, we successfully developed an efficient synthetic protocol for dispirooxindole-fused heterocycles via the domino reaction of -dimethylaminopyridine and DMAD with two molecules of 3-phenacylideneoxindoles [24]. In order to demonstrate the synthetic utility of this practical method, herein we wish to report the three-component reaction of azaarenes such as substituted pyridines and quinoline with DMAD and 3-phenacylideneoxindoles and 3-ethoxycarbonylmethyleneoxindoles for the synthesis of spiro [indoline-3,1-quinolizine] derivatives and their potential applications as effective dienes for Diels–Alder reactions.

Results and discussion

We initiated our studies by evaluating the reactivity of the Huisgen 1,4-dipoles generated from the reaction of alkylpyridines with DMAD. According to our previously established conditions for the reaction of 4-dimethylaminopyridine [24], the three-component reactions of 2-picoline with DMAD and 3-phenacylideneoxindoles in THF at room temperature proceeded very smoothly to give the expected 2,9a-dihydrospiro[indoline-3,1-quinolizine] 1a–1b in moderate yields (Table 1, entries 1–2). Under similar conditions, the reactions with 3-picoline and 4-picoline gave the corresponding spiro products 1c–1h in high yields (Table 1, entries 3–8). When 4-methoxypyridine was utilized in the reactions, much higher yields of spiro compounds 1j–1o (Table 1, entries 9–15) were obtained.
Table 1

Synthesis of 2,9a-dihydrospiro[indoline-3,1-quinolizine]s 1a–1o

1a–1o
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Reaction conditions Substituted pyridine (1.2 mmol), DMAD (1.2 mmol) and 3-phenacylideneoxindole (1.0 mmol) in THF (10.0 mL), rt, 6 h

Isolated yield

Synthesis of 2,9a-dihydrospiro[indoline-3,1-quinolizine]s 1a–1o Reaction conditions Substituted pyridine (1.2 mmol), DMAD (1.2 mmol) and 3-phenacylideneoxindole (1.0 mmol) in THF (10.0 mL), rt, 6 h Isolated yield The structures of the prepared 2,9a-dihydrospiro[indoline-3,1-quinolizin]-2-ones 1a–1n were fully characterized by H NMR, C NMR, HRMS, and IR. The H NMR spectra of the spiro compounds 1a–1n usually show one set of signals for the characteristic groups in the molecule, which clearly indicated that only one diastereoisomer existed in each sample. The molecular structures of compounds 1f (Fig. 1), 1h (SPI, Fig. s1), and 1m (SPI, Fig. s2) were successfully confirmed by single-crystal X-ray diffraction. These three molecules (1f, 1h, 1m) have the same stereochemistry. In the newly formed tetrahydropyridyl ring, the two protons at 2- and 4-positions are in cis-orientation. The benzoyl and aryl groups of the oxindole moiety also exist in cis-position. It is reported that the benzoyl group and aryl group of oxindole moiety exist in cis-position in the starting 3-phenacylideneoxindoles [25, 26] indicating that this configuration is expected to be retained in the reaction. Thus, we unambiguously ascertained that compounds 1a–1o are the cis-isomers proving that this three-component reaction undergoes with very high diastereoselectivity.
Fig. 1

ORTEP representation of crystal structure of spiro compound 1f

ORTEP representation of crystal structure of spiro compound 1f It should be pointed out that spiro compounds 1i–1o derived from the reactions with 4-methoxypyridine are not very stable in solution because of the presence of a reactive methyl vinyl ether moiety. The 4-methoxy group could be slowly transformed into the 4-carbonyl group during the purification process when dissolved in THF, DCM, ethyl acetate, and toluene (Scheme 1). The structures of the two spiro compounds 2a–2b were successfully characterized via spectroscopic methods, and the structure of spiro compound 2b was also confirmed by X-ray diffraction (SPI, Fig. s3). Formation of 2,8-dioxo-2,8,9,9a-tetrahydrospiro[indoline-3,1-quinolizines] To further demonstrate the substrate scope and the diastereoselectivity of this three-component reaction, quinoline was also utilized in the reaction. The three-component reaction of quinoline, DMAD, and 3-phenacylideneoxindoles in THF usually resulted in a complex mixture. After exploring different solvents, we were pleased to find that the reaction proceeded smoothly in DME to give the desired 3,4a-dihydrospiro[indoline-3,4-pyrido[1,2-a]quinolines] 3a–3e in moderate yields after thin-layer chromatography (Table 2, entries 1–5). Under similar conditions, the reactions with 3-ethoxycarbonylmethyleneoxindoles afforded the spiro [indoline-3,4-pyrido[1,2-a]quinolines] 3f–3j with much better yields (Table 2, entries 6–10). The structures of spiro compounds 3a–3j were also confirmed using spectroscopic methods and compounds 3e and 3i were further confirmed by X-ray diffraction (Figs. 2, 3, respectively). A stereochemistry similar to that of 1a–1o was observed for the spiro compounds 3a–3j, in which the two protons at 2- and 4-positions existed in cis-orientation in the newly formed tetrahydropyridyl ring, and the benzoyl group and the aryl group of the oxindole moiety also existed in cis-position. These results also indicate that this three-component reaction is a high diastereoselective reaction.
Table 2

Synthesis of 3,4a-dihydrospiro[indoline-3,4-pyrido[1,2-a]quinolines] 3a–3j

3a–3j
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7 3g HBnOEt63
8 3h ClBnOEt70
9 3i Cl n-BuOEt73
10 3j FBnOEt65

Reaction conditions Quinoline (1.5 mmol), DMAD (1.5 mmol), and 3-methyleneoxindole (1.0 mmol) in DME (10.0 mL), rt, 6 h Isolated yield

Fig. 2

X-ray structure of spiro compound 3e

Fig. 3

X-ray structure of spiro compound 3i

X-ray structure of spiro compound 3e X-ray structure of spiro compound 3i Synthesis of 3,4a-dihydrospiro[indoline-3,4-pyrido[1,2-a]quinolines] 3a–3j Reaction conditions Quinoline (1.5 mmol), DMAD (1.5 mmol), and 3-methyleneoxindole (1.0 mmol) in DME (10.0 mL), rt, 6 h Isolated yield There is a 1,2-dihydropyridyl moiety in the above-prepared dihydrospiro[indoline-3,1-quinolizin]-2-ones 1a–1n. 1,2-Dihydropyridine is an effective diene for Diels–Alder reaction to construct versatile bridged heterocyclic compounds [27-33]. Thus, we proceeded to investigate the role of our spiro compounds 1a–1n as dienophiles in Diels–Alder reactions. The reaction of dihydrospiro[indoline-3,1-quinolizines] with a slight excess of -phenyl maleimides or maleic anhydride proceeded smoothly in refluxing 1,2-dimethoxyethane for 6 h to give the desired 1,4-cycloaddition products 4a–4g in satisfactory yields (Table 3). H NMR data and single-crystal determination of compound 4d (Fig. 4) indicated that the configuration of previous dihydrospiro[indoline-3,1-quinolizine] moiety is retained and the maleimide unit exists in exo-configuration in this Diels–Alder reaction.
Table 3

Diels–Alder reactions of 2,9a-dihydrospiro[indoline-3,1-quinolizines]

4a–4g
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7 4g 4-OCH\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$_{3}$$\end{document}3 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p$$\end{document}p-CH\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$_{3}$$\end{document}3C\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$_{6}$$\end{document}6H\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$_{4}$$\end{document}4 F n-C\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$_{4}$$\end{document}4H\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$_{9}$$\end{document}9 O88

Reaction conditions Spiro[indoline-3,1-quinolizine] (1.0 mmol) and -substituted maleimide or maleic anhydride (1.5 mmol) in DME (10.0 mL), reflux, 12 h

Isolated yield

Fig. 4

ORTEP representation of crystal structure of spiro compound 4d

ORTEP representation of crystal structure of spiro compound 4d Diels–Alder reactions of 2,9a-dihydrospiro[indoline-3,1-quinolizines] Reaction conditions Spiro[indoline-3,1-quinolizine] (1.0 mmol) and -substituted maleimide or maleic anhydride (1.5 mmol) in DME (10.0 mL), reflux, 12 h Isolated yield

Conclusion

In summary, an efficient protocol for the synthesis of functionalized spiro[indoline-3,1-quinolizine] and spiro[indoline-3,4-pyrido[1,2-a]quinoline] was successfully developed by three-component reactions of nitrogen heterocycles, DMADs, and 3-methyleneoxindoles. This MCR reaction can proceed smoothly under mild conditions to afford complex heterocycles in moderate to good yields and high diastereoselectivities. Furthermore, the prepared spiro[indoline-3,1-quinolizines] can undergo Diels–Alder reactions with maleic anhydride and -phenyl maleimides to give complex isoquinolinuclidine derivatives. The simplicity of the procedure, readily available substrates, and ease of handling render this protocol applicable for the synthesis of structurally diverse heterocyclic compounds.

Experimental section

General procedure for the three-component reaction of substituted pyridine, DMAD, and 3-phenacylideneoxindoles

A mixture of substituted pyridine (1.2 mmol), DMAD (1.2 mmol, 0.170 g), and 3-phenacylideneoxindole (1.0 mmol) in 10.0 mL of tetrahydrofuran was stirred at room temperature for 6 h. Then, the solvent was removed by evaporation and the residue was subjected to thin-layer chromatography (15 25 cm SiO plate) with a mixture of light petroleum and ethyl acetate (V/V = 2:1) as the developing reagent. The product was separated from silica gel by eluting with ethanol and is pure enough for spectroscopic analysis.

Dimethyl 1-benzyl-6-methyl-2-(4-methylbenzoyl)-2-oxo-2,9a-dihydrospiro[indoline-3,1-quinolizine]-3 ,4-dicarboxylate ()

Yellow solid, 66 %, m.p. 173–175 C; H NMR (600 MHz, DMSO-: 7.26 (br s, 2H, ArH), 7.20 (br s, 2H, ArH), 7.15–7.13 (m, 4H, ArH), 7.06 (br s, 2H, ArH), 6.89 (br s, 3H, ArH), 6.58 (br s, 1H, CH), 5.60 (brs, 1H, CH), 5.27 (s, 1H, CH), 4.98 (br s, 1H, CH), 4.61 (br s, 2H, CH), 4.50 (br s, 1H, CH), 3.87 (s, 3H, OCH, 3.56 (s, 3H, OCH, 2.32 (s, 3H, CH, 1.93 (s, 3H, CHC NMR (150 MHz, CDCl: 196.5, 174.2, 166.3, 166.1, 146.7, 143.4, 136.8, 135.1, 134.9, 128.9, 128.6, 128.4, 128.2, 127.4, 127.1, 126.9, 125.4, 124.9, 122.1, 116.1, 113.9, 108.5, 103.1, 66.8, 58.4, 53.3, 52.2, 49.2, 43.9, 21.7, 20.6; IR (KBr) : 3447, 2946, 2025, 1732, 1710, 1685, 1655, 1611, 1578, 1489, 1465, 1437, 1405, 1368, 1291, 1232, 1177, 1129, 1080, 1017, 963, 815, 793, 738 cm; MS (/: HRMS (ESI) Calcd. for CHNO ([M+H]: 589.2347. Found: 589.2350.

Diethyl 1-butyl-5,6-dimethyl-2-(4-methylbenzoyl)-2-oxo- 2,9a-dihydrospiro[indoline-3,1-quinolizine]-3,4- dicarboxylate ()

Yellow solid, 53 %, m.p. 161–163 C; H NMR (600 MHz, DMSO-: 7.39 (d, = 7.8 Hz, 2H, ArH), 7.18 (d, = 7.2 Hz, 2H, ArH), 7.03–7.01 (m, 2H, ArH), 6.73 (d, = 7.8 Hz, 1H, ArH), 6.21 (d, = 7.8 Hz, 1H, CH), 5.50–5.47 (m, 1H, CH), 5.23 (s, 1H, CH), 4.93–4.91 (m, 1H, CH), 4.65 (d, = 9.6 Hz, 1H, CH), 3.95 (s, 3H, OCH, 3.39 (s, 3H, OCH, 3.24–3.21 (m, 1H, CH), 3.08–3.04 (m, 1H, CH), 2.32 (s, 3H, CH, 2.24 (s, 3H, CH, 1.67 (s, 3H, CH, 0.95 (br s, 3H, CH), 0.69 (t, = 7.2 Hz, 3H, CHC NMR (150 MHz, DMSO-: 196.9, 172.8, 165.1, 164.3, 144.4, 143.2, 139.4, 130.6, 128.9, 128.6, 128.0, 127.8, 127.7, 126.7, 121.1, 121.0, 107.9, 101.9, 63.7, 53.3, 53.0, 51.3, 44.5, 28.4, 21.1, 21.0, 19.4, 13.5; IR (KBr) : 3452, 2952, 2869, 2025, 1747, 1698, 1659, 1615, 1582, 1496, 1436, 1362, 1269, 1237, 1151, 1115, 1083, 1048, 936, 866, 827, 779, 740, 701 cm; MS (/: HRMS (ESI) Calcd. for CHNO ([M+H]: 569.2686. Found: 569.2671.

Dimethyl 1-benzyl-2-(4-methoxybenzoyl)-7-methyl-2-oxo- 2,9a-dihydrospiro[indoline-3,1-quinolizine]-3,4- dicarboxylate ()

Yellow solid, 61 %, m.p. 190–192 C; H NMR (600 MHz, DMSO-: 7.51 (d, = 7.8 Hz, 2H, ArH), 7.18 (t, = 7.2 Hz, 1H, ArH), 7.11 (t, = 7.8 Hz, 4H, ArH), 6.98–6.93 (m, 3H, ArH), 6.81 (d, = 7.2 Hz, 2H, ArH), 6.69 (d, = 7.8 Hz, 1H, ArH), 6.05 (s, 1H, CH), 5.54 (d, = 8.4 Hz, 1H, CH), 5.35 (s, 1H, CH), 4.91–4.90 (m, 2H, CH), 4.64 (d, = 15.7 Hz, 1H, CH), 4.49 (d, = 15.7 Hz, 1H, CH), 3.95 (s, 3H, OCH, 3.82 (s, 3H, OCH, 3.43 (s, 3H, OCH, 1.43 (s, 3H, CHC NMR (150 MHz, CDCl: 195.8, 174.8, 166.1, 165.3, 163.3, 145.6, 142.6, 135.2, 130.5, 130.4, 128.6, 128.5, 128.2, 127.6, 127.5, 126.9, 125.9, 123.0, 122.5, 116.0, 113.4, 109.5, 108.6, 104.6, 62.7, 55.4, 54.1, 53.4, 51.6, 47.4, 43.9, 17.5; IR (KBr) : 3450, 2949, 2843, 2026, 1742, 1708, 1674, 1609, 1582, 1510, 1489, 1464, 1434, 1412, 1380, 1308, 1244, 1172, 1125, 1021, 983, 941, 899, 825, 776, 746 cm; MS (/: HRMS (ESI) Calcd. for CHNO ([M+H]: 605.2282. Found: 605.2290.

Dimethyl 1-benzyl-5-fluoro-2-(3-methoxybenzoyl)-7-methyl-2-oxo-2,9a-dihydrospiro[indo line-3,1-quinolizine]-3,4-dicarboxylate ()

Yellow solid, 58 %, m.p. 172–173 C; H NMR (600 MHz, DMSO-: 7.36 (brs, 1H, ArH), 7.18–7.13 (m, 5H, ArH), 7.05–7.00 (m, 2H, ArH), 6.85 (br s, 3H, ArH), 6.74 (br s, 1H, ArH), 6.11 (s, 1H, CH), 5.59 (br s, 1H,CH), 5.41 (s, 1H, CH), 4.97–4.93 (m, 2H, CH), 4.60 (br s, 1H,CH), 4.48 (br s, 1H,CH), 3.97 (s, 3H, OCH, 3.73 (s, 3H, OCH, 3.45 (s, 3H, OCH, 1.47 (s, 3H, CHC NMR (150 MHz, CDCl: 197.1, 174.4, 165.5 (d, = 134.6 Hz), 159.5, 145.7, 138.8, 138.7, 134.9, 129.3, 128.8, 128.5, 127.7, 126.9, 122.5, 120.8, 120.3, 115.7, 115.5 (d, = 24.9 Hz), 115.1 (d, = 24.3 Hz), 111.5, 109.7, 109.1 (d, = 5.7 Hz), 104.3, 62.6, 55.4, 54.4, 53.4, 51.7, 47.9, 44.1, 17.5; IR (KBr) : 3451, 2948, 2839, 2025, 1742, 1710, 1612, 1582, 1486, 1452, 1433, 1410, 1342, 1294, 1251, 1194, 1176, 1117, 1050, 1009, 983, 946, 896, 868, 841, 813, 788, 752 cm; MS (/: HRMS (ESI) Calcd. for CHFNO ([M+H]: 623.2201. Found: 623.2196.

Dimethyl 1-benzyl-5-chloro-7-methyl-2-(4- methylbenzoyl)-2-oxo-2,9a-dihydrospiro[indo-line-3,1- quinolizine]-3,4-dicarboxylate ()

Yellow solid, 62 %, m.p. 169–172 C; H NMR (600 MHz, DMSO-: 7.48 (d, = 7.8 Hz, 2H, ArH), 7.24 (d, = 7.8 Hz, 3H, ArH), 7.19 (t, = 7.2 Hz, 1H, ArH), 7.12–7.09 (m, 3H, ArH), 6.76 (d, = 7.2 Hz, 2H, ArH), 6.72 (d, = 8.4 Hz, 1H, ArH), 6.11 (s, 1H, CH), 5.59 (d, = 9.6 Hz, 1H, CH), 5.42 (s, 1H, CH), 4.96 (s, 1H, CH), 4.91 (d, = 9.6 Hz, 1H, CH), 4.64 (d, = 15.6 Hz, 1H, CH), 4.45 (d, = 15.6 Hz, 1H, CH), 3.97 (s, 3H, OCH, 3.43 (s, 3H, OCH, 2.36 (s, 3H, CH, 1.47 (s, 3H, CHC NMR (150 MHz, CDCl: 196.7, 174.2, 165.9, 165.1, 145.6, 143.7, 141.2, 134.8, 134.7, 129.0, 128.7, 128.6, 128.4, 127.8, 127.6, 126.9, 122.6, 115.5, 109.8, 109.6, 104.6, 62.6, 54.3, 53.5, 51.7, 47.7, 43.9, 21.7, 17.5; IR (KBr) : 3446, 3040, 2948, 2853, 2025, 1716, 1680, 1611, 1584, 1482, 1434, 1404, 1371, 1295, 1243, 1178, 1115, 1076, 983, 942, 899, 801, 743, 703 cm; MS (/: HRMS (ESI) Calcd. for CHClNO ([M+H]: 623.1957. Found: 623.1958.

Dimethyl 1-butyl-5-fluoro-2-(4-methoxybenzoyl)-7- methyl-2-oxo-2,9a-dihydrospiro[indo-line-3,1- quinolizine]-3,4-dicarboxylate ()

Yellow solid, 74 %, m.p. 162–163 C; H NMR (600 MHz, DMSO-: 7.44 (d, = 9.0 Hz, 2H, ArH), 7.09 (td, = 9.0 Hz, = 2.4 Hz, 1H, ArH), 6.90–6.89 (m, 3H, ArH), 6.82 (dd, = 8.7 Hz, = 2.4 Hz, 1H, ArH), 6.09 (s, 1H, CH), 5.62 (d, = 9.6 Hz, 1H, CH), 5.28 (s, 1H, CH), 4.92–4.90 (m, 1H, CH), 4.88 (brs, 1H, CH), 3.96 (s, 3H, OCH, 3.79 (s, 3H, OCH, 3.42 (s, 3H, OCH, 3.40–3.36 (m, 1H, CH), 3.25–3.21 (m, 1H, CH), 1.48 (s, 3H, CH, 0.99–0.91 (m, 3H, CH), 0.79–0.73 (m, 1H, CH), 0.69 (t, = 7.2 Hz, 3H, CHC NMR (150 MHz, DMSO-: 195.8, 174.0, 165.9, 165.1, 163.3, 158.9 (d, = 119.5 Hz), 145.5, 138.9, 130.5, 130.4, 128.2, 127.9, 127.8, 122.5, 115.8, 115.6 (d, = 25.2 Hz), 114.9 (d, = 23.9 Hz), 113.3, 109.6, 108.1 (d, = 8.3 Hz), 104.3, 62.2, 55.3, 54.1, 53.3, 51.6, 47.4, 40.0, 29.1, 20.0, 17.5, 13.6; IR (KBr) : 3453, 2955, 2924, 2867, 2025, 1746, 1708, 1680, 1600, 1582, 1490, 1455, 1403, 1368, 1329, 1305, 1262, 1237, 1172, 1107, 1076, 1027, 1000, 981, 952, 895, 849, 815, 758 cm; MS (/: HRMS (ESI) Calcd. for CHFNO ([M+H]: 589.2358. Found: 589.2353.

Dimethyl 1-butyl-5-fluoro-2-(4-methoxybenzoyl)-8- methyl-2-oxo-2,9a-dihydrospiro[indo-line-3,1- quinolizine]-3,4-dicarboxylate ()

Yellow solid, 77 %, m.p. 164–166 C; H NMR (600 MHz, DMSO-: 7.42 (d, = 7.2 Hz, 2H, ArH), 7.08 (br s, 1H, ArH), 6.89 (d, = 7.2 Hz, 3H, ArH), 6.79 (d, = 7.8 Hz, 1H, ArH), 6.33 (d, = 7.2 Hz, 1H, CH), 5.26 (s, 1H, CH), 4.88 (s, 1H, CH), 4.73 (d, = 7.2 Hz, 1H, CH), 4.61 (s, 1H, CH), 3.95 (s, 3H, OCH, 3.79 (s, 3H, OCH, 3.44 (s, 3H, OCH, 3.36 (br s, 1H, CH), 3.29 (br s, 1H, CH), 1.38 (s, 3H, CH, 1.06 (brs, 1H, CH), 0.98–0.97 (m, 2H, CH), 0.86 (brs, 1H, CH), 0.71 (br s, 3H, CHC NMR (150 MHz, CDCl : 195.9, 174.1, 165.8, 164.9, 163.3, 145.4, 139.0, 132.6, 130.5, 130.4, 128.0, 127.9, 126.6, 115.5 (d, = 25.2 Hz), 114.9 (d, = 24.3 Hz), 113.6, 113.5, 113.3, 112.1, 110.2, 108.0 (d, = 8.3 Hz), 105.8, 104.7, 63.1, 56.9, 55.4, 54.4, 53.4, 51.7, 47.5, 40.0, 29.4, 29.1, 20.8, 20.5, 20.1, 20.0, 13.7; IR (KBr) : 3449, 2953, 2927, 2867, 2026, 1734, 1700, 1671, 1595, 1490, 1437, 1377, 1313, 1278, 1245, 1200, 1174, 1141, 1120, 1023, 952, 885, 853, 816, 790, 755, 729 cm; MS (/: HRMS (ESI) Calcd. for CHFNO ([M+H]: 589.2358. Found: 589.2366.

Dimethyl 1-butyl-5-chloro-2-(4-methoxybenzoyl)-8- methyl-2-oxo-2,9a-dihydrospiro[indo-line-3,1- quinolizine]-3,4-dicarboxylate ()

Yellow solid, 75 %, m.p. 168–171 C; H NMR (600 MHz, DMSO-: 7.43 (d, = 7.8 Hz, 2H, ArH), 7.29 (d, = 7.8 Hz, 1H, ArH), 7.02 (s, 1H, ArH), 6.90 (t, = 8.4 Hz, 3H, ArH), 6.33 (d, = 7.8 Hz, 1H, CH), 5.27 (s, 1H, CH), 4.89 (s, 1H, CH), 4.73 (d, = 7.2 Hz, 1H, CH), 4.60 (s, 1H, CH), 3.95 (s, 3H, OCH, 3.79 (s, 3H, OCH, 3.44 (s, 3H, OCH, 3.37 (brs, 1H, CH), 3.29–3.26 (m, 1H, CH), 1.38 (s, 3H, CH, 1.05 (br s, 1H, CH), 0.99–0.95 (m, 2H, CH), 0.86 (br s, 1H, CH), 0.71 (t, = 7.2 Hz, 3H, CHC NMR (150 MHz, CDCl : 195.7, 173.9, 165.8, 164.9, 163.3, 145.4, 141.6, 132.7, 130.4, 128.4, 127.9, 127.8, 127.7, 126.5, 113.3, 110.1, 108.5, 106.0, 104.7, 63.2, 55.4, 54.4, 53.4, 51.7, 47.5, 39.9, 29.1, 20.8, 20.0, 13.7; IR (KBr) : 3456, 3071, 2952, 2869, 2587, 2027, 1742, 1710, 1672, 1605, 1579, 1511, 1483, 1432, 1381, 1324, 1243, 1173, 1127, 1045, 1023, 982, 955, 913, 869, 836, 810, 730 cm; MS (/: HRMS (ESI) Calcd. for CHClNO ([M+H]: 605.2062. Found: 605.2067.

Dimethyl 1-benzyl-5-chloro-8-methoxy-2-(4- methoxybenzoyl)-2-oxo-2,9a-dihydrospiro-[indoline-3,1- quinolizine]-3,4-dicarboxylate ()

Yellow solid, 89 %, m.p. 150.0–150.3 C; H NMR (600 MHz, DMSO-: 7.54 (d, = 7.2 Hz, 2H, ArH), 7.25 (d, = 6.6 Hz, 1H, ArH), 7.18 (d, = 6.6 Hz, 1H, ArH), 7.13 (br s, 2H, ArH), 7.01 (s, 1H, ArH), 6.97–6.95 (m, 4H, ArH), 6.82 (d, = 7.8 Hz, 1H, ArH), 6.43 (d, = 7.8 Hz, 1H, CH), 5.36 (s, 1H, CH), 5.05 (s, 1H, CH), 4.66 (d, = 7.2 Hz, 1H, CH), 4.60–4.54 (m, 2H, CH, 3.95 (s, 3H, OCH, 3.82 (s, 3H, OCH, 3.77 (brs, 1H, CH), 3.47 (s, 3H, OCH, 2.93 (s, 3H, OCHC NMR (150 MHz, CDCl: 195.5, 174.5, 165.7, 164.8, 163.5, 153.7, 145.2, 141.4, 135.0, 130.7, 130.6, 130.2, 128.8, 128.6, 128.4, 127.8, 127.7, 127.5, 127.1, 113.5, 113.4, 109.1, 100.2, 83.0, 64.0, 58.4, 55.5, 55.3, 54.1, 53.5, 53.4, 51.9, 47.3, 43.9, 18.4, 15.3; IR (KBr) : 3457, 2954, 1745, 1707, 1671, 1628, 1600, 1511, 1484, 1455, 1435, 1377, 1339, 1251, 1226, 1178, 1136, 979, 944, 902, 868, 845, 808, 757 cm; MS (/: HRMS (ESI) Calcd. for CHClNO ([M+H]: 655.1842. Found: 655.1841.

Dimethyl 1-benzyl-5-chloro-8-methoxy-2-(4- methylbenzoyl)-2-oxo-2,9a-dihydrospiro-[indoline-3,1- quinolizine]-3,4-dicarboxylate ()

Yellow solid, 84 %, m.p. 162.3–163.1 C; H NMR (600 MHz, DMSO-: 7.42 (d, = 7.8 Hz, 2H, ArH), 7.27–7.24 (m, 3H, ArH), 7.18 (d, = 7.2 Hz, 1H, ArH), 7.14 (t, = 7.2 Hz, 2H, ArH), 7.00 (s, 1H, ArH), 6.96 (d, = 7.8 Hz, 2H, ArH), 6.82 (d, = 8.4 Hz, 1H, ArH), 6.43 (d, = 8.4 Hz, 1H, CH), 5.37 (s, 1H, CH), 5.06 (s, 1H, CH), 4.66 (d, = 7.2 Hz, 1H, CH), 4.49 (br s, 2H, CH, 3.95 (s, 3H, OCH, 3.75 (brs, 1H, CH), 3.48 (s, 3H, OCH, 2.91 (s, 3H, OCH, 2.36 (s, 3H, CHC NMR (150 MHz, CDCl: 196.8, 174.4, 173.4, 165.7, 164.8, 153.7, 145.2, 143.7, 141.4, 135.1, 135.0, 134.8, 129.2, 128.9, 128.8, 128.7, 128.5, 128.3, 127.9, 127.8, 127.7, 127.5, 127.3, 126.9, 100.1, 83.0, 63.9, 55.1, 54.0, 53.5, 51.9, 47.8, 43.9, 21.7, 21.6; IR (KBr) : 3455, 2945, 1744, 1716, 1672, 1626, 1600, 1480, 1456, 1432, 1388, 1370, 1317, 1246, 1231, 1175, 1135, 1043, 977, 947, 918, 869, 838, 814, 784 cm; MS (/: HRMS (ESI) Calcd. for CHClNO ([M+H]: 639.1893. Found: 639.1898.

Dimethyl 1-benzyl-5-fluoro-8-methoxy-2-(4- methoxybenzoyl)-2-oxo-2,9a-dihydrospiro-[indoline-3,1- quinolizine]-3,4-dicarboxylate ()

Yellow solid, 91 %, m.p. 147.1–148.0 C; H NMR (600 MHz, DMSO-: 7.54 (d, = 8.4 Hz, 2H, ArH), 7.18 (t, = 7.2 Hz, 1H, ArH), 7.13 (d, = 7.2 Hz, 2H, ArH), 7.04 (t, = 8.4 Hz, 1H, ArH), 6.96 (t, = 7.8 Hz, 4H, ArH), 6.79–6.78 (m, 2H, ArH), 6.43 (d, = 7.8 Hz, 1H, CH), 5.35 (s, 1H, CH), 5.04 (d, = 3.0 Hz, 1H, CH), 4.65 (d, = 6.6 Hz, 1H, CH), 4.56 (brs, 2H, CH, 3.95 (s, 3H, OCH, 3.83 (s, 3H, OCH, 3.78 (br s, 1H, CH), 3.47 (s, 3H, OCH, 2.93 (s, 3H, OCHC NMR (150 MHz, DMSO-: 195.3, 173.6, 165.0, 164.0, 163.3, 157.9 (d, = 236.9 Hz), 153.0, 144.8, 139.1, 135.6, 130.2, 129.6, 129.3, 128.5, 127.4, 127.3, 127.2, 115.1 (d, = 23.1 Hz), 114.3 (d, = 28.2 Hz), 113.6, 109.4 (d, = 6.2 Hz), 106.1, 99.7, 82.8, 63.3, 56.0, 55.5, 54.5, 53.8, 53.4, 51.6, 46.4, 43.0, 18.5; IR (KBr) : 3450, 1737, 1641, 1488, 1422, 1369, 1285, 1232, 1187, 1111, 952, 865, 816, 774 cm; MS (/: HRMS (ESI) Calcd. for CHFNO ([M+H]: 639.2137. Found: 639.2142.

Dimethyl 1-benzyl-5-fluoro-8-methoxy-2-(4-methylbenzoyl)-2-oxo-2,9a-dihydrospiro[indo line-3,1-quinolizine]-3,4-dicarboxylate ()

Yellow solid, 87 %, m.p. 158.5–159.0 C; H NMR (600 MHz, DMSO-: 7.42 (d, = 7.8 Hz, 2H, ArH), 7.24 (t, = 7.8 Hz, 2H, ArH), 7.18 (t, = 7.2 Hz, 1H, ArH), 7.14 (t, = 7.2 Hz, 2H, ArH), 7.06 (t, = 8.4 Hz, 1H, ArH), 6.97 (t, = 7.2 Hz, 2H, ArH), 6.81–6.77 (m, 2H, ArH), 6.43 (d, = 8.4 Hz, 1H, CH), 5.37 (s, 1H, CH), 5.05 (d, = 8.4 Hz, 1H, CH), 4.66 (d, = 7.8 Hz, 1H, CH), 4.48 (brs, 2H, CH, 3.95 (s, 3H, OCH, 3.76 (brs, 1H, CH), 3.48 (s, 3H, OCH, 2.91 (s, 3H, OCH, 2.36 (s, 3H, CHC NMR (150 MHz, CDCl: 196.9, 174.6, 165.7, 164.8, 159.0 (d, = 240 Hz), 153.6, 145.2, 143.7, 138.8, 135.2 134.8, 128.9, 128.8, 128.3, 127.7, 115.4 (d, = 25.4 Hz), 115.1 (d, = 23.4 Hz), 108.7 (d, = 7.5 Hz), 106.5, 100.2, 83.1, 63.9, 55.2, 54.1, 53.5, 51.8, 47.7, 43.9, 21.6; IR (KBr) : 3454, 2946, 1745, 1715, 1675, 1625, 1597, 1487, 1454, 1434, 1387, 1317, 1297, 1243, 1227, 1179, 1153, 1128, 1045, 981, 947, 892, 868, 843, 809, 767 cm; MS (/: HRMS (ESI) Calcd. for CHFNO ([M+H]: 623.2188. Found: 623.2190.

Dimethyl 1-benzyl-5-fluoro-8-methoxy-2-benzoyl-2-oxo- 2,9a-dihydrospiro[indoline-3,1-quinolizine]-3,4- dicarboxylate ()

Yellow solid, 81 %, m.p. 137.2–137.6 C; H NMR (600 MHz, DMSO-: 7.63 (brs, 1H, ArH), 7.46–7.44 (m, 4H, ArH), 7.17 (brs, 3H, ArH), 7.08 (brs, 1H, ArH), 7.02 (brs, 2H, ArH), 6.83–6.77 (m, 2H, ArH), 6.44 (d, = 8.4 Hz, 1H, CH), 5.39 (s, 1H, CH), 5.06 (brs, 1H, CH), 4.66 (d, = 5.4 Hz, 1H, CH), 4.46 (d, = 15.0 Hz, 1H, CH), 4.36 (d, = 15.0 Hz, 1H, CH), 3.96 (s, 3H, OCH, 3.75 (br s, 1H, CH), 3.50 (s, 3H, OCH, 2.88 (s, 3H, OCHC NMR (150 MHz, CDCl: 197.5, 174.5, 165.7, 164.7, 159.0 (d, = 239.9 Hz), 153.6, 145.2, 138.9, 137.5, 135.3, 132.9, 128.8, 128.7, 128.2, 128.1, 127.8, 127.6, 115.4 (d, = 21.2 Hz), 115.2 (d, = 19.7 Hz), 108.7 (d, = 8.4 Hz), 106.3, 100.3, 83.1, 63.8, 55.1, 54.0, 53.5, 51.9, 48.1, 43.9; IR (KBr) : 3450, 2948, 1752, 1712, 1647, 1631, 1598, 1488, 1436, 1388, 1335, 1296, 1227, 1155, 1131, 1051, 980, 940, 908, 894, 862, 826, 768 cm; MS (/: HRMS (ESI) Calcd. for CHFNO ([M+H]: 609.2032. Found: 609.2034.

Dimethyl 1-butyl-5-chloro-8-methoxy-2-(4- methylbenzoyl)-2-oxo-2,9a-dihydrospiro[indo-line-3,1- quinolizine]-3,4-dicarboxylate ()

Yellow solid, 93 %, m.p. 162.1–163.0 C; H NMR (600 MHz, DMSO-: 7.41 (d, = 8.4 Hz, 2H, ArH), 7.30 (dd, = 8.4 Hz, = 1.8 Hz, 1H, ArH), 6.98 (d, = 1.8 Hz, 1H, ArH), 6.90 (dd, = 5.7 Hz, = 3.0 Hz, 3H, ArH), 6.43 (d, = 7.8 Hz, 1H, CH), 5.26 (s, 1H, CH), 4.98 (d, = 3.0 Hz, 1H, CH), 4.70 (dd, = 7.8 Hz, = 1.8 Hz, 1H, CH), 3.95 (s, 3H, OCH, 3.85 (br s, 1H, CH), 3.79 (s, 3H, OCH, 3.47 (s, 3H, OCH, 3.38–3.33 (m, 1H, CH), 3.30–3.27 (m, 1H, CH), 3.18 (s, 3H, OCH, 1.10–1.05 (m, 1H, CH), 1.00–0.96 (m, 2H, CH), 0.94–0.89 (m, 1H, CH), 0.71 (t, = 7.2 Hz, 3H, CHC NMR (150 MHz, CDCl: 195.7, 174.1, 165.7, 164.8, 163.3, 163.2, 153.6, 145.2, 141.8, 130.4, 128.8, 128.6, 128.0, 127.7, 125.8, 113.6, 113.3, 108.4, 106.8, 102.5, 100.1, 83.1, 63.7, 57.6, 55.4, 55.2, 54.1, 53.4, 51.8, 47.5, 39.9, 29.3, 20.1, 13.6; IR (KBr) : 3450, 2953, 1737, 1713, 1670, 1626, 1601, 1574, 1510, 1483, 1459, 1432, 1384, 1323, 1246, 1175, 1133, 1116, 1027, 979, 940, 915, 873, 848, 812, 780 cm; MS (/: HRMS (ESI) Calcd. for CHClNO ([M+H]: 621.1998. Found: 621.1997.

Dimethyl 1-butyl-5-fluoro-8-methoxy-2-(4- methylbenzoyl)-2-oxo-2,9a-dihydrospiro[indo-line-3,1- quinolizine]-3,4-dicarboxylate ()

Yellow solid, 90 %, m.p. 176.7–177.2 C; H NMR (600 MHz, DMSO-: 7.28 (d, = 8.4 Hz, 2H, ArH), 7.17 (d, = 7.8 Hz, 2H, ArH), 7.10 (td, = 9.0 Hz, = 2.4 Hz, 1H, ArH), 6.87 (dd, = 8.4 Hz, = 4.2 Hz, 1H, ArH), 6.75 (dd, = 8.4 Hz, = 2.4 Hz, 1H, ArH), 6.43 (d, = 7.8 Hz, 1H, CH), 5.27 (s, 1H, CH), 4.97 (d, = 3.6 Hz, 1H, CH), 4.70 (dd, = 8.4 Hz, = 2.4 Hz, 1H, CH), 3.95 (s, 3H, OCH, 3.86 (br s, 1H, CH), 3.48 (s, 3H, OCH, 3.30–3.20 (m, 2H, CH), 3.18 (s, 3H, OCH, 2.31 (s, 3H, CH, 1.09–1.03 (m, 1H, CH), 1.02–0.97 (m, 2H, CH), 0.92–0.85 (m, 1H, CH), 0.72 (t, = 7.2 Hz, 3H, CHC NMR (150 MHz, CDCl: 197.2, 174.1, 165.7, 164.8, 158.9 (d, = 239.4 Hz), 153.5, 145.2, 143.5, 139.2, 135.0, 129.1, 128.8, 128.3, 128.1, 115.4 (d, = 25.1 Hz), 107.9 (d, = 8.3 Hz), 106.6, 102.6, 100.2, 83.2, 63.6, 57.6, 55.1, 54.1, 53.4, 51.8, 47.8, 39.9, 29.2, 21.6, 20.1, 13.7; IR (KBr) : 3452, 2951, 1751, 1709, 1676, 1629, 1599, 1491, 1456, 1437, 1378, 1322, 1275, 1229, 1197, 1181, 1159, 1134, 1048, 1005, 975, 940, 901, 868, 839, 823, 761 cm; MS (/: HRMS (ESI) Calcd. for CHFNO ([M+H]: 589.2345. Found: 589.2345.

Dimethyl 1-benzyl-2-(4-methylbenzoyl)-2,8-dioxo- 2,8,9,9a-tetrahydrospiro[indoline-3,1-quinolizine]-3,4- dicarboxylate ()

White solid, m.p. 188.8–188.9 C; H NMR (600 MHz, DMSO-: 7.59 (br s, 2H, ArH), 7.36 (br s, 1H, ArH), 7.19–7.13 (m, 8H, ArH), 6.80 (br s, 2H, ArH), 6.56 (brs, 1H, CH), 5.28 (br s, 2H, CH), 4.46 (d, = 13.2 Hz, 1H, CH), 4.39 (d, = 15.6 Hz, 1H, CH), 4.29 (d, = 15.6 Hz, 1H, CH), 4.06 (s, 3H, OCH, 3.51 (s, 3H, OCH, 2.40 (s, 3H, CH, 2.22 (d, = 15.6 Hz, 1H, CH), 1.89 (t, = 15.6 Hz, 1H, CH); C NMR (150 MHz, CDCl: 195.4, 190.3, 174.3, 165.3, 164.0, 144.4, 142.7, 134.6, 134.0, 129.6, 129.2, 128.8, 128.6, 127.7, 127.1, 127.0, 124.2, 123.9, 109.6, 107.3, 106.0, 59.0, 53.8, 52.0, 51.8, 45.9, 44.2, 36.1, 21.7; IR (KBr) : 3453, 1752, 1715, 1664, 1637, 1593, 1487, 1466, 1453, 1367, 1326, 1292, 1254, 1218, 1183, 1129, 1106, 945, 904, 795, 754 cm; MS (/: HRMS (ESI) Calcd. for CHNNaO ([M+Na]: 613.1945. Found: 613.1947.

Dimethyl 1-benzyl-5-chloro-2-(4-methylbenzoyl)-2,8-dioxo-2,8,9,9a-tetrahydrospiro[indo line-3,1-quinolizine]-3,4-dicarboxylate ()

White solid, m.p. 181.1–181.3 C; H NMR (600 MHz, DMSO-: 7.89 (br s, 2H, ArH), 7.59 (br s, 1H, ArH), 7.47 (br s, 1H, ArH), 7.29 (br s, 5H, ArH), 7.13 (br s, 4H, ArH, CH), 5.34 (s, 1H, CH), 4.91 (brs, 2H, CH), 4.66–4.63 (m, 2H, CH), 3.99 (s, 3H, OCH, 3.47 (s, 3H, OCH, 2.38 (s, 3H, CH, 1.87 (br s, 2H, CH); C NMR (150 MHz, CDCl: 197.6, 190.3, 172.4, 164.9, 164.0, 144.7, 144.2, 144.0, 141.0, 135.1, 134.7, 129.8, 129.6, 129.4, 128.9, 128.7, 128.1, 127.6, 125.5, 110.7, 107.7, 102.6, 54.9, 53.8, 52.3, 51.0, 44.2, 43.3, 36.3, 21.7; IR (KBr) : 3452, 2956, 1740, 1713, 1678, 1633, 1594, 1479, 1439, 1383, 1326, 1300, 1249, 1186, 1131, 1081, 1002, 956, 936, 898, 883, 855, 815, 781, 737, 704 cm; MS (/: HRMS (ESI) Calcd. for CHClNO ([M+H]: 625.1736. Found: 625.1745.

General procedure for the three-component reaction of quinoline, DMAD, and 3-methyleneoxindoles

A mixture of quinoline (1.5 mmol), DMAD (1.5 mmol, 0.213 g), and 3-methyleneoxindole (1.0 mmol) in 10.0 mL of dimethoxyethane (DME) was stirred at room temperature for 6 h. Then, the solvent was removed by evaporation and the residue was quickly subjected to thin-layer chromatography (15 25 cm SiO plate) with a mixture of light petroleum and ethyl acetate (V/V = 2:1) as the developing reagent.

Dimethyl 1-benzyl-5-chloro-3-(4-methylbenzoyl)-2-oxo- 3,4a-dihydrospiro[indoline-3,4-pyrido[1,2-a]quinoline]- 1,2-dicarboxylate ()

Yellow solid, 40 %, m.p. 183–186 C; H NMR (600 MHz, DMSO-: 7.36 (br s, 2H, ArH), 7.23 (b rs, 2H, ArH), 7.16 (br s, 4H, ArH), 6.98–6.93 (m, 2H, ArH), 6.86 (br s, 4H, ArH), 6.65 (br s, 1H, ArH), 6.57 (br s, 1H, ArH), 6.33 (d, = 5.4 Hz, 1H, CH), 5.42 (s, 1H, CH), 5.33 (brs, 1H, CH), 4.72–4.61 (br s, 3H, CH), 3.88 (s, 3H, OCH, 3.61 (s, 3H, OCH, 2.33 (s, 3H, CHC NMR (150 MHz, CDCl: 195.4, 173.8, 166.0, 165.2, 146.1, 143.7, 141.5, 138.1, 134.7, 134.6, 129.9, 129.2, 129.1, 128.7, 128.5, 128.4, 128.1, 127.8, 127.7, 126.9, 126.7, 122.4, 121.6, 118.9, 118.0, 114.7, 109.2, 65.0, 59.3, 53.1, 52.3, 49.4, 44.1; IR (KBr) : 3448, 2949, 1721, 1701, 1683, 1640, 1571, 1490, 1432, 1382, 1356, 1302, 1242, 1179, 1114, 972, 817 cm; MS (/: HRMS (ESI) Calcd. for CHClNO ([M+H]: 659.1943. Found: 659.1941.

Dimethyl 1-benzyl-5-chloro-3-(4-chlorobenzoyl)-2-oxo- 3,4a-dihydrospiro[indoline-3,4-pyrido[1,2-a]quinoline]- 1,2-dicarboxylate ()

Yellow solid, 52 %, m.p. 171–173 C; H NMR (600 MHz, DMSO-: 7.45 (br s, 4H, ArH), 7.22 (br s, 4H, ArH), 7.02 (br s, 1H, ArH), 6.87 (brs, 5H, ArH), 6.66 (br s, 2H, ArH), 6.35 (br s, 1H, CH), 5.45 (br s, 1H, CH), 5.34 (br s, 1H, CH), 4.76–4.64 (m, 3H, CH), 3.89 (s, 3H, OCH, 3.62 (s, 3H, OCHC NMR (150 MHz, DMSO-: 194.8, 172.6, 165.4, 164.4, 150.5, 144.9, 141.7, 138.6, 137.5, 135.9, 135.2, 135.0, 129.8, 129.5, 128.9, 128.5, 128.3, 128.1, 128.0, 127.9, 127.4, 127.0, 126.1, 125.8, 122.4, 121.4, 118.6, 118.3, 113.9, 110.1, 64.3, 58.0, 53.1, 48.7, 43.2; IR (KBr) : 3448, 2949, 1722, 1702, 1641, 1614, 1490, 1433, 1401, 1382, 1356, 1304, 1241, 1190, 1130, 1090, 1015, 968, 917, 850, 817 cm; MS (/: HRMS (ESI) Calcd. for CHClNO ([M+H]: 679.1397. Found: 679.1392.

Dimethyl 1-benzyl-5-fluoro-3-benzoyl-2-oxo-3,4a- dihydrospiro[indoline-3,4-pyrido[1,2-a]-quinoline]-1,2- dicarboxylate ()

Yellow solid, 55 %, m.p. 166–167 C; H NMR (600 MHz, DMSO-: 7.58 (br s, 1H, ArH), 7.41–7.36 (m, 4H, ArH), 7.21 (br s, 4H, ArH), 6.95–6.80 (m, 6H, ArH), 6.56 (br s, 1H, ArH), 6.41–6.40 (m, 1H, ArH), 6.34–6.33 (m, 1H, CH), 5.44 (s, 1H, CH), 5.32 (d, = 6.6 Hz, 1H, CH), 4.68–4.61 (m, 3H, CH), 3.89 (s, 3H, OCH, 3.63 (s, 3H, OCHC NMR (150 MHz, DMSO- : 195.8, 172.9, 165.5, 164.5, 157.2 (d, = 236.4 Hz), 150.5, 145.0, 139.3, 137.5, 136.5, 136.0, 135.3, 133.4, 129.8, 128.6, 127.9, 127.8, 127.6, 127.4, 126.9, 126.2 (d, = 8.7 Hz), 122.3, 121.4, 118.7, 118.5, 115.5 (d, = 25.7 Hz), 114.8 (d, = 23.0 Hz), 113.9, 109.5 (d, = 8.3 Hz), 64.3, 58.4, 53.1, 52.3, 48.9, 43.3; IR (KBr) : 3448, 2952, 1737, 1711, 1633, 1605, 1571, 1491, 1437, 1407, 1383, 1360, 1180, 1114, 1081, 1014, 967, 875, 819, 768 cm; MS (/: HRMS (ESI) Calcd. for CHFNO ([M+H]: 629.2082. Found: 629.2078.

Dimethyl 1-benzyl-5-fluoro-3-(4-chlorobenzoyl)-2-oxo- 3,4a-dihydrospiro[indoline-3,4-pyrido[1,2-a]quinoline]- 1,2-dicarboxylate ()

Yellow solid, 53 %, m.p. 170–171 C; H NMR (600 MHz, DMSO-: 7.45 (br s, 4H, ArH), 7.22 (br s, 4H, ArH), 6.90 (br s, 6H, ArH), 6.65 (br s, 1H, ArH), 6.42–6.35 (m, 2H, ArH, CH), 5.44 (s, 1H, CH), 5.35 (brs, 1H, CH), 4.76–4.65 (m, 3H, CH), 3.88 (s, 3H, OCH, 3.62 (s, 3H, OCHC NMR (150 MHz, DMSO- : 194.8, 172.8, 165.5, 164.4, 157.3 (d, = 239.1 Hz), 144.9, 139.2, 138.5, 137.5, 135.3, 135.1, 129.8, 129.5, 128.9, 128.5, 127.9, 127.8, 127.4, 127.0, 126.0 (d, = 9.2 Hz), 122.4, 121.5, 118.5, 115.6 (d, = 17.0 Hz), 115.0 (d, = 18.6 Hz), 113.9, 109.6, 64.3, 58.1, 53.1, 52.3, 48.7, 43.3; IR (KBr) : 3450, 2949, 1712, 1634, 1570, 1491, 1454, 1431, 1405, 1382, 1351, 1245, 1178, 1092, 967, 852, 820, 776 cm; MS (/: HRMS (ESI) Calcd. for CHClFNO ([M+H]: 663.1693. Found: 663.1692.

Dimethyl 1-butyl-5-chloro-3-(4-methoxybenzoyl)-2-oxo- 3,4a-dihydrospiro[indoline-3,4-pyrido[1,2-a]quinoline]- 1,2-dicarboxylate ()

Yellow solid, 60 %, m.p. 186–189 C; H NMR (600 MHz, DMSO-: 7.34 (br s, 2H, ArH), 7.22 (br s, 1H, ArH), 7.05 (br s, 1H, ArH), 6.93 (brs, 1H, ArH), 6.87 (br s, 4H, ArH), 6.76 (br s, 1H, ArH), 6.62 (br s, 1H, ArH), 6.35 (br s, 1H, CH), 5.44 (s, 1H, CH), 5.32–5.29 (m, 2H, CH), 4.59 (s, 1H, CH), 3.88 (s, 3H, OCH, 3.76 (s, 3H, OCH, 3.61 (s, 3H, OCH, 3.44 (brs, 2H, CH), 1.03–1.02 (m, 4H, CH), 0.76 (brs, 3H, CHC NMR (150 MHz, DMSO- : 194.1, 172.5, 165.5, 164.6, 163.2, 144.9, 142.2, 137.6, 129.9, 129.8, 129.5, 128.1, 128.0, 127.8, 126.5, 125.3, 122.2, 121.4, 118.9, 118.4, 113.8, 113.7, 109.4, 64.0, 58.3, 55.4, 53.0, 52.2, 48.9, 28.7, 19.4, 13.5; IR (KBr) : 3452, 2947, 1739, 1716, 1680, 1603, 1572, 1490, 1434, 1381, 1355, 1309, 1252, 1210, 1179, 1135, 1022, 968, 883, 816, 779 cm; MS (/: HRMS (ESI) Calcd. for CHClNO ([M+H]: 641.2049. Found: 649.2045.

3-Ethyl 1,2-dimethyl 1-benzyl-5-methyl-2-oxo- 3,4a-dihydrospiro[indoline-3,4-pyrido-[1,2-a]quinoline]- 1,2,3-tricarboxylate ()

Yellow solid, 50 %, m.p. 117–115 C; H NMR (600 MHz, DMSO-: 7.38–7.18 (m, 6H, ArH), 6.94–6.82 (m, 5H, ArH), 6.52 (br s, 1H, ArH), 6.29 (br s, 1H, CH), 5.35 (b rs, 1H, CH), 5.02 (br s, 1H, CH), 4.88 (br s, 1H, CH), 4.50 (s, 1H, CH), 4.26 (s, 1H, CH), 3.87 (s, 3H, OCH, 3.70 (s, 3H, OCH, 3.35–3.54 (m, 2H, CH, 1.74 (s, 3H, CH, 0.38–0.37 (m, 3H, CHC NMR (150 MHz, DMSO-: 173.2, 168.1, 165.3, 164.7, 144.8, 141.1, 137.7, 136.1, 130.0, 129.4, 128.7, 128.5, 127.8, 127.6, 127.5, 127.4, 124.6, 122.1, 121.5, 118.9, 115.8, 114.0, 108.4, 63.9, 60.2, 58.2, 53.0, 52.2, 47.0, 43.3, 20.0, 12.8; IR (KBr) : 3452, 2951, 1742, 1709, 1604, 1572, 1496, 1457, 1435, 1381, 1352, 1307, 1253, 1218, 1184, 1161, 1119, 1088, 1019, 981, 810, 776 cm; MS (/: HRMS (ESI) Calcd. for CHNO ([M+H]: 593.2282. Found: 593.2285.

3-Ethyl 1,2-dimethyl 1-benzyl-2-oxo-3,4a- dihydrospiro[indoline-3,4-pyrido[1,2-a]quino-line]- 1,2,3-tricarboxylate ()

Yellow solid, 63 %, m.p. 176–177 C; H NMR (600 MHz, DMSO-: 7.42–7.37 (m, 4H, ArH), 7.30 (br s, 1H, ArH), 7.17 (br s, 1H, ArH), 7.05 (brs, 1H, ArH), 6.92 (br s, 2H, ArH), 6.85–6.82 (m, 2H, ArH), 6.69 (br s, 1H, ArH), 6.52 (br s, 1H, ArH), 6.32 (br s, 1H, CH), 5.38 (br s, 1H, CH), 5.06 (d, = 15.0 Hz, 1H, CH), 4.90 (d, = 15.0 Hz, 1H, CH), 4.56 (s, 1H, CH), 4.28 (s, 1H, CH), 3.86 (s, 3H, OCH, 3.70 (s, 3H, OCH, 3.53 (br s, 1H, CH), 3.48 (brs, 1H, CH), 0.33 (brs, 3H, CHC NMR (150 MHz, DMSO-: 173.4, 168.1, 165.3, 164.6, 145.0, 143.6, 137.3, 136.0, 129.6, 128.8, 128.5, 127.7, 127.6, 127.5, 126.5, 124.7, 122.3, 121.4, 121.1, 118.9, 115.3, 113.9, 109.0, 64.1, 60.3, 58.0, 53.0, 52.2, 48.0, 43.3, 12.8; IR (KBr) : 3452, 2950, 1740, 1707, 1610, 1571, 1493, 1463, 1435, 1384, 1357, 1307, 1282, 1252, 1221, 1177, 1132, 1087, 1020, 981, 902, 875, 831, 813, 783 cm; MS (/: HRMS (ESI) Calcd. for CHNO ([M+H]: 579.2126. Found: 579.2131.

3-Ethyl 1,2-dimethyl 1-benzyl-5-chloro-2-oxo- 3,4a-dihydrospiro[indoline-3,4-pyrido-[1,2-a]quinoline]- 1,2,3-tricarboxylate ()

Yellow solid, 70 %, m.p. 173–174 C; H NMR (600 MHz, DMSO-: 7.39–7.36 (m, 4H, ArH), 7.31–7.30 (m, 1H, ArH), 7.20 (t, = 7.8 Hz, 1H, ArH), 7.13 (d, = 8.4 Hz, 1H, ArH), 6.95–6.90 (m, 3H, ArH), 6.84 (d, = 7.2 Hz, 1H, ArH), 6.60 (brs, 1H, ArH), 6.35 (d, = 9.6 Hz, 1H, CH), 5.37 (dd, = 9.6 Hz, = 3.6 Hz, 1H, CH), 5.07 (d, = 15.6 Hz, 1H, CH), 4.90 (d, = 15.6 Hz, 1H, CH), 4.58 (s, 1H, CH), 4.29 (s, 1H, CH), 3.87 (s, 3H, OCH, 3.71 (s, 3H, OCH, 3.61–3.56 (m, 2H, CH, 0.42 (t, = 7.2 Hz, 3H, CHC NMR (150 MHz, DMSO-: 172.9, 168.1, 165.2, 164.5, 144.6, 142.4, 137.3, 135.7, 129.8, 128.6, 128.0, 127.7, 127.6, 126.9, 126.5, 125.5, 122.4, 121.3, 118.5, 115.7, 113.7, 110.3, 63.7, 60.5, 58.3, 53.1, 52.3, 47.8, 43.4, 12.8; IR (KBr) : 3448, 2949, 1735, 1712, 1603, 1570, 1493, 1457, 1434, 1364, 1341, 1311, 1250, 1212, 1179, 1140, 1087, 1016, 977, 812, 775 cm; MS (/: HRMS (ESI) Calcd. for CHClNO ([M+H]: 613.1736. Found: 613.1739.

3-Ethyl 1,2-dimethyl 1-butyl-5-chloro-2-oxo-3,4a-dihydrospiro[indoline-3,4-pyrido[1,2-a] quinoline]-1,2,3-tricarboxylate ()

Yellow solid, 73 %, m.p. 158–159 C; H NMR (600 MHz, DMSO-: 7.20–7.18 (m, 2H, ArH), 7.05 (d, = 7.8 Hz, 1H, ArH), 6.92–6.91 (m, 2H, ArH), 6.86–6.85 (m, 1H, ArH), 6.65 (br s, 1H, ArH), 6.38 (d, = 9.6 Hz, 1H, CH), 5.37 (d, = 6.6 Hz, 1H, CH), 4.52 (s, 1H, CH), 4.21 (s, 1H, CH), 3.87 (s, 3H, OCH, 3.74 (br s, 2H, CH, 3.69 (s, 3H, OCH, 3.63–3.62 (m, 2H, CH, 1.57 (brs, 2H, CH, 1.35–1.34 (m, 2H, CH, 0.93 (br s, 3H, CH, 0.61 (brs, 3H, CHC NMR (150 MHz, DMSO-: 172.6, 172.6, 168.1, 165.2, 164.5, 144.6, 142.8, 137.4, 129.8, 128.6, 127.9, 127.6, 126.9, 126.6, 125.2, 122.4, 121.3, 118.5, 115.6, 113.8, 109.9, 63.5, 60.4, 58.2, 53.0, 52.2, 47.9, 29.0, 19.4, 13.5, 13.1; IR (KBr) : 3454, 2956, 1744, 1713, 1639, 1614, 1598, 1570, 1490, 1433, 1378, 1355, 1325, 1303, 1247, 1212, 1183, 1135, 1116, 1021, 989, 969, 944, 914, 868, 822, 780 cm; MS (/: HRMS (ESI) Calcd. for CHClNO ([M+H]: 579.1893. Found: 579.1894.

3-Ethyl 1,2-dimethyl 1-benzyl-5-fluoro-2-oxo-3,4a- dihydrospiro[indoline-3,4-pyrido-[1,2-a]quinoline]- 1,2,3-tricarboxylate ()

Yellow solid, 65 %, m.p. 160–163 C; H NMR (600 MHz, DMSO-: 7.40–7.37 (m, 4H, ArH), 7.30 (br s, 1H, ArH), 7.20 (br s, 1H, ArH), 7.94–7.63 (m, 4H, ArH), 6.85 (br s, 1H, ArH), 6.43 (br s, 1H, ArH), 6.36 (d, = 8.4 Hz, 1H, CH), 5.40 (br s, 1H, CH), 5.08 (d, = 15.6 Hz, 1H, CH), 4.90 (d, = 15.6 Hz, 1H, CH), 4.60 (s, 1H, CH), 4.30 (s, 1H, CH), 3.87 (s, 3H, OCH, 3.70 (s, 3H, OCH, 3.59–3.55 (m, 2H, CH, 0.38 (brs, 3H, CHC NMR (150 MHz, CDCl: 174.0, 168.6, 165.8, 165.1, 158.1 (d, = 239.6 Hz), 145.6, 139.7, 137.9, 135.3, 129.8, 128.8, 128.2, 128.0, 127.9, 127.6, 127.1 (d, = 7.8 Hz), 122.5, 121.6, 118.3, 115.9, 115.6 (d, = 26.0 Hz), 115.0 (d, = 23.3 Hz), 114.4, 109.0 (d, = 8.0 Hz), 64.5, 60.9, 59.3, 53.1, 52.2, 48.4, 44.4, 13.3; IR (KBr) : 3451, 2950, 1739, 1708, 1608, 1571, 1494, 1456, 1436, 1344, 1307, 1252, 1226, 1175, 1131, 1020, 979, 900, 875, 827, 775 cm; MS (/: HRMS (ESI) Calcd. for CHFNO ([M+H]: 597.2032. Found: 597.2034.

General procedure for the Diels–Alder reaction of spiro[indoline-3,1-quinolizines]

A mixture of spiro[indoline-3,1-quinolizine] (1.0 mmol) and -substituted maleimide or maleic anhydride (1.5 mmol) in 10.0 mL of DME was refluxed for 12 h. Then, the solvent was removed by evaporation and the residue was subjected to thin-layer chromatography with a mixture of light petroleum and ethyl acetate (V/V = 2:1) as the developing reagent to give the pure spiro compound 4a–4g.

Spiro compounds ()

White solid, 80 %, m.p. 297–298 C; H NMR (600 MHz, DMSO-: 7.60 (d, = 8.4 Hz, 2H, ArH), 7.44 (t, = 7.8 Hz, 2H, ArH), 7.38 (t, = 7.2 Hz, 1H, ArH), 7.19 (t, = 7.2 Hz, 1H, ArH), 7.14 (t, = 7.2 Hz, 2H, ArH), 7.05 (t, = 8.4 Hz, 1H, ArH), 6.99–6.97 (m, 6H, ArH), 6.79 (dd, = 9.0 Hz, = 4.2 Hz, 1H, ArH), 6.61–6.60 (m, 1H, ArH), 5.77 (d, = 5.4 Hz, 1H, CH), 5.20 (s, 1H, CH), 4.59 (br s, 2H, CH, 4.32–4.31 (m, 1H, CH), 4.15 (s, 1H, CH), 4.00 (s, 3H, OCH, 3.84 (s, 3H, OCH, 3.54 (dd, = 7.5 Hz, = 3.0 Hz, 1H, CH), 3.48 (dd, = 7.5 Hz, = 3.0 Hz, 1H, CH), 3.34 (br s, 3H, OCH, 2.66 (s, 1H, CH), 0.52 (s, 3H, CHC NMR (150 MHz, DMSO-: 194.6, 175.1, 174.5, 174.1, 165.3, 164.5, 163.1, 157.7 (d, = 236.4 Hz), 146.5, 140.6, 138.5, 135.6, 131.8, 130.1, 129.8, 129.0, 128.6, 128.5, 127.5, 127.4, 126.6, 126.0 (d, = 9.5 Hz), 122.6, 117.2 (d, = 24.8 Hz), 114.6 (d, = 23.6 Hz), 113.5, 109.8 (d, = 7.2 Hz), 94.6, 60.7, 55.5, 53.3, 51.9, 50.8, 49.8, 45.9, 43.1, 42.2, 38.5, 18.9; IR (KBr) : 3450, 2951, 1778, 1711, 1670, 1590, 1488, 1459, 1434, 1376, 1345, 1324, 1244, 1176, 1123, 1033, 987, 950, 903, 843, 811 cm; MS (/: HRMS (ESI) Calcd. for CHFNO ([M+H]: 796.2665. Found: 796.2670. White solid, 77 %, m.p. 300 C; H NMR (600 MHz, DMSO-: 7.49 (d, = 7.8 Hz, 2H, ArH), 7.43 (t, = 7.8 Hz, 2H, ArH), 7.38 (t, = 7.8 Hz, 1H, ArH), 7.26–7.25 (m, 3H, ArH), 7.19 (t, = 7.2 Hz, 1H, ArH), 7.14 (t, = 7.2 Hz, 2H, ArH), 7.00–6.99 (m, 4H, ArH), 6.83–6.82 (m, 2H, ArH), 5.74 (d, = 5.4 Hz, 1H, CH), 5.21 (s, 1H, CH), 4.54 (br s, 2H, CH, 4.32–4.30 (m, 1H, CH), 4.15 (s, 1H, CH), 4.00 (s, 3H, OCH, 3.54 (dd, = 7.5 Hz, = 3.0 Hz, 1H, CH), 3.47 (dd, = 7.5 Hz, = 3.0 Hz, 1H, CH), 3.35 (s, 3H, OCH, 2.64 (s, 1H, CH), 2.37 (s, 3H, CH, 0.50 (s, 3H, CHC NMR (150 MHz, CDCl: 196.0, 175.0, 174.7, 173.8, 166.0, 165.1, 146.8, 143.7, 141.7, 140.9, 135.0, 134.7, 131.3, 131.1, 129.3, 129.0, 128.9, 128.4, 128.3, 128.0, 127.4, 126.6, 126.1, 109.8, 96.5, 61.6, 53.7, 52.1, 51.3, 50.4, 46.0, 44.2, 42.6, 39.2, 21.6, 19.4; IR (KBr) : 3452, 2952, 1781, 1712, 1641, 1483, 1430, 1384, 1322, 1233, 1186, 1129, 949, 887, 803 cm; MS (/: HRMS (ESI) Calcd. for CHClNO ([M+H]: 796.2420. Found: 796.2429. White solid, 72 %, m.p. 173–175 C; H NMR (600 MHz, DMSO-: 7.46 (d, = 8.4 Hz, 2H, ArH), 7.22 (d, = 7.8 Hz, 2H, ArH), 7.09 (t, = 8.4 Hz, 1H, ArH), 6.91–6.86 (m, 5H, ArH), 6.57 (d, = 6.6 Hz, 1H, ArH), 5.81 (d, = 4.2 Hz, 1H, CH), 5.09 (s, 1H, CH), 4.31 (br s, 1H, CH), 4.04 (s, 1H, CH), 4.00 (s, 3H, OCH, 3.80 (s, 3H, OCH, 3.53–3.52 (m, 1H, CH), 3.46–3.45 (m, 1H, CH), 3.37 (brs, 1H, CH), 3.28 (s, 3H, OCH, 3.26 (br s, 1H, CH), 2.61 (s, 1H, CH), 2.29 (s, 3H, CH, 1.04–1.01 (m, 3H, CH), 0.84–0.82 (m, 1H, CH), 0.74–0.71 (m, 6H, CHC NMR (150 MHz, DMSO-: 196.1, 173.7, 170.9, 169.5, 165.3, 164.5, 157.2 (d, = 235.2 Hz), 146.3, 143.3, 139.3, 134.6, 138.7, 127.7, 124.5 (d, = 8.9 Hz), 116.4 (d, = 25.2 Hz), 114.8 (d, = 23.1 Hz), 109.3 (d, = 8.9 Hz), 95.1, 93.6, 58.4, 55.1, 53.4, 51.6, 50.9, 49.9, 47.8, 47.5, 43.0, 37.5, 28.5, 21.0, 19.2, 13.5; IR (KBr) : 3457, 2956, 1712, 1600, 1514, 1489, 1455, 1386, 1322, 1237, 1178, 1131, 1025, 962, 808, 758 cm; MS (/: HRMS (ESI) Calcd. for CHFNNaO ([M+Na]: 798.2797. Found: 798.2783. White solid, 85 %, m.p. 182–185 C; H NMR (600 MHz, DMSO-: 7.51 (d, = 8.4 Hz, 2H, ArH), 7.46 (d, = 8.4 Hz, 2H, ArH), 7.11–7.08 (m, 1H, ArH), 7.05 (d, = 8.4 Hz, 2H, ArH), 6.91–6.90 (m, 3H, ArH), 6.57 (d, = 8.4 Hz, 1H, ArH), 5.82 (d, = 1.8 Hz, 1H, CH), 5.09 (s, 1H, CH), 4.32 (br s, 1H, CH), 4.06 (s, 1H, CH), 4.00 (s, 3H, OCH, 3.80 (s, 3H, OCH, 3.55–3.54 (m, 1H, CH), 3.48–3.47 (m, 1H, CH), 3.35 (br s, 5H, CH, OCH, 2.62 (s, 1H, CH), 1.03 (br s, 3H, CH), 0.82 (brs, 1H, CH), 0.73–0.72 (m, 6H, CHC NMR (150 MHz, CDCl: 195.0, 174.7, 174.6, 173.6, 166.0, 165.1, 163.4, 158.5 (d, = 239.9 Hz), 146.6, 141.7, 138.8, 134.7, 130.4, 129.8, 129.4, 127.4, 126.2 (d, = 8.6 Hz), 123.0, 118.8 (d, = 25.8 Hz), 115.1 (d, = 23.1 Hz), 113.4, 108.4 (d, = 8.4 Hz), 96.6, 61.2, 55.4, 53.5, 51.9, 51.2, 50.5, 47.6, 46.0, 42.6, 40.2, 39.3, 29.0, 20.1, 19.7, 13.6; IR (KBr) : 3458, 2957, 1781, 1714, 1677, 1598, 1491, 1455, 1384, 1325, 1240, 1280, 1130, 1093, 1020, 960, 908, 868, 835, 807 cm; MS (/: HRMS (ESI) Calcd. for CHClFNO ([M+H]: 796.2432. Found: 796.2432. White solid, 86 %, m.p. 230–233 C; H NMR (600 MHz, DMSO-: 7.53–7.49 (m, 4H, ArH), 7.09–7.06 (m, 1H, ArH), 7.04 (d, = 8.4 Hz, 2H, ArH), 6.92–6.90 (m, 3H, ArH), 6.60 (d, = 8.4 Hz, 1H, ArH), 5.13 (s, 1H, CH), 4.63 (d, = 4.2 Hz, 1H, CH), 4.05 (br s, 1H, CH), 4.02 (s, 3H, OCH, 3.99 (s, 1H, CH), 3.80 (s, 3H, OCH, 3.58–3.56 (m, 1H, CH), 3.48–3.43 (m, 1H, CH), 3.40–3.39 (m, 1H, CH), 3.36 (s, 3H, OCH, 3.32 (br s, 1H, CH), 2.75 (s, 1H, CH), 1.46 (s, 3H, CH, 1.03–1.01 (m, 1H, CH), 0.93–0.91 (m, 2H, CH), 0.80–0.79 (m, 1H, CH), 0.67 (d, = 7.2 Hz, 3H, CHC NMR (150 MHz, CDCl: 195.2, 175.1, 174.4, 173.4, 166.1, 165.2, 163.5, 158.3 (d, = 240.2 Hz), 146.6, 139.6, 138.0, 134.7, 130.6, 130.2, 129.8, 129.4, 127.3, 127.2 (d, = 8.9 Hz), 122.3, 117.4 (d, = 25.5 Hz), 115.0 (d, = 23.4 Hz), 113.4, 108.4 (d, = 8.0 Hz), 97.0, 61.8, 55.7, 55.4, 53.5, 51.3, 50.4, 46.6, 45.0, 42.7, 40.2, 34.6, 29.0, 20.0, 19.5, 13.6; IR (KBr) : 3457, 2958, 1747, 1712, 1601, 1492, 1446, 1426, 1384, 1355, 1318, 1264, 1236, 1175, 1138, 1022, 956, 918, 896, 876, 825, 803 cm; MS (/: HRMS (ESI) Calcd. for CHClFNO ([M+H]: 796.2432. Found: 796.2429. White solid, 90 %, m.p. 300 C; H NMR (600 MHz, DMSO-: 7.43 (d, = 4.8 Hz, 2H, ArH), 7.27 (d, = 7.2 Hz, 1H, ArH), 6.90 (br s, 3H, ArH), 6.84 (br s, 1H, ArH), 5.50 (s, 1H, CH), 4.89 (d, = 3.0 Hz, 1H, CH), 4.47 (brs, 1H, CH), 4.00 (s, 3H, OCH, 3.98 (s, 1H, CH), 3.79 (s, 3H, OCH, 3.77–3.75 (m, 1H, CH), 3.69 (br s, 1H, CH), 3.36 (br s, 4H, CH, OCH, 3.26–3.24 (m, 1H, CH), 2.74 (s, 3H, OCH, 2.54 (s, 1H, CH), 1.00 (br s, 3H, CH), 0.82–0.78 (m, 1H, CH), 0.70 (br s, 3H, CH IR (KBr) : 3453, 2957, 1861, 1779, 1699, 1675, 1641, 1584, 1511, 1483, 1455, 1433, 1368, 1342, 1321, 1269, 1232, 1203, 1170, 1129, 1086, 1049, 1017, 972, 942, 924, 879, 841, 811 cm; MS (/: HRMS (ESI) Calcd. for CHClNNaO ([M+Na]: 741.1822. Found: 741.1808. White solid, 88 %, m.p. 283–285 C; H NMR (600 MHz, DMSO-: 7.30 (d, = 8.4 Hz, 2H, ArH), 7.17 (d, = 7.8 Hz, 2H, ArH), 7.08 (td, = 9.3 Hz, = 2.4 Hz, 1H, ArH), 6.88 (dd, = 8.4 Hz, = 4.2 Hz, 1H, ArH), 6.61 (dd, = 9.3 Hz, = 2.4 Hz, 1H, ArH), 5.06 (s, 1H, CH), 4.92 (dd, = 6.6 Hz, = 2.4 Hz, 1H, CH), 4.48 (dd, = 6.6 Hz, = 3.6 Hz, 1H, CH), 4.00–3.99 (m, 4H, CH, OCH, 3.76 (dd, = 7.5 Hz, = 3.6 Hz, 1H, CH), 3.67 (dd, = 7.5 Hz, = 3.6 Hz, 1H, CH), 3.36 (s, 3H, OCH, 3.28–3.27 (m, 1H, CH), 3.20–3.19 (m, 1H, CH), 2.71 (s, 3H, OCH, 2.56 (s, 1H, CH), 2.31 (s, 3H, CH, 1.02 (br s, 3H, CH), 0.81–0.79 (m, 1H, CH), 0.71 (d, = 7.2 Hz, 3H, CHC NMR (150 MHz, DMSO-: 194.8, 175.3, 174.2, 174.1, 165.4, 164.6, 163.1, 157.5 (d, = 236.1 Hz), 146.5, 140.6, 139.0, 138.2, 130.0, 129.8, 129.4, 129.1, 126.3, 125.9 (d, = 8.3 Hz), 122.7, 117.3 (d, = 22.5 Hz), 114.7 (d, = 23.3 Hz), 113.4, 109.3, 94.5, 60.2, 55.4, 53.3, 51.8, 50.8, 49.7, 47.0, 45.8, 42.1, 28.7, 20.6, 19.4, 19.2, 13.4; IR (KBr) : 3456, 2956, 1864, 1780, 1740, 1697, 1641, 1585, 1489, 1455, 1435, 1382, 1339, 1320, 1267, 1232, 1202, 1177, 1120, 1086, 1046, 1017, 979, 929, 872, 816, 792 cm; MS (/: HRMS (ESI) Calcd. for CHFNNaO ([M+Na]: 709.2168. Found: 709.2158.

Supporting information

H and C NMR spectra and 2D NMR for all new compounds are available. Crystallographic data 1c (CCDC 916455), 1h (CCDC 916456), 1m (CCDC 916457), 2b (CCDC 916458), 3e (CCDC 928874), 3i (CCDC 928875), 4d (CCDC 928873) have been deposited at the Cambridge Crystallographic Database Centre and are available on request (http://www.ccdc.cam.ac.uk). Below is the link to the electronic supplementary material. Supplementary material 1 (doc 4383 KB)
  18 in total

1.  An organocatalytic Michael-aldol cascade: formal [3+2] annulation to construct enantioenriched spirocyclic oxindole derivatives.

Authors:  Shu-Wen Duan; Yang Li; Yi-Yin Liu; You-Quan Zou; De-Qing Shi; Wen-Jing Xiao
Journal:  Chem Commun (Camb)       Date:  2012-03-21       Impact factor: 6.222

2.  Catalytic asymmetric exo'-selective [3+2] cycloaddition for constructing stereochemically diversified spiro[pyrrolidin-3,3'-oxindole]s.

Authors:  Atsuko Awata; Takayoshi Arai
Journal:  Chemistry       Date:  2012-06-11       Impact factor: 5.236

3.  A novel chiral oxazolidine organocatalyst for the synthesis of an oseltamivir intermediate using a highly enantioselective Diels-Alder reaction of 1,2-dihydropyridine.

Authors:  Hiroto Nakano; Kenichi Osone; Mitsuhiro Takeshita; Eunsang Kwon; Chigusa Seki; Haruo Matsuyama; Nobuhiro Takano; Yoshihito Kohari
Journal:  Chem Commun (Camb)       Date:  2010-05-26       Impact factor: 6.222

4.  Facile synthesis of dispirooxindole-fused heterocycles via domino 1,4-dipolar addition and Diels-Alder reaction of in situ generated Huisgen 1,4-dipoles.

Authors:  Jing Sun; Yan Sun; Hui Gong; Ya-Jing Xie; Chao-Guo Yan
Journal:  Org Lett       Date:  2012-10-10       Impact factor: 6.005

5.  [4 + 2] Cyclocondensation reactions of tungsten-dihydropyridine complexes and the generation of tri- and tetrasubstituted piperidines.

Authors:  Daniel P Harrison; Diana A Iovan; William H Myers; Michal Sabat; Sisi Wang; Victor E Zottig; W Dean Harman
Journal:  J Am Chem Soc       Date:  2011-10-26       Impact factor: 15.419

6.  Acylideneoxoindoles: a new class of reversible inhibitors of human transglutaminase 2.

Authors:  Cornelius Klöck; Xi Jin; Kihang Choi; Chaitan Khosla; Peter B Madrid; Andrew Spencer; Brian C Raimundo; Paul Boardman; Guido Lanza; John H Griffin
Journal:  Bioorg Med Chem Lett       Date:  2010-12-16       Impact factor: 2.823

7.  Dinuclear zinc catalyzed asymmetric spirannulation reaction: an umpolung strategy for formation of α-alkylated-α-hydroxyoxindoles.

Authors:  Barry M Trost; Keiichi Hirano
Journal:  Org Lett       Date:  2012-04-30       Impact factor: 6.005

8.  Total synthesis of (+)-lepadin B: stereoselective synthesis of nonracemic polysubstituted hydroquinolines using an RC-ROM process.

Authors:  Guillaume Barbe; André B Charette
Journal:  J Am Chem Soc       Date:  2008-09-27       Impact factor: 15.419

9.  Strategies for heterocyclic construction via novel multicomponent reactions based on isocyanides and nucleophilic carbenes.

Authors:  Vijay Nair; C Rajesh; A U Vinod; S Bindu; A R Sreekanth; J S Mathen; Lakshmi Balagopal
Journal:  Acc Chem Res       Date:  2003-12       Impact factor: 22.384

Review 10.  Strategies for the enantioselective synthesis of spirooxindoles.

Authors:  Nicolas R Ball-Jones; Joseph J Badillo; Annaliese K Franz
Journal:  Org Biomol Chem       Date:  2012-05-14       Impact factor: 3.876
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