Base catalysed domino and self-domino Michael–Aldol reactions: one-pot synthesis of dispirocyclopentaneoxindoles containing multiple chiral stereocenters

Abstract

A one-pot method for the construction of three classes of densely functionalized dispirocyclopentaneoxindoles containing multiple chiral stereocenters is developed. Base promoted self-domino and domino reactions with and without the participation of solvent, alcohol, is accomplished. Piperidine catalyzed self-domino reaction involves the participation of the nucleophilic solvent, alcohol, resulting in complex dispiro compounds containing four and five diastereoisomeric centers. Triethylamine promotes the self-domino reaction between two molecules of 3-phenacylideneoxindoles with added nucleophiles, and not with the solvent nucleophile. Diisopropylethylamine facilitates the domino reaction between 3-phenacylidineoxindole and phenacylacenaphthylenone allowing the construction of novel dispirocyclopentaneoxindoles with high yields and diastereoselectivity. A plausible mechanism is tentatively proposed to account for the diastereoselectivity of the domino Michael–Aldol reaction.

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The development of simple and efficient methods for the construction of synthetically and biologically important spirocyclic oxindoles has gained considerable importance.¹ We report, herein, the efficient one-pot synthesis of densely functionalized spirocyclopentaneoxindoles containing five-carbon and four-carbon chiral stereocenters including two non-contiguous dispiro stereocenters. Spirooxindole structural motif is commonly present in a number of natural and unnatural biologically active alkaloids.^2–4 The 3,3′-spirooxindoles are the most privileged structural motifs playing a vital role in biological activities,⁵ even though the biological importance of five or six membered spirocyclicoxindoles are not uncommon. Considering the biological significance of spirocyclopentaneoxindoles embodied in natural alkaloid derivatives⁶ such as marcfortine A, cirinalins A, citrinadin B, and cyclopiamine B (Fig. 1), efficient synthesis of these structural motifs containing multiple chiral stereocenters is both important and challenging to synthetic chemists.

Fig. 1 Natural products containing spirocyclopentaneoxindole scaffold.

In recent years, organocatalytic phosphine-catalyzed reactions have been explored for the synthesis of spirocyclopentaneoxindoles.^7,8 However, there are only a few reports available in literature for the efficient synthesis of spirocyclopentaneoxindoles,⁹ and very few methods are available for the construction of bispirooxindoles containing all carbon chiral stereocenters with multiple quaternary dispiro stereocenters. Recently, Barbas III et al. have reported an organocatalytic asymmetric synthesis of dispirocyclopentaneoxindoles.^3f Yan et al. have reported a base catalyzed diastereoselective domino synthesis of dispirocyclooxindoles.¹⁰ Several metal or organocatalyzed enantioselective syntheses of spirocyclopentaneoxindoles have also been successfully explored.^4c,7a,c,8,11 The recent report on the facile construction of novel bisspirocyclopentanebisoxindoles by self-domino reaction between two molecules of 3-phenacylideneoxindoles is particularly encouraging.¹² Literature survey shows that 3-phenacylideneoxindoles have long been used as active electron-deficient alkenes in many synthetic procedures such as 1,3-dipolar cycloaddition, Diels–Alder reaction, Michael addition, and versatile multicomponent reactions for the design of fused cyclic and spirocyclic frameworks.^13–15 However, there are only very few examples of the synthesis of dispirocyclopentanebisoxindoles involving 3-phenacylidineoxindoles. As a part of our interest in the development of methodologies for single-step construction of densely functionalized dispirooxindoles containing multiple chiral stereocenters,¹⁶ herein, we report organocatalytic domino Michael addition–Aldol reaction involving 3-phenacylideneoxindoles for the synthesis of three classes of spirocyclic oxindole derivatives.

Results and discussion

Encouraged by the self-domino reaction reported¹² by Yan et al., and our interest in one-pot multicomponent reactions,¹⁶ we set out to explore base-catalysed Michael–Aldol reaction (Scheme 1). When ethanol was used as the reaction medium and 5 mol% piperidine (pK_a 11.22) as base-catalyst, both the alcohol (solvent) and 2-aminopyridine acted as nucleophiles, leading to the formation of spirooxindoles 3a and 4a (Table 1). The ethoxy group in the dispirocyclopentanebisoxindole 4a apparently stems from the nucleophilic substitution of the solvent, ethanol. Although two products were formed, isolation of 3a and 4a could be easily achieved owing to the difference in their R_f values. The generality of this reaction to yield two classes of spirooxindoles was established by synthesizing a series of dispirooxindoles of the types 3 and 4 (Table 1). All the compounds were characterized using IR, NMR and mass analytical methods, and found to be a single diastereoisomer.

Scheme 1 Synthetic cascade approach to spirocyclicoxindoles.

Table 1 Substrate scope^a

Entry	R^1	R^2	R^3	R^4	R′′–OH	3/4	Yield^b (%)
a All reactions were carried out with 1.0 mmol 3-phenacylidineoxindole 1, 0.5 mmol aminopyridines 2, and 5 mol% piperidine in 10 mL alcohol.b Isolated yield.
1	Bn	H	Ph	H	EtOH	3a/4a	48/45
2	Bn	Cl	4-MeC6H4	H	EtOH	3b/4b	43/47
3	Bn	H	Ph	H	EtOH	3c/4c	45/46
4	Bn	F	Ph	H	MeOH	3d/4d	47/42

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Although the piperidine-catalyzed Michael–Aldol reaction gave the desired products 3 and 4 (Table 1) with excellent diastereoselectivity, the overall yield was poor with respect to 3 or 4. We envisioned that only 2-aminopyridine substituted products 3 would be formed in excellent yield if a weaker base, instead of piperidine, is used for catalysis. Thus, when 5 mol% triethylamine (pK_a 10.7) was used as the catalyst in ethanol medium neither 3a nor 4a was formed at room temperature. However, when the reaction mixture was heated under reflux for 30 min, only the 2-aminopyridine substituted spirooxindole 3a′ formed in 42% yield (Table 2), and the ethanol substituted product 4a′ could not be detected. Thus, triethylamine, being a weaker base than piperidine, doesn't seem to promote the participation of alcohol (a weaker nucleophile than 2-aminopyridine) in this self-domino reaction. The reaction was optimized with respect to the reaction temperature, time, solvent and amount of base needed for catalysis, so as to improve the yield of spirooxindole 3a′ (Table 2). The best result was obtained by refluxing the ethanolic solution of 1.0 mmol of (E)-1-benzyl-3-(2-oxo-2-phenyl ethylidene) indolin-2-one and 0.5 mmol of 2-aminopyridine in the presence of 5 mol% triethylamine for 4 h, that resulted in the formation of the desired spirooxindole 3a′ in 95% yield. Interestingly, the structurally related tertiary amine DABCO also yielded the spirooxindole 3a′ albeit at a relatively lower yield. Further, nucleophilic substitution of solvent was not observed when methanol was used as the reaction medium. Single crystal XRD data of spirocyclicoxindole 3a′ revealed the stereochemical disposition of various moieties in the newly formed five-member ring (Fig. 2). Notably, the stereochemical preferences adopted by 3a′ (Fig. 2) are similar to those of the spirooxindole derivatives synthesized using chiral^3f and achiral¹² organocatalysts. This observation reveals the strong influence of the transition state on the stereochemical outcome of the spirooxindole derivatives.

Table 2 Optimisation of reaction conditions^a

Entry	Base	Solvent	Temp (°C)	Time (hr)	Yield^b (%)
a Reaction conditions: 3-phenacylidineoxindole (1.0 mmol), 2-aminopyridine (0.5 mmol) and base catalyst (5 mol%) in different solvents (10 mL).b Isolated yield.
1	DABCO	EtOH	rt	8.0	—
2	DABCO	EtOH	70	7.2	25
3	Et3N	EtOH	rt	5.0	—
4	Et3N	EtOH	80	0.5	42
5	Et3N	EtOH	80	4.0	95
6	Et3N	MeOH	80	5.0	80
7	Et3N	CAN	80	6.0	—
8	Et3N	THF	80	6.2	—

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Fig. 2 Ortep-diagram of compound 3a′.

To investigate the generality of this reaction under the optimized conditions, we used various nucleophiles and substituted phenacylidineindolinones (Table 3). Though the reaction was carried out in alcoholic solution containing a non-chiral catalyst, the reaction proceeded smoothly and resulted in the diastereoselective formation of densely functionalized bispirooxindoles as a single isomer containing an all chiral cyclopentyl ring with two non-contiguous dispiro quaternary chiral stereocenters. In almost all the cases the products were obtained in good yields (Table 3). When 2-aminobenzthiazole (Table 3, entry 14) was used as the nucleophile, the reaction took a slightly longer time, and resulted in a lower yield, which may be ascribed to the bulkiness of the 2-aminobenzthiazole moiety. ¹H and ¹³C NMR spectra of the prepared bispirooxindoles clearly showed the existence of a single diastereoisomer in all the preparations, and the other possible diastereoisomer was not observed. The spectroscopic and X-ray diffraction analyses revealed that the isolated diastereoisomer contained two oxindole moieties in 1,3-trans orientation, while the 2-benzoyl group and the 5-aryl group were in cis orientation with respect to the newly formed five membered ring. As the oxindole moiety and the benzoyl group exist in the trans position in the starting 3-phenacylideneindolinone, only a multistep reaction process must have resulted in the observed thermodynamically most stable diastereoisomer in this domino reaction. Thus, the reaction proceeds following probably a similar mechanistic pathway as suggested by Yan et al.¹²

Table 3 Substrate scope^a

Entry	R^1	R^2	R^3	R^4/X	3	Yield^b (%)
a All reactions were carried out with 1.0 mmol 3-phenacylidineoxindole 1, 0.5 mmol aminopyridines 2, and 5 mol% Et3N in 10 mL ethanol.b Isolated yield.
1	Bn	F	Ph	H/CH	3a′	95
2	Bn	Cl	Ph	H/CH	3b′	89
3	Bn	Br	Ph	H/CH	3c′	87
4	Bn	H	4-BrC6H4	H/CH	3d′	82
5	Bn	H	4-Biphenyl	H/CH	3e′	78
6	Me	H	Ph	H/CH	3f′	87
7	Me	H	4-ClC6H4	H/CH	3g′	83
8	Bn	F	Ph	6-Me/CH	3h′	84
9	Bn	F	Ph	5-Br/CH	3i′	86
10	Bn	F	Ph	4-Me/CH	3j′	91
11	Bn	F	Ph	5-Cl/CH	3k′	88
12	Bn	F	Ph	H/N	3l′	93
13	Bn	H	4-OMeC6H4	H/N	3m′	90
14	Bn	H	Ph	2-Aminobenzthiazole	3n′	80

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Base catalyzed Michael addition of in situ generated 3-phenacylindolinone with 3-phenacylideneoxindole and subsequent intramolecular aldol condensation has yielded dispirocyclopentanebisoxindoles.^3f,10 Variously substituted dispirocyclopentanebisoxindoles has also been achieved through organocatalytic domino reaction between 3-substituted oxindole and 3-phenacylideneindolinone.¹² To probe base promoted synthesis of dispirocyclopentanebisoxindoles having only four chiral stereocenters and shed more light on domino Michael–Aldol reactions, we used DIPEA, a tertiary amine stronger than TEA, in the anticipated domino reaction involving 3-phenacylideneoxindole and phenacylacenaphthylenone. To our delight, the reaction in alcohol medium completed in about 4 h, yielding only a single diastereoisomer of the dispiro compound 5a. Further experiments were carried out to explore the generality of this domino reaction and the results are summarized in Table 4. The dispiro compounds 5a–t resulted from the domino reaction were thoroughly characterized using ¹H and ¹³C NMR, HRMS, and IR spectral data. Single-crystal X-ray diffraction data of 5f (Fig. 3) was used to confirm the structures of the diastereoisomers isolated from the domino reaction. Single-crystal structure of 5f and ¹H NMR spectra of 5a–t suggested that the dispiro compounds 5a–t existed as a single diastereoisomer. A comparison of single-crystal X-ray diffraction data of 5f and 3a′ revealed that the two aromatic moieties at the 1,3-positions are in trans orientation, while the 2-benzoyl group and the 5-aryl group are in cis orientation.¹⁷ Thus, both the self-domino reaction (Table 3) and the domino reaction (Table 4) seem to be highly diastereoselective reactions. There is one methylene unit in the newly formed cyclopentane moiety of 5a–t. Similar observations have been reported from organocatalytic domino reaction^3f and self-domino reactions.¹² These observations were useful for us to understand the reaction mechanism of the present study. Accordingly, a possible mechanism for this DIPEA promoted domino Michael–Aldol reaction is provided in Scheme 2.

Fig. 3 Ortep-diagram of compound 5f.

Table 4 Substrate scope^a

Entry	R^1	R^2	R^3	R^4	5	Yield^b (%)
a All reactions were carried out with 0.5 mmol 1, 0.5 mmol phenacylacenapthylenone, and 5 mol% DIPEA in 10 mL ethanol.b Isolated yield.
1	Bn	H	Ph	Ph	5a	92
2	Bn	H	4-MeC6H4	Ph	5b	83
3	Bn	H	4-OMeC6H4	Ph	5c	86
4	Bn	H	Ph	Ph	5d	72
5	Bn	F	Ph	Ph	5e	76
6	Bn	Cl	Ph	Ph	5f	74
7	Bn	Cl	4-MeC6H4	Ph	5g	80
8	Me	H	Ph	Ph	5h	71
9	3-Me–Bn	H	Ph	Ph	5i	65
10	H	H	Ph	Br	5j	70
11	Bn	H	Ph	Br	5k	76
12	3-Me–Bn	H	Ph	Br	5l	81
13	Bn	H	4-OMeC6H4	Br	5m	68
14	C3H3	H	Ph	Br	5n	78
15	Bn	H	OMe	Ph	5o	86
16	Bn	H	OEt	Ph	5p	83
17	C3H3	H	OMe	Ph	5q	74
18	C3H3	H	OEt	Ph	5r	72
19	C3H3	H	OEt	Br	5s	68
20	Bn	H	OEt	Br	5t	76

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Scheme 2 Plausible mechanism.

Conclusions

In summary, we have reported base promoted domino and self-domino reactions for the efficient synthesis of densely functionalized dispirocyclopentane oxindole derivatives. The unique advantages are: (1) piperidine catalyzed one-pot synthesis of densely functionalized dispirocyclopentanebisoxindoles using amine and alcohol nucleophiles, (2) triethylamine promoted selective synthesis of all five carbon chiral dispirocyclopentanebisoxindoles without interference from alcohol nucleophiles, and (3) diisopropylethylamine mediated domino synthesis of dispirocyclopentane derivatives containing only four chiral stereocenters including two non-contiguous quaternary dispiro chiral stereocenetrs. The reactions of 3-phenacylideneoxindoles with substituted 1a–r also proceeded smoothly to give the expected dispirocylopentane compounds in moderate yields. Use of readily available starting materials, simple reaction conditions, operational simplicity (non-requirement of chromatographic separation) are the other advantages.

Experimental section

General methods

All the reagents were purchased from Sigma-Aldrich and used without further purification. Pre-coated plates (Merck, silica gel 60 GF₂₅₄, 0.25 mm) were used for TLC analysis. The ¹H NMR and ¹³C NMR spectra were recorded on Bruker Avance 400 MHz Spectrometer. The ¹³C NMR, DEPT experiments were carried out on Bruker Avance 100 MHz Spectrometer. The chemical shifts (δ) for ¹H and ¹³C are given in ppm with reference to TMS (zero ppm). Coupling constants are given in Hertz.

General procedure for the preparation of compounds 3a–d and 4a–d

Procedure 1. In an oven dried 50 mL round-bottom flask 2 mmol 3-phenacylidineoxindole, 1 mmol substituted 2-aminopyridine, 10 mL ethanol and 5 mol% piperidine were taken and the contents of the flask were heated under reflux ∼80 °C until the starting materials were consumed. The reaction mixture was allowed to cool to room temperature and then diluted with ethylacetate and water. The organic layer was separated, dried using anhydrous Na₂SO₄ and the solvent was removed under reduced pressure. The crude products obtained were purified using column chromatography (silica gel 60–120 mesh).

(2′S,3R,3′R,4′R,5′S)-2′-Benzoyl-1,1′′-dibenzyl-4′-hydroxy-4′-phenyl-5′-[(pyridin-2-yl)amino]-1,1′′,2,2′′-tetrahydrodispiro[indole-3,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (3a). White solid, Mp: 260–262 °C; IR (KBr): 3368, 3208, 3070, 2923, 2851, 1719, 1601, 1483, 1352, 1179, 1074, 1008, 976, 815, 773, 733, 691, 540, 455, 409 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.28 (s, 1H), 7.91 (s, 1H), 7.77 (s, 1H), 7.25–7.06 (m, 16H), 6.96 (t, J = 7.6 Hz, 4H), 6.89 (d, J = 6.0 Hz, 2H), 6.53 (d, J = 6.8 Hz, 2H), 6.42 (t, J = 5.6 Hz, 1H), 6.37 (d, J = 8.4 Hz, 1H), 6.05 (d, J = 7.6 Hz, 2H), 5.30 (d, J = 16.0 Hz, 2H), 5.17 (s, 1H), 5.13 (d, J = 15.6 Hz, 1H), 4.44 (d, J = 16.0 Hz, 1H), 4.27 (d, J = 15.6 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 194.6, 180.3, 176.0, 156.2, 147.9, 142.5, 140.4, 137.3, 135.5, 134.9, 134.8, 133.6, 131.3, 131.1, 131.0, 129.7, 129.2, 129.0, 128.8, 128.6, 128.5, 128.4, 127.9, 127.8, 127.7, 127.5, 127.3, 127.1, 127.0, 126.3, 125.8, 122.6, 113.8, 110.1, 109.7, 107.3, 85.7, 64.0, 62.6, 62.5, 59.6, 44.6, 44.2; HRMS (EI) calcd for [C₅₁H₄₀N₄O₄]⁺: 772.3050; found: 772.3048.

(2′S,3R,3′R,4′R,5′S)-2′-Benzoyl-1,1′′-dibenzyl-5′-ethoxy-4′-hydroxy-4′-phenyl-1,1′′,2,2′′-tetrahydrodispiro[indole-3,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (4a). White solid, Mp: 260–262 °C; IR (KBr): 3362, 3201, 3060, 2920, 2789, 1720, 1615, 1475, 1350, 1180, 1065, 982, 975, 819, 775, 690, 545, 450, 408 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.19 (s, 1H), 7.95 (s, 1H), 7.36–7.33 (m, 6H), 7.29–7.22 (m, 6H), 7.19–7.09 (m, 5H), 7.07–6.99 (m, 5H), 6.59 (d, J = 6.8 Hz, 2H), 6.52 (s, 1H), 6.34 (d, J = 8.4 Hz, 1H), 6.30 (d, J = 8.4 Hz, 1H), 6.06 (s, 1H), 5.27–5.21 (m, 3H), 4.47 (d, J = 16.4 Hz, 1H), 4.27 (d, J = 15.2 Hz, 1H), 3.28–3.21 (m, 1H), 3.10–3.02 (m, 3H), 0.79 (t, J = 7.2 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 195.0, 179.2, 176.4, 142.2, 140.7, 136.2, 135.5, 134.8, 134.3, 131.6, 131.2, 130.8, 129.5, 129.0, 128.7, 128.6, 128.5, 128.3, 128.0, 127.7, 127.6, 127.5, 127.3, 126.7, 126.3, 122.3, 109.9, 109.4, 88.1, 83.9, 68.5, 64.7, 62.7, 58.8, 44.8, 44.1, 15.2; HRMS (EI) calcd for [C₄₈H₄₀N₂O₅]⁺: 724.2937; found: 724.2936.

(2′S,3R,3′R,4′R,5′S)-1,1′′-Dibenzyl-5,5′′-dichloro-4′-hydroxy-2′-(4-methylbenzoyl)-4′-(4-methylphenyl)-5′-[(pyridin-2-yl)amino]-1,1′′,2,2′′-tetrahydrodispiro[indole-3,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (3b). White solid, Mp: 276–278 °C; IR (KBr): 3380, 3364, 3066, 2928, 2842, 1716, 1604, 1489, 1458, 1337, 1276, 1176, 1031, 984, 890, 802, 775, 732, 695, 617, 532, 450 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.31 (s, 1H), 7.93 (s, 1H), 7.77 (d, J = 4.0 Hz, 1H), 7.16–7.09 (m, 12H), 6.97 (d, J = 7.6 Hz, 2H), 6.90–6.82 (m, 8H), 6.49 (d, J = 7.2 Hz, 2H), 6.39 (t, J = 6.0 Hz, 1H), 6.32 (d, J = 8.0 Hz, 1H), 6.04 (d, J = 8.4 Hz, 1H), 5.93 (d, J = 8.4 Hz, 1H), 5.32 (d, J = 16.4 Hz, 1H), 5.21 (d, J = 16.8 Hz, 1H), 4.41 (d, J = 16.0 Hz, 1H), 4.16 (d, J = 15.6 Hz, 1H), 2.28 (s, 3H), 2.23 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 195.1, 181.0, 176.4, 143.4, 142.6, 140.5, 137.6, 137.1, 135.2, 134.2, 133.8, 133.0, 131.6, 129.5, 128.8, 128.6, 128.4, 128.0, 127.6, 127.3, 127.2, 127.1, 127.0, 126.8, 126.6, 126.4, 125.8, 113.5, 109.8, 109.5, 107.1, 86.0, 64.3, 62.5, 59.9, 44.5, 44.1, 21.5, 21.2; HRMS (EI) calcd for [C₅₃H₄₂Cl₂N₄O₄]⁺: 868.2583; found: 868.2582.

(2′S,3R,3′R,4′R,5′S)-1,1′′-Dibenzyl-5,5′′-dichloro-5′-ethoxy-4′-hydroxy-2′-(4-methylbenzoyl)-4′-(4-methylphenyl)-1,1′′,2,2′′-tetrahydrodispiro[indole-3,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (4b). White solid, Mp: 284–286 °C; IR (KBr): 3299, 3072, 2922, 2852, 1705, 1682, 1609, 1482, 1428, 1343, 1177, 1096, 973, 811, 785, 734, 700, 577, 534, 457 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.23 (s, 1H), 7.97 (s, 1H), 7.32 (t, J = 7.2 Hz, 5H), 7.19–7.11 (m, 7H), 7.05 (d, J = 8.8 Hz, 1H), 6.98–6.93 (m, 3H), 6.86 (d, J = 7.6 Hz, 2H), 6.54 (d, J = 7.2 Hz, 2H), 6.48 (s, 1H), 6.23 (d, J = 8.4 Hz, 2H), 6.12 (s, 1H), 5.33 (d, J = 15.2 Hz, 1H), 5.26 (d, J = 16.4 Hz, 2H), 4.44 (d, J = 16.0 Hz, 1H), 4.16 (d, J = 15.6 Hz, 1H), 3.33–3.25 (m, 1H), 3.12–3.05 (m, 1H), 2.33 (s, 3H), 2.26 (s, 3H), 0.79 (t, J = 7.2 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 195.6, 179.5, 176.8, 143.3, 142.3, 140.8, 137.2, 135.1, 134.6, 134.3, 134.2, 132.1, 129.3, 128.8, 128.6, 128.5, 128.4, 128.0, 127.9, 127.4, 127.3, 127.0, 126.7, 126.5, 126.4, 109.6, 109.1, 88.2, 84.3, 68.3, 64.9, 62.6, 59.1, 44.7, 44.0, 29.7, 21.2, 15.2; HRMS (EI) calcd for [C₅₀H₄₂Cl₂N₂O₅]⁺: 820.2471; found: 820.2470.

(2′S,3R,3′R,4′R,5′S)-2′-Benzoyl-1,1′′-dibenzyl-5′-[(5-bromopyridin-2-yl)amino]-4′-hydroxy-4′-phenyl-1,1′′,2,2′′-tetrahydrodispiro[indole-3,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (3c). White solid, Mp: 278–280 °C; IR (KBr): 3419, 3311, 2924, 2849, 1705, 1616, 1580, 1491, 1396, 1354, 1223, 1180, 1098, 1072, 1016, 970, 918, 885, 803, 750, 727, 691, 577, 531, 508, 455, 400 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.28 (d, J = 7.6 Hz, 1H), 7.96 (d, J = 7.2 Hz, 1H), 7.77 (s, 1H), 7.30–7.15 (m, 6H), 7.13–7.05 (m, 15H), 6.93 (s, 1H), 6.87 (t, J = 8.0 Hz, 3H), 6.52 (d, J = 7.2 Hz, 2H), 6.41 (d, J = 7.6 Hz, 1H), 6.02 (d, J = 8.0 Hz, 1H), 5.87 (d, J = 8.8 Hz, 1H), 5.38 (d, J = 14.0 Hz, 2H), 5.26 (d, J = 15.6 Hz, 1H), 5.18 (d, J = 16.4 Hz, 1H), 4.48 (d, J = 16.0 Hz, 1H), 4.11 (d, J = 16.0 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 195.8, 181.2, 176.6, 155.4, 148.5, 143.8, 141.9, 139.3, 137.0, 136.0, 135.5, 134.1, 132.4, 129.5, 128.9, 128.8, 128.5, 128.3, 127.8, 127.6, 127.1, 126.7, 126.4, 125.5, 124.2, 122.1, 109.0, 108.8, 108.3, 107.5, 86.1, 64.0, 62.9, 62.5, 59.5, 44.3, 43.9; HRMS (EI) calcd for [C₅₁H₃₉BrN₄O₄]⁺: 850.2155; found: 815.2153.

(2′S,3R,3′R,4′R,5′S)-2′-Benzoyl-1,1′′-dibenzyl-5′-ethoxy-4′-hydroxy-4′-phenyl-1,1′′,2,2′′-tetrahydrodispiro[indole-3,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (4c). White solid, Mp: 260–262 °C; IR (KBr): 3362, 3201, 3060, 2920, 2789, 1720, 1615, 1475, 1350, 1180, 1065, 982, 975, 819, 775, 690, 545, 450, 408 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.19 (s, 1H), 7.95 (s, 1H), 7.36–7.33 (m, 6H), 7.29–7.22 (m, 6H), 7.19–7.09 (m, 5H), 7.07–6.99 (m, 5H), 6.59 (d, J = 6.8 Hz, 2H), 6.52 (s, 1H), 6.34 (d, J = 8.4 Hz, 1H), 6.30 (d, J = 8.4 Hz, 1H), 6.06 (s, 1H), 5.27–5.21 (m, 3H), 4.47 (d, J = 16.4 Hz, 1H), 4.27 (d, J = 15.2 Hz, 1H), 3.28–3.21 (m, 1H), 3.10–3.02 (m, 3H), 0.79 (t, J = 7.2 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 195.0, 179.2, 176.4, 142.2, 140.7, 136.2, 135.5, 134.8, 134.3, 131.6, 131.2, 130.8, 129.5, 129.0, 128.7, 128.6, 128.5, 128.3, 128.0, 127.7, 127.6, 127.5, 127.3, 126.7, 126.3, 122.3, 109.9, 109.4, 88.1, 83.9, 68.5, 64.7, 62.7, 58.8, 44.8, 44.1, 15.2; HRMS (EI) calcd for [C₄₈H₄₀N₂O₅]⁺: 724.2937; found: 724.2936.

(2′S,3R,3′R,4′R,5′S)-2′-Benzoyl-1,1′′-dibenzyl-5,5′′-difluoro-4′-hydroxy-4′-phenyl-5′-[(pyridin-2-yl)amino]-1,1′′,2,2′′-tetrahydrodispiro[indole-3,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (3d). White solid, Mp: 285–287 °C; IR (KBr): 3684, 3384, 3064, 2918, 2852, 1709, 1601, 1489, 1451, 1347, 1266, 1177, 1031, 981, 892, 804, 777, 742, 692, 607, 534, 453 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.18 (d, J = 8.4 Hz, 1H), 7.77–7.73 (m, 2H), 7.31–7.22 (m, 4H), 7.15–7.04 (m, 14H), 6.94 (s, 1H), 6.85 (d, J = 7.2 Hz, 3H), 6.55–6.49 (m, 3H), 6.39 (t, J = 6.0 Hz, 1H), 6.31 (dd, J = 4.0 Hz, 4.0 Hz, 1H), 6.05 (d, J = 8.4 Hz, 1H), 5.89 (dd, J = 4.0 Hz, 4.0 Hz, 1H), 5.28 (t, J = 7.2 Hz, 3H), 5.18 (d, J = 16.4 Hz, 1H), 4.46 (d, J = 16.0 Hz, 1H), 4.07 (d, J = 16.0 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 195.6, 181.1, 176.4, 161.2, 158.8, 157.6, 156.4, 147.9, 139.8, 137.9, 137.1, 136.9, 135.8, 135.2, 133.8, 132.6, 131.5, 128.8, 128.6, 128.2, 128.1, 128.0, 127.8, 127.6, 127.2, 127.0, 126.7, 126.6, 126.4, 115.3, 115.2, 115.1, 114.9, 114.6, 114.4, 113.7, 113.5, 109.5, 109.4, 109.3, 109.2, 107.2, 86.2, 64.4, 62.6, 60.0, 53.4, 44.4, 44.1; HRMS (EI) calcd for [C₅₁H₃₈F₂N₄O₄]⁺: 808.2861; found: 808.2560.

(2′S,3R,3′R,4′R,5′S)-2′-Benzoyl-1,1′′-dibenzyl-5,5′′-difluoro-4′-hydroxy-5′-methoxy-4′-phenyl-1,1′′,2,2′′-tetrahydrodispiro[indole-3,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (4d). White solid, Mp: 217–219 °C; IR (KBr): 3346, 3069, 2919, 2846, 2330, 1965, 1830, 1700, 1607, 1492, 1345, 1261, 1177, 1103, 980, 811, 692, 603, 550, 457 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.07 (d, J = 8.4 Hz, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.36–7.25 (m, 11H), 7.19–7.08 (m, 7H), 6.81 (d, J = 9.2 Hz, 1H), 6.77 (s, 1H), 6.65 (t, J = 8.4 Hz, 1H), 6.55 (d, J = 7.2 Hz, 2H), 6.26–6.20 (m, 2H), 6.10 (s, 1H), 5.45 (d, J = 15.2 Hz, 1H), 5.34 (s, 1H), 5.13 (d, J = 16.4 Hz, 1H), 4.48 (d, J = 16.0 Hz, 1H), 4.08 (d, J = 15.2 Hz, 1H), 3.04 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 195.9, 179.6, 176.8, 159.9, 158.7, 157.6, 139.6, 138.0, 136.8, 135.2, 134.7, 132.6, 132.1, 132.0, 128.9, 128.6, 128.1, 128.0, 127.8, 127.3, 127.0, 126.5, 126.3, 115.2, 115.0, 114.9, 114.8, 114.7, 114.4, 114.2, 113.9, 109.3, 109.2, 109.1, 109.0, 89.5, 84.6, 64.9, 62.5, 60.2, 58.9, 44.7, 44.0; HRMS (EI) calcd for [C₄₇H₃₇F₂N₂O₅]⁺: 747.2671; found: 747.2670.

General procedure for the preparation of compounds 3a′–n′

Procedure 2. With slight modification of procedure 1 and using 1 mmol 3-phenacylidineoxindole, 0.5 mmol substituted 2-aminopyridine, 10 mL ethanol and 5 mol% triethylamine only a single crude product was obtained. The crude product was separated by filtration, washed with 10–15 mL of ethanol to obtain pure white solid that did not require further purification.

(2′S,3R,3′R,4′R,5′S)-2′-Benzoyl-1,1′′-dibenzyl-5,5′′-difluoro-4′-hydroxy-4′-phenyl-5′-[(pyridin-2-yl)amino]-1,1′′,2,2′′-tetrahydrodispiro[indole-3,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (3a′). White solid, Mp: 238–240 °C; IR (KBr): 3383, 3316, 3063, 2922, 2856, 1712, 1602, 1493, 1450, 1384, 1356, 1270, 1177, 1075, 1032, 895, 845, 809, 774, 747, 692, 606, 564, 532 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.17 (d, J = 8.8 Hz, 1H), 7.77 (d, J = 8.0 Hz, 1H), 7.73 (d, J = 8.0 Hz, 1H), 7.32–7.23 (m, 5H), 7.18–7.04 (m, 13H), 6.95 (s, 1H), 6.85 (d, J = 7.6 Hz, 3H), 6.54 (t, J = 8.8 Hz, 1H), 6.49 (d, J = 7.2 Hz, 2H), 6.40 (t, J = 6.0 Hz, 1H), 6.31 (dd, J = 4.0 Hz, 4.0 Hz, 1H), 6.06 (d, J = 8.0 Hz, 1H), 5.88 (dd, J = 3.6 Hz, 3.6 Hz, 1H), 5.29 (t, J = 7.6 Hz, 3H), 5.20 (d, J = 16.0 Hz, 1H), 4.46 (d, J = 16.0 Hz, 1H), 4.07 (d, J = 15.6 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 195.7, 181.1, 176.4, 160.1 (d, J = 240.45 Hz), 158.7 (d, J = 238.21 Hz), 156.5, 148.1, 139.9, 137.9, 137.0, 136.9, 135.9, 135.2, 133.8, 132.6, 131.5, 128.8, 128.6, 128.1, 128.0, 127.9, 127.6, 127.2, 127.0, 126.7, 126.6, 126.4, 115.3 (d, J = 15.82 Hz), 115.0 (d, J = 18.83 Hz), 114.5 (d, J = 24.03 Hz), 113.6 (d, J = 21.76 Hz), 109.32 (d, J = 8.37 Hz), 109.4 (d, J = 8.03 Hz), 107.2, 86.2, 64.5, 62.7, 60.1, 58.4, 44.5, 44.1; HRMS (EI) calcd for [C₅₁H₃₈F₂N₄O₄]⁺: 808.2861; found: 808.2860.

(2′S,3R,3′R,4′R,5′S)-2′-Benzoyl-1,1′′-dibenzyl-5,5′′-dichloro-4′-hydroxy-4′-phenyl-5′-[(pyridin-2-yl)amino]-1,1′′,2,2′′-tetrahydrodispiro[indole-3,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (3b′). White solid, Mp: 243–245 °C; IR (KBr): 3387, 3258, 3070, 3031, 2938, 2856, 1958, 1708, 1692, 1657, 1598, 1481, 1434, 1376, 1333, 1302, 1239, 1165, 1075, 962, 899, 809, 755, 692, 630, 587, 552, 501, 532, 462 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.34 (s, 1H), 7.95 (s, 1H), 7.77 (d, J = 4.8 Hz, 1H), 7.29–7.23 (m, 5H), 7.19–7.04 (m, 14H), 6.90 (s, 1H), 6.85–6.80 (m, 3H), 6.45 (d, J = 7.2 Hz, 2H), 6.40 (t, J = 6.0 Hz, 1H), 6.32 (d, J = 8.4 Hz, 1H), 6.06 (d, J = 8.4 Hz, 1H), 5.88 (d, J = 8.0 Hz, 1H), 5.31–5.23 (m, 4H), 4.44 (d, J = 16.4 Hz, 1H), 4.7 (d, J = 16.0 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 195.8, 181.2, 176.3, 156.5, 148.2, 142.6, 140.6, 137.2, 137.1, 135.9, 135.2, 133.8, 132.7, 131.6, 129.7, 129.0, 128.9, 128.7, 128.4, 128.2, 128.1, 128.0, 127.8, 127.4, 127.3, 127.2, 126.8, 126.7, 126.4, 125.9, 113.7, 110.0, 109.7, 107.4, 86.3, 64.4, 62.9, 62.7, 59.9, 44.5, 44.2; HRMS (EI) calcd for [C₅₁H₃₈Cl₂N₄O₄]⁺: 840.2270; found: 840.2270.

(2′S,3R,3′R,4′R,5′S)-2′-Benzoyl-1,1′′-dibenzyl-5,5′′-dibromo-4′-hydroxy-4′-phenyl-5′-[(pyridin-2-yl)amino]-1,1′′,2,2′′-tetrahydrodispiro[indole-3,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (3c′). White solid, Mp: 249–251 °C; IR (KBr): 3387, 3254, 3066, 3031, 2930, 1708, 1692, 1653, 1606, 1477, 1426, 1376, 1337, 1239, 1173, 1079, 970, 806, 747, 696, 634, 583, 540, 466 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ (ppm) 8.46 (d, J = 1.8 Hz, 1H), 8.08 (d, J = 1.7 Hz, 1H), 7.77 (d, J = 3.9 Hz, 1H), 7.30–7.22 (m, 6H), 7.19–7.11 (m, 5H), 7.12–7.03 (m, 9H), 6.96 (dd, J = 8.3, 1.9 Hz, 1H), 6.88 (s, 1H), 6.85 (d, J = 7.5 Hz, 2H), 6.45 (d, J = 7.1 Hz, 2H), 6.42–6.37 (m, 1H), 6.27 (d, J = 8.3 Hz, 1H), 6.05 (d, J = 8.4 Hz, 1H), 5.83 (d, J = 8.3 Hz, 1H), 5.28 (t, J = 7.4 Hz, 2H), 5.24 (d, J = 15.2 Hz, 1H), 4.44 (d, J = 16.2 Hz, 1H), 4.07 (d, J = 15.8 Hz, 1H). ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 195.7, 180.9, 176.1, 156.3, 147.9, 143.0, 141.0, 137.1, 136.9, 135.8, 135.0, 133.6, 132.5, 131.8, 131.8, 131.0, 129.8, 129.7, 128.8, 128.6, 128.6, 128.5, 128.1, 127.9, 127.9, 127.6, 127.2, 127.0, 126.7, 126.6, 126.3, 118.8, 116.9, 114.7, 114.0, 113.6, 110.4, 110.1, 107.2, 86.1, 64.2, 62.8, 62.6, 59.7, 44.4, 44.0. HRMS (EI) calcd for [C₅₁H₃₈Br₂N₄O₄]⁺: 928.1260; found: 928.1258.

(1′R,2′S,3R,4′R,5′S)-1,1′′-Dibenzyl-2′-(4-bromobenzoyl)-4′-(4-bromophenyl)-4′-hydroxy-5′-[(pyridin-2-yl)amino]-1,1′′,2,2′′-tetrahydrodispiro[indole-3,3′-cyclopentane-1′,3′′-indole]-2,2′′-dione (3d′). White solid, Mp: 264–266 °C; IR (KBr): 3371, 3055, 1719, 1676, 1614, 1583, 1485, 1466, 1395, 1364, 1231, 1177, 1063, 1013, 817, 751, 743, 692, 673, 552, 517, 454 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.25 (d, J = 6.8 Hz, 1H), 7.93 (d, J = 6.4 Hz, 1H), 7.79 (s, 1H), 7.92–6.24 (m, 23H), 6.58 (d, J = 6.0 Hz, 2H), 6.46 (d, J = 6.8 Hz, 1H), 6.39 (s, 1H), 6.13 (d, J = 7.2 Hz, 1H), 5.95 (d, J = 7.6 Hz, 1H), 5.27 (d, J = 7.6 Hz, 2H), 5.14 (d, J = 14.8 Hz, 1H), 4.47 (d, J = 15.6 Hz, 1H), 4.23 (d, J = 15.6 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 194.9, 181.2, 178.5, 156.6, 148.0, 143.8, 141.9, 137.2, 135.6, 135.4, 135.3, 134.0, 131.1, 130.8, 129.3, 129.1, 128.9, 128.7, 128.5, 127.7, 127.4, 127.2, 127.0, 126.8, 126.4, 126.1, 125.5, 124.2, 122.3, 122.2, 113.6, 109.1, 108.8, 106.8, 85.8, 63.9, 63.0, 62.3, 59.5, 44.5, 44.1; HRMS (EI) calcd for [C₅₁H₃₈Br₂N₄O₄]⁺: 928.1260; found: 928.1260.

(1′R,2′S,3R,4′R,5′S)-1,1′′-Dibenzyl-4′-hydroxy-2′-(4-phenylbenzoyl)-4′-(4-phenylphenyl)-5′-[(pyridin-2-yl)amino]-1,1′′,2,2′′-tetrahydrodispiro[indole-3,3′-cyclopentane-1′,3′′-indole]-2,2′′-dione (3e′). White solid, Mp: 206–208 °C; IR (KBr): 3031, 1704, 1684, 1610, 1493, 1466, 1387, 1352, 1231, 1177, 1009, 845, 751, 692, 645, 552, 517 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.25 (d, J = 7.3 Hz, 1H), 8.02 (d, J = 6.2 Hz, 1H), 7.57 (d, J = 6.7 Hz, 2H), 7.48–7.33 (m, 11H), 7.26 (s, 10H), 7.20 (s, 3H), 7.13 (d, J = 7.6 Hz, 3H), 7.05 (s, 2H), 6.96 (s, 4H), 6.59 (d, J = 5.9 Hz, 2H), 6.43 (d, J = 6.8 Hz, 1H), 6.34 (d, J = 7.5 Hz, 1H), 5.42 (s, 1H), 5.26 (d, J = 16.7 Hz, 1H), 5.20 (d, J = 15.9 Hz, 1H), 4.56 (d, J = 14.4 Hz, 1H), 4.47 (d, J = 16.2 Hz, 1H), 4.36 (d, J = 14.8 Hz, 1H), 2.61 (d, J = 14.2 Hz, 1H). ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 195.9, 183.9, 176.9, 144.8, 143.8, 141.6, 140.5, 140.2, 139.5, 137.5, 135.7, 135.6, 134.8, 130.4, 128.9, 128.9, 128.7, 128.5, 128.4, 128.3, 128.1, 127.8, 127.6, 127.3, 127.1, 127.0, 126.8, 126.6, 126.3, 126.2, 125.8, 124.3, 121.9, 108.8, 108.5, 84.4, 66.6, 65.4, 54.3, 46.9, 44.6, 43.9. HRMS (EI) calcd for [C₆₃H₄₈N₄O₄]⁺: 924.3676; found: 924.3674.

(2′S,3R,3′R,4′R,5′S)-2′-Benzoyl-4′-hydroxy-1,1′′-dimethyl-4′-phenyl-5′-[(pyridin-2-yl)amino]-1,1′′,2,2′′-tetrahydrodispiro[indole-3,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (3f′). White solid, Mp: 228–230 °C; IR (KBr): 3375, 3285, 3070, 1715, 1684, 1602, 1489, 1430, 1376, 1329, 1286, 1235, 1181, 1149, 1067, 1009, 973, 927, 813, 770, 731, 657, 599, 536, 474 cm⁻¹; ¹H NMR (400 MHZ, CDCl₃): δ (ppm) 8.36 (d, J = 4.4 Hz, 1H), 7.87 (d, J = 7.2 Hz, 1H), 7.28–7.22 (m, 4H), 7.13–6.92 (m, 1H), 6.64 (d, J = 7.2 Hz, 2H), 6.35 (d, J = 7.2 Hz, 2H), 6.25 (d, J = 6.8 Hz, 1H), 6.13 (s, 1H), 5.57 (d, J = 10.8 Hz, 1H), 5.04 (s, 1H), 2.78 (s, 3H), 2.31 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 196.9, 176.7, 174.6, 157.0, 144.8, 138.5, 137.3, 136.8, 131.9, 131.5, 128.4, 128.3, 127.6, 127.5, 127.3, 126.9, 126.2, 125.9, 122.4, 120.8, 111.7, 107.3, 106.7, 102.9, 84.9, 65.0, 36.1, 62.2, 58.0, 25.5, 25.0; HRMS (EI) calcd for [C₃₉H₃₂N₄O₄]⁺: 620.2424; found: 620.2424.

(2′S,3R,3′R,4′R,5′S)-2′-(4-Chlorobenzoyl)-4′-(4-chlorophenyl)-4′-hydroxy-1,1′′-dimethyl-5′-[(pyridin-2-yl)amino]-1,1′′,2,2′′-tetrahydrodispiro[indole-3,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (3g′). White solid, Mp: 258–260 °C; IR (KBr): 3370, 3278, 3072, 1709, 1686, 1608, 1478, 1435, 1366, 1320, 1284, 1232, 1171, 1141, 1005, 968, 921, 813, 770, 735, 650, 595, 526, 472 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.23 (d, J = 6.8 Hz, 1H), 7.85 (d, J = 7.6 Hz, 1H), 7.71 (s, 1H), 7.66 (s, 1H), 7.32 (t, J = 7.2 Hz, 1H), 7.14 (t, J = 7.2 Hz, 1H), 7.12–6.98 (m, 9H), 6.92 (b, s, 5H), 6.70 (d, J = 7.6 Hz, 1H), 6.35 (d, J = 6.4 Hz, 1H), 6.27 (d, J = 18.4 Hz, 1H), 6.11 (d, J = 8.0 Hz, 1H), 5.44 (d, J = 10.0 Hz, 1H), 5.16 (s, 1H), 3.04 (s, 3H), 2.94 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 194.8, 180.3, 175.9, 156.8, 147.4, 144.1, 142.6, 138.4, 136.8, 1351, 134.8, 133.1, 129.2, 128.9, 128.4, 128.2, 127.9, 127.8, 126.9, 125.9, 125.3, 123.7, 121.8, 113.3, 107.7, 107.6, 107.3, 85.5, 64.0, 61.6, 61.2, 59.1, 26.6, 25.8; HRMS (EI) calcd for [C₃₉H₃₀Cl₂N₄O₄]⁺: 688.1644; found: 688.1643.

(2′S,3R,3′R,4′R,5′S)-2′-Benzoyl-1,1′′-dibenzyl-5,5′′-difluoro-4′-hydroxy-5′-[(6-methylpyridin-2-yl)amino]-4′-phenyl-1,1′′,2,2′′-tetrahydrodispiro[indole-3,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (3h′). White solid, Mp: 234–236 °C; IR (KBr): 3371, 3332, 1712, 1665, 1606, 1575, 1485, 1450, 1384, 1341, 1270, 1227, 1165, 1036, 973, 841, 806, 782, 739, 696, 610, 587, 536, 462 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.20 (d, J = 7.7 Hz, 1H), 7.74 (d, J = 7.1 Hz, 1H), 7.27 (d, J = 19.6 Hz, 5H), 7.06 (d, J = 22.7 Hz, 11H), 7.02 (d, J = 7.1 Hz, 2H), 6.86 (dd, J = 17.8, 8.8 Hz, 2H), 6.74 (d, J = 6.6 Hz, 2H), 6.56–6.43 (m, 3H), 6.31 (d, J = 4.6 Hz, 1H), 6.27 (d, J = 6.7 Hz, 1H), 5.91 (d, J = 7.7 Hz, 1H), 5.83 (d, J = 4.0 Hz, 1H), 5.37–5.15 (m, 4H), 4.46 (d, J = 16.2 Hz, 1H), 4.00 (d, J = 15.9 Hz, 1H), 1.96 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 195.7, 181.1, 176.3, 160.1 (d, J = 240.0 Hz), 158.7 (d, J = 238.1 Hz), 156.9, 155.8, 139.9, 137.9, 137.3, 136.9, 135.9, 135.2, 133.8, 132.5, 132.1, 132.1, 128.7, 128.6, 128.0, 127.9, 127.9, 127.4, 127.2, 126.9, 126.7, 126.3, 126.3, 115.2 (d, J = 24.0 Hz), 114.1 (d, J = 23.8 Hz), 113.6 (d, J = 25.1 Hz), 112.5, 109.3 (J = 7.9 Hz), 109.1 (d, J = 8.4 Hz), 104.2, 86.2, 64.4, 63.0, 62.7, 60.1, 44.4, 44.1, 23.8; HRMS (EI) calcd for [C₅₂H₄₀F₂N₄O₄]⁺: 822.3018; found: 822.3016.

(2′S,3R,3′R,4′R,5′S)-2′-benzoyl-1,1′′-dibenzyl-5′-[(5-bromopyridin-2-yl)amino]-5,5′′-difluoro-4′-hydroxy-4′-phenyl-1,1′′,2,2′′-tetrahydrodispiro[indole-3,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (3i′). White solid, Mp: 266–268 °C; IR (KBr): 3375, 3066, 3027, 2863, 2793, 2254, 2204, 1692, 1590, 1497, 1352, 1278, 1188, 1141, 1067, 1013, 966, 696, 532 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.15 (d, J = 8.4 Hz, 1H), 7.75 (s, 1H), 7.72 (d, J = 8.4 Hz, 1H), 7.32–7.08 (m, 20H), 6.91 (s, 1H), 6.84 (d, J = 7.6 Hz, 2H), 6.57 (t, J = 8.4 Hz, 1H), 6.48 (d, J = 7.2 Hz, 2H), 6.33–6.30 (m, 1H), 5.97 (d, J = 8.8 Hz, 1H), 5.94–5.91 (m, 1H), 5.29 (d, J = 16.4 Hz, 2H), 5.19 (d, J = 16.4 Hz, 1H), 4.46 (d, J = 16.0 Hz, 1H), 4.05 (d, J = 15.6 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 195.5, 180.9, 176.3, 160.1 (d, J = 240.63 Hz), 158.7 (d, J = 238.35 Hz), 155.1, 148.4, 139.9, 139.4, 137.8, 136.8, 135.7, 135.2, 133.8, 132.7, 131.5, 131.4, 128.8, 128.6, 128.2, 128.0, 127.9, 127.2, 127.1, 126.6, 126.4, 115.3 (d, J = 23.60 Hz), 115.1 (d, J = 26.47 Hz), 114.6 (d, J = 24.1 Hz), 113.6 (d, J = 25.12 Hz), 109.5 (d, J = 7.93 Hz), 109.4 (d, J = 8.30 Hz), 108.9, 107.8, 86.1, 64.4, 62.72, 62.5, 59.8, 44.5, 44.1; HRMS (EI) calcd for [C₅₁H₃₇BrF₂N₄O₄]⁺: 886.1966; found: 886.1964.

(2′S,3R,3′R,4′R,5′S)-2′-Benzoyl-1,1′′-dibenzyl-5,5′′-difluoro-4′-hydroxy-5′-[(4-methylpyridin-2-yl)amino]-4′-phenyl-1,1′′,2,2′′-tetrahydrodispiro[indole-3,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (3j′). White solid, Mp: 216–218 °C; IR (KBr): 3382, 3089, 3065, 2970, 2914, 1708, 1692, 1622, 1493, 1450, 1372, 1348, 1263, 1181, 1141 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.19 (dd, J = 8.6, 2.5 Hz, 1H), 7.74 (dd, J = 8.3, 2.5 Hz, 1H), 7.66 (d, J = 5.1 Hz, 1H), 7.37–7.21 (m, 5H), 7.22–6.99 (m, 13H), 6.90 (s, 1H), 6.89–6.81 (m, 3H), 6.59–6.53 (m, 1H), 6.50 (d, J = 6.9 Hz, 2H), 6.32 (dd, J = 8.5, 4.2 Hz, 1H), 6.25 (d, J = 5.0 Hz, 1H), 5.90 (dd, J = 8.6, 4.1 Hz, 1H), 5.82 (s, 1H), 5.31 (s, 1H), 5.27 (d, J = 15.9 Hz, 1H), 5.19 (d, J = 16.2 Hz, 1H), 4.47 (d, J = 16.2 Hz, 1H), 4.09 (d, J = 15.9 Hz, 1H), 1.97 (s, 3H). ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 195.6, 191.7, 181.0, 176.5, 159.4 (d, J = 367.0 Hz), 158.3 (d, J = 338.4 Hz), 139.88, 138.1, 136.8, 135.8, 135.2, 133.8, 132.6, 131.7, 128.7, 128.6, 128.0, 128.0, 127.8, 127.6, 127.2, 127.0, 126.7, 126.3, 115.2 (d, J = 22.8 Hz), 114.9 (d, J = 22.1 Hz), 114.5 (d, J = 23.6 Hz), 113.6 (d, J = 24.9 Hz), 109.4 (d, J = 7.9 Hz), 109.4 (d, J = 8.2 Hz) 86.2, 64.5, 63.0, 62.6, 60.1, 44.5, 44.1, 20.9; HRMS (EI) calcd for [C₅₂H₄₀F₂N₄O₄]⁺: 822.3018; found: 822.3016.

(2′S,3R,3′R,4′R,5′S)-2′-Benzoyl-1,1′′-dibenzyl-5′-[(5-chloropyridin-2-yl)amino]-5,5′′-difluoro-4′-hydroxy-4′-phenyl-1,1′′,2,2′′-tetrahydrodispiro[indole-3,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (3k′). White solid, Mp: 252–254 °C; IR (KBr): 3383, 3063, 3027, 1708, 1594, 1497, 1450, 1387, 1348, 1266, 1220, 1173, 1032, 970, 899, 841, 806, 751, 696, 610 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.15 (d, J = 8.4 Hz, 1H), 7.72 (d, J = 8.0 Hz, 1H), 7.67 (s, 1H), 7.32–7.24 (m, 5H), 7.21–7.08 (m, 14H), 6.91 (s, 1H), 6.84 (d, J = 8.0 Hz, 3H), 6.57 (t, J = 8.8 Hz, 1H), 6.49 (d, J = 7.6 Hz, 2H), 6.31 (dd, J = 4.0 Hz, 4.0 Hz, 1H), 6.00 (d, J = 8.8 Hz, 1H), 5.92 (dd, J = 4.0 Hz, 4.0 Hz, 1H), 5.30 (d, J = 4.8 Hz, 1H), 5.27 (d, J = 5.6 Hz, 1H), 5.17 (d, J = 16.4 Hz, 1H), 4.46 (d, J = 16.4 Hz, 1H), 4.06 (d, J = 16.0 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 195.5, 181.0, 176.3, 160.1 (d, J = 240.6 Hz), 158.7 (d, J = 238.28 Hz), 154.8, 146.2, 139.9, 137.8, 136.8, 135.7, 135.2, 133.8, 132.7, 128.2, 128.0, 127.8, 127.2, 127.0, 126.6, 126.4, 120.3, 115.3 (d, J = 23.4 Hz), 115.1 (d, J = 26.44 Hz), 114.6 (d, J = 17.1 Hz), 113.6 (d, J = 25.13 Hz), 109.5 (d, J = 8.05 Hz), 109.4 (d, J = 8.22 Hz), 108.3, 86.2, 64.4, 62.7, 62.5, 58.9, 44.5, 44.1; HRMS (EI) calcd for [C₅₁H₃₇ClF₂N₄O₄]⁺: 842.2471; found: 842.2470.

(2′S,3R,3′R,4′R,5′S)-2′-Benzoyl-1,1′′-dibenzyl-5,5′′-difluoro-4′-hydroxy-4′-phenyl-5′-[(pyrazin-2-yl)amino]-1,1′′,2,2′′-tetrahydrodispiro[indole-3,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (3l′). White solid, Mp: 288–290 °C; IR (KBr): 3371, 3066, 1704, 1692, 1657, 1583, 1540, 1493, 1446, 1354, 1333, 1270, 1177, 1075, 1001, 977, 899, 806, 751, 692, 610, 560, 540, 458, 423 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.18 (dd, J = 8.6, 2.5 Hz, 1H), 7.73 (dd, J = 8.3, 2.5 Hz, 1H), 7.65–7.60 (m, 2H), 7.59 (s, 1H), 7.36–7.22 (m, 5H), 7.19–7.06 (m, 12H), 6.97 (s, 1H), 6.84 (d, J = 7.7 Hz, 3H), 6.60–6.53 (m, 1H), 6.50 (d, J = 7.0 Hz, 2H), 6.32 (dd, J = 8.6, 4.2 Hz, 1H), 5.95 (dd, J = 8.6, 4.1 Hz, 1H), 5.44 (d, J = 8.9 Hz, 1H), 5.29 (s, 1H), 5.27 (d, J = 18.1 Hz, 1H), 5.18 (d, J = 16.2 Hz, 1H), 4.47 (d, J = 16.2 Hz, 1H), 4.08 (d, J = 15.8 Hz, 1H). ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 195.4, 180.9, 176.2, 160.1 (d, J = 241.4 Hz), 158.7 (d, J = 238.4 Hz), 152.7, 141.7, 139.8, 137.7, 136.8, 135.5, 135.1, 133.8, 133.6, 132.7, 132.2, 131.2, 131.1, 128.9, 128.6, 128.2, 127.9, 127.9, 127.9, 127.8, 127.1, 127.0, 126.6, 126.4, 126.3, 115.3 (d, J = 23.1 Hz), 114.9 (d, J = 41.5 Hz), 114.3 (d, J = 44.6 Hz), 113.6 (d, J = 25.0 Hz), 109.5 (d, J = 8.0 Hz), 109.1 (d, J = 8.3 Hz) 86.1, 64.4, 62.6, 61.3, 59.7, 44.4, 44.0; HRMS (EI) calcd for [C₅₀H₃₇F₂N₅O₄]⁺: 809.2814; found: 808.2812.

(1′R,2′S,3R,4′R,5′S)-1,1′′-Dibenzyl-4′-hydroxy-2′-(4-methoxybenzoyl)-4′-(4-methoxyphenyl)-5′-[(pyrazin-2-yl)amino]-1,1′′,2,2′′-tetrahydrodispiro[indole-3,3′-cyclopentane-1′,3′′-indole]-2,2′′-dione (3m′). White solid, Mp: 288–290 °C; IR (KBr): 3375, 3281, 3063, 2938, 2840, 1708, 1676, 1610, 1602, 1516, 1497, 1466, 1387, 1368, 1259, 1181, 1106, 1028, 841, 806, 751, 700, 509, 474 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.28 (d, J = 7.6 Hz, 1H), 7.93 (d, J = 7.2 Hz, 1H), 7.61 (s, 2H), 7.51 (s, 1H), 7.31–7.04 (m, 13H), 6.95 (t, J = 8.4 Hz, 4H), 6.88 (b, s, 2H), 6.57 (d, J = 8.4 Hz, 2H), 6.52 (d, J = 8.0 Hz, 4H), 6.43 (d, J = 7.2 Hz, 1H), 6.13 (d, J = 7.6 Hz, 1H), 5.35 (d, J = 14.0 Hz, 1H), 5.29 (s, 1H), 5.22 (d, J = 16.0 Hz, 1H), 4.45 (d, J = 16.0 Hz, 1H), 4.27 (d, J = 15.6 Hz, 1H), 3.72 (s, 3H), 3.70 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 193.8, 181.3, 176.7, 163.0, 159.3, 153.0, 143.9, 141.7, 135.5, 134.3, 133.5, 131.9, 129.8, 129.5, 128.8, 128.3, 127.9, 127.8, 127.2, 126.9, 126.7, 126.5, 125.5, 124.2, 121.9, 113.1, 108.9, 108.5, 85.8, 64.2, 62.0, 59.7, 55.4, 54.9, 44.3, 43.8; HRMS (EI) calcd for [C₅₂H₄₃N₅O₆]⁺: 833.3213; found: 833.3212.

(2′S,3R,3′R,4′R,5′S)-2′-Benzoyl-5′-[(1,3-benzothiazol-2-yl)amino]-1,1′′-dibenzyl-4′-hydroxy-4′-phenyl-1,1′′,2,2′′-tetrahydrodispiro[indole-3,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (3n′). White solid, Mp: 240–242 °C; IR (KBr): 2914, 1708, 1692, 1622, 1493, 1450, 1372, 1348, 1263, 1181, 1141, 981, 895, 845, 802, 747, 692, 610, 560, 462 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.35 (d, J = 7.5 Hz, 1H), 7.96 (d, J = 6.7 Hz, 1H), 7.39 (d, J = 7.8 Hz, 1H), 7.30–7.25 (m, 2H), 7.20 (t, J = 7.0 Hz, 5H), 7.17–7.06 (m, 10H), 7.06–7.00 (m, 3H), 6.98 (d, J = 7.9 Hz, 1H), 6.95 (s, 1H), 6.89 (q, J = 8.7 Hz, 5H), 6.82 (s, 1H), 6.53 (d, J = 6.9 Hz, 2H), 6.41 (d, J = 7.3 Hz, 1H), 6.01 (d, J = 7.8 Hz, 1H), 5.38 (s, 1H), 5.27 (d, J = 15.8 Hz, 1H), 5.18 (d, J = 16.2 Hz, 1H), 4.50 (d, J = 16.2 Hz, 1H), 4.15 (d, J = 15.8 Hz, 1H). ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 195.6, 180.7, 176.5, 165.7, 152.0, 143.8, 142.1, 136.9, 135.4, 133.8, 132.4, 131.0, 129.5, 129.0, 128.7, 128.6, 128.5, 128.1, 127.9, 127.8, 127.5, 127.1, 127.1, 126.9, 126.6, 126.3, 126.1, 125.7, 125.4, 124.3, 122.1, 121.6, 120.6, 119.3, 109.0, 109.0, 86.0, 66.8, 63.9, 62.5, 59.3, 44.5, 43.9; HRMS (EI) calcd for [C₅₃H₄₀N₄O₄S]⁺: 828.2770; found: 828.2768.

General procedure for the preparation of compounds 5a–t

Procedure 3. With slight modification of procedure 2 and using 0.5 mmol 3-phenacylidineoxindole, 0.5 mmol phenacylacenaphthylenone, 10 mL ethanol and 5 mol% DIPEA only a single product was obtained. The crude product was separated by filtration, washed with 10–15 mL of ethanol to obtain pure white solid that did not require further purification.

(1R,2′S,3′R,4′R)-2′-Benzoyl-1′′-benzyl-4′-hydroxy-4′-(4-phenylphenyl)-1′′,2′′-dihydro-2H-dispiro[acenaphthylene-1,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (5a). White solid, Mp: 254–256 °C; IR (KBr): 3397, 3057, 2930, 1713, 1694, 1601, 1489, 1462, 1423, 1365, 1234, 1180, 1103, 1079, 1037, 1002, 956, 832, 790, 732, 751, 701, 654, 608, 573, 519, 461 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.51 (s, 1H), 8.01 (d, J = 6.9 Hz, 2H), 7.90 (d, J = 8.0 Hz, 1H), 7.60 (d, J = 7.8 Hz, 3H), 7.57 (d, J = 7.7 Hz, 2H), 7.43 (d, J = 6.9 Hz, 4H), 7.37–7.31 (m, 1H), 7.27 (d, J = 8.1 Hz, 3H), 7.18–7.09 (m, 2H), 6.96 (dd, J = 18.3, 8.3 Hz, 5H), 6.82 (t, J = 7.2 Hz, 1H), 6.65 (dd, J = 14.0, 6.4 Hz, 2H), 6.61 (s, 2H), 6.44 (d, J = 7.2 Hz, 1H), 5.40 (s, 1H), 5.27 (d, J = 16.1 Hz, 1H), 4.65 (d, J = 14.1 Hz, 1H), 4.49 (d, J = 15.9 Hz, 1H), 2.60 (d, J = 14.1 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 213.0, 197.0, 177.1, 143.9, 142.1, 140.5, 140.3, 139.8, 137.5, 136.5, 135.7, 133.0, 131.5, 131.3, 129.9, 129.6, 128.7, 128.7, 128.5, 127.7, 127.3, 127.2, 127.0, 126.8, 126.8, 126.7, 126.5, 126.4, 126.2, 125.7, 124.9, 124.4, 122.7, 121.9, 108.9, 84.4, 67.0, 66.2, 59.4, 46.8, 43.9; HRMS (EI) calcd for [C₄₉H₃₄NO₄]⁺: 701.2566; found: 701.2564.

(1R,2′S,3′R,4′R)-1′′-Benzyl-4′-hydroxy-2′-(4-methylbenzoyl)-4′-(4-phenylphenyl)-1′′,2′′-dihydro-2H-dispiro[acenaphthylene-1,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (5b). White solid, Mp: 240–242 °C; IR (KBr): 3369, 3023, 1711, 1688, 1596, 1488, 1423, 1350, 1273, 1230, 1207, 1173, 1103, 1003, 961, 819, 784, 750, 696, 638, 573, 519, 461, 423 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.46 (d, J = 5.8 Hz, 1H), 8.03 (d, J = 7.0 Hz, 1H), 7.99 (s, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.67–7.55 (m, 5H), 7.44 (dd, J = 11.8, 7.8 Hz, 4H), 7.36 (d, J = 7.3 Hz, 1H), 7.31 (d, J = 8.2 Hz, 3H), 7.10 (d, J = 8.2 Hz, 1H), 6.97 (dt, J = 14.3, 7.2 Hz, 3H), 6.83 (d, J = 7.7 Hz, 2H), 6.65 (s, 1H), 6.57 (d, J = 7.2 Hz, 2H), 6.45 (d, J = 7.7 Hz, 2H), 6.32 (d, J = 8.3 Hz, 1H), 5.30 (s, 1H), 5.26 (d, J = 16.3 Hz, 1H), 4.62 (d, J = 14.2 Hz, 1H), 4.45 (d, J = 16.1 Hz, 1H), 2.59 (d, J = 14.2 Hz, 1H), 1.93 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 212.9, 196.5, 176.7, 142.5, 142.5, 142.1, 140.4, 140.4, 139.6, 137.3, 135.2, 133.7, 132.9, 131.3, 129.9, 129.5, 128.7, 128.7, 128.6, 127.9, 127.6, 127.4, 127.2, 127.0, 126.7, 126.7, 126.3, 126.1, 124.7, 124.4, 122.8, 109.7, 84.4, 67.2, 66.5, 59.4, 46.7, 44.0, 21.1; HRMS (EI) calcd for [C₅₀H₃₇NO₄]⁺: 715.2723; found: 715.2721.

(1R,2′S,3′R,4′R)-1′′-Benzyl-4′-hydroxy-2′-(4-methoxybenzoyl)-4′-(4-phenylphenyl)-1′′,2′′-dihydro-2H-dispiro[acenaphthylene-1,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (5c). White solid, Mp: 246–248 °C; IR (KBr): 3380, 3057, 2923, 2842, 1946, 1696, 1600, 1492, 1350, 1261, 1230, 1173, 1034, 1007, 842, 753, 696, 646, 553, 515, 492, 450 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.49 (d, J = 3.8 Hz, 1H), 8.04 (d, J = 6.8 Hz, 1H), 7.99 (d, J = 6.8 Hz, 1H), 7.94 (d, J = 7.9 Hz, 1H), 7.63 (d, J = 13.2 Hz, 3H), 7.56 (d, J = 7.3 Hz, 2H), 7.41 (d, J = 3.9 Hz, 4H), 7.34 (d, J = 7.0 Hz, 1H), 7.26 (d, J = 8.3 Hz, 2H), 7.18–7.04 (m, 2H), 6.96 (d, J = 6.7 Hz, 5H), 6.59 (s, 3H), 6.43 (d, J = 7.0 Hz, 1H), 6.15 (d, J = 8.2 Hz, 2H), 5.36 (s, 1H), 5.29 (d, J = 16.0 Hz, 1H), 4.66 (d, J = 14.1 Hz, 1H), 4.47 (d, J = 16.0 Hz, 1H), 3.50 (s, 3H), 2.60 (d, J = 14.1 Hz, 1H). ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 213.3, 195.1, 177.2, 162.2, 143.9, 142.1, 140.5, 140.2, 139.9, 137.6, 135.7, 133.0, 131.3, 129.9, 129.6, 129.4, 128.8, 128.7, 128.6, 128.5, 127.6, 127.3, 127.0, 126.8, 126.8, 126.7, 126.3, 126.2, 125.7, 124.9, 124.3, 122.7, 121.8, 112.5, 108.8, 84.4, 67.0, 66.0, 59.6, 55.1, 46.8, 43.9; HRMS (EI) calcd for [C₅₀H₃₇NO₅]⁺: 731.2672; found: 731.2670.

(1R,2′S,3′R,4′R)-1′′-Benzyl-2′-(4-bromobenzoyl)-4′-hydroxy-4′-(4-phenylphenyl)-1′′,2′′-dihydro-2H-dispiro[acenaphthylene-1,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (5d). White solid, Mp: 250–252 °C; IR (KBr): 3387, 3056, 3033, 1701, 1605, 1578, 1489, 1462, 1416, 1362, 1235, 1177, 1070, 996, 958, 835, 785, 754, 696, 642, 515, 465 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.51 (d, J = 6.6 Hz, 1H), 8.04 (d, J = 7.0 Hz, 1H), 7.98 (t, J = 7.0 Hz, 2H), 7.74–7.59 (m, 3H), 7.56 (d, J = 7.5 Hz, 2H), 7.43 (d, J = 6.7 Hz, 4H), 7.34 (t, J = 6.5 Hz, 1H), 7.26 (d, J = 7.7 Hz, 2H), 7.12 (dd, J = 15.7, 7.7 Hz, 2H), 7.04–6.90 (m, 3H), 6.85–6.68 (m, 4H), 6.61 (d, J = 7.0 Hz, 2H), 6.57 (s, 1H), 6.44 (d, J = 7.2 Hz, 1H), 5.29 (s, 1H), 5.24 (d, J = 16.0 Hz, 1H), 4.64 (d, J = 14.1 Hz, 1H), 4.49 (d, J = 16.0 Hz, 1H), 2.60 (d, J = 14.1 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 212.9, 196.1, 176.9, 143.9, 142.1, 140.4, 140.3, 139.6, 137.4, 135.5, 135.3, 133.4, 131.1, 130.4, 129.9, 129.6, 128.8, 128.7, 128.5, 127.9, 127.8, 127.3, 127.0, 126.8, 126.6, 126.6, 126.4, 126.3, 126.2, 125.7, 124.8, 124.6, 122.9, 121.9, 108.9, 84.4, 66.9, 66.4, 59.4, 46.5, 43.9; HRMS (EI) calcd for [C₄₉H₃₄BrNO₄]⁺: 779.1671; found: 779.1671.

(1R,2′S,3′R,4′R)-2′-Benzoyl-1′′-benzyl-5′′-fluoro-4′-hydroxy-4′-(4-phenylphenyl)-1′′,2′′-dihydro-2H-dispiro[acenaphthylene-1,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (5e). White solid, Mp: 240–242 °C; IR (KBr): 3557, 3369, 3061, 2927, 1711, 1688, 1600, 1488, 1446, 1419, 1350, 1273, 1234, 1173, 1134, 1100, 1000, 961, 788, 765, 696, 519 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.50 (t, J = 3.8 Hz, 1H), 8.02 (d, J = 7.0 Hz, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.78 (d, J = 8.3 Hz, 1H), 7.68–7.55 (m, 5H), 7.44 (t, J = 9.3 Hz, 4H), 7.33 (dd, J = 17.8, 7.7 Hz, 3H), 7.08–6.89 (m, 5H), 6.82 (d, J = 7.7 Hz, 2H), 6.72–6.62 (m, 3H), 6.59 (d, J = 7.3 Hz, 2H), 6.32 (dd, J = 8.5, 4.2 Hz, 1H), 5.32 (s, 1H), 5.26 (d, J = 16.1 Hz, 1H), 4.63 (d, J = 14.3 Hz, 1H), 4.47 (d, J = 16.1 Hz, 1H), 2.60 (d, J = 14.2 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 212.9, 196.9, 176.8, 157.5, 142.1, 140.4, 140.4, 139.8, 139.6, 137.3, 136.3, 135.3, 133.1, 131.6, 131.2, 129.9, 129.5, 128.7, 128.5, 127.7, 127.4, 127.3, 127.0, 126.9, 126.7, 126.5, 126.3, 126.3, 124.8, 124.5, 122.8, 115.0, 114.8, 114.0, 113.7, 109.3, 109.2, 84.4, 67.4, 66.4, 59.4, 46.7, 44.0, 29.7; HRMS (EI) calcd for [C₄₉H₃₄FNO₄]⁺: 719.2472; found: 719.2470.

(1R,2′S,3′R,4′R)-2′-Benzoyl-1′′-benzyl-5′′-chloro-4′-hydroxy-4′-(4-phenylphenyl)-1′′,2′′-dihydro-2H-dispiro[acenaphthylene-1,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (5f). White solid, Mp: 258–260 °C; IR (KBr): 3396, 3057, 2934, 1711, 1677, 1627, 1600, 1492, 1465, 1434, 1369, 1350, 1238, 1130, 1011, 930, 857, 830, 784, 669, 600, 534, 480 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.48 (s, 1H), 8.09–7.97 (m, 2H), 7.91 (d, J = 8.0 Hz, 1H), 7.68–7.54 (m, 6H), 7.44 (dd, J = 11.7, 7.8 Hz, 5H), 7.34 (dd, J = 18.1, 7.6 Hz, 4H), 7.11 (d, J = 8.1 Hz, 1H), 7.05–6.90 (m, 6H), 6.83 (t, J = 7.3 Hz, 1H), 6.73–6.63 (m, 4H), 6.58 (d, J = 7.1 Hz, 2H), 6.33 (d, J = 8.2 Hz, 1H), 5.32 (s, 1H), 5.25 (d, J = 16.1 Hz, 1H), 4.62 (d, J = 14.3 Hz, 1H), 4.47 (d, J = 16.1 Hz, 1H), 2.60 (d, J = 14.2 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 212.8, 196.9, 176.7, 142.5, 142.1, 140.4, 140.4, 139.6, 137.2, 136.2, 135.2, 133.1, 131.7, 131.2, 129.9, 129.5, 128.7, 128.6, 127.7, 127.4, 127.3, 127.0, 126.7, 126.5, 126.3, 126.1, 124.7, 124.5, 122.9, 109.8, 84.4, 67.2, 66.4, 59.3, 46.7, 44.0; HRMS (EI) calcd for [C₄₉H₃₄ClNO₄]⁺: 735.2176; found: 735.2175.

(1R,2′S,3′R,4′R)-1′′-Benzyl-5′′-chloro-4′-hydroxy-2′-(4-methylbenzoyl)-4′-(4-phenylphenyl)-1′′,2′′-dihydro-2H-dispiro[acenaphthylene-1,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (5g). White solid, Mp: 254–256 °C; IR (KBr): 3553, 3373, 3034, 2927, 1711, 1684, 1603, 1488, 1423, 1346, 1234, 1177, 1119, 1003, 967, 919, 830, 784, 765, 700, 646, 596, 569, 523, 465, 419 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.47 (d, J = 5.9 Hz, 1H), 8.03 (d, J = 6.9 Hz, 1H), 7.99 (s, 1H), 7.91 (d, J = 8.1 Hz, 1H), 7.68–7.53 (m, 5H), 7.44 (dd, J = 11.6, 7.5 Hz, 4H), 7.36 (d, J = 7.0 Hz, 1H), 7.31 (d, J = 7.7 Hz, 2H), 7.10 (d, J = 8.3 Hz, 1H), 6.98 (dt, J = 14.5, 7.8 Hz, 3H), 6.83 (d, J = 7.3 Hz, 2H), 6.65 (s, 1H), 6.57 (d, J = 7.3 Hz, 2H), 6.45 (d, J = 7.5 Hz, 2H), 6.32 (d, J = 8.2 Hz, 1H), 4.62 (d, J = 14.2 Hz, 1H), 4.45 (d, J = 16.1 Hz, 1H), 2.59 (d, J = 14.2 Hz, 1H), 1.94 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 212.9, 196.5, 176.7, 142.5, 142.5, 142.1, 140.4, 140.4, 139.6, 137.3, 135.2, 133.7, 132.9, 131.3, 129.9, 129.5, 128.7, 128.7, 128.6, 127.9, 127.6, 127.4, 127.2, 127.0, 127.0, 126.7, 126.3, 126.1, 124.7, 124.4, 122.8, 109.7, 84.4, 67.2, 66.5, 59.5, 46.7, 44.0, 21.1; HRMS (EI) calcd for [C₅₀H₃₆ClNO₄]⁺: 749.2333; found: 749.2333.

(1R,2′S,3′R,4′R)-2′-Benzoyl-4′-hydroxy-1′′-methyl-4′-(4-phenylphenyl)-1′′,2′′-dihydro-2H-dispiro[acenaphthylene-1,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (5h). White solid, Mp: 244–246 °C; IR (KBr): 3334, 3053, 2927, 2857, 1703, 1688, 1607, 1492, 1469, 1430, 1346, 1234, 1123, 1096, 1007, 965, 923, 830, 780, 757, 696, 646, 600 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.57 (d, J = 5.8 Hz, 1H), 8.05 (d, J = 7.0 Hz, 1H), 7.94 (d, J = 7.1 Hz, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.60 (t, J = 6.1 Hz, 2H), 7.53 (d, J = 7.4 Hz, 1H), 7.43–7.28 (m, 7H), 7.18 (d, J = 9.4 Hz, 5H), 6.96 (d, J = 7.7 Hz, 2H), 6.82 (d, J = 7.8 Hz, 2H), 6.66 (d, J = 7.5 Hz, 1H), 6.57 (s, 1H), 5.33 (s, 1H), 4.57 (d, J = 14.1 Hz, 1H), 2.96 (s, 3H), 2.58 (d, J = 14.2 Hz, 1H). ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 213.2, 196.5, 176.8, 144.5, 144.2, 142.2, 140.6, 140.1, 139.9, 139.6, 137.0, 135.3, 133.1, 131.4, 129.9, 129.6, 128.7, 127.9, 127.6, 127.2, 126.9, 126.9, 126.7, 126.2, 125.8, 125.8, 125.6, 124.9, 124.4, 122.7, 121.8, 107.5, 84.5, 67.5, 65.3, 59.6, 46.2, 25.9; HRMS (EI) calcd for [C₄₃H₃₁NO₄]⁺: 625.2253; found: 625.2253.

(1R,2′S,3′R,4′R)-2′-Benzoyl-4′-hydroxy-1′′-[(3-methylphenyl)methyl]-4′-(4-phenylphenyl)-1′′,2′′-dihydro-2H-dispiro[acenaphthylene-1,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (5i). White solid, Mp: 256–258 °C; IR (KBr): 3394, 3052, 2931, 1715, 1674, 1623, 1600, 1497, 1455, 1424, 1360, 1352, 1248, 1130, 1021, 934, 852, 828, 774, 670, 602, 536, 482 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.46 (d, J = 6.4 Hz, 1H), 8.25 (d, J = 7.2 Hz, 1H), 8.08 (d, J = 6.9 Hz, 1H), 7.96 (d, J = 8.0 Hz, 1H), 7.89–7.83 (m, 2H), 7.80 (d, J = 7.0 Hz, 1H), 7.77–7.71 (m, 1H), 7.60 (td, J = 16.4, 8.0 Hz, 5H), 7.42–7.29 (m, 8H), 7.13 (d, J = 6.8 Hz, 3H), 7.06 (d, J = 7.6 Hz, 2H), 6.94 (d, J = 8.1 Hz, 2H), 6.81 (d, J = 7.4 Hz, 2H), 6.73 (s, 1H), 5.63 (s, 1H), 4.61 (d, J = 13.9 Hz, 1H), 2.73 (d, J = 13.7 Hz, 1H), 2.18 (s, 3H); ¹³C NMR: (100 MHz, CDCl₃): δ (ppm) 212.9, 196.5, 176.7, 142.5, 142.4, 142.1, 140.4, 140.4, 139.6, 137.3, 135.2, 133.7, 132.9, 131.3, 129.9, 129.5, 128.7, 128.7, 128.6, 127.9, 127.6, 127.4, 127.2, 127.0, 127.0, 126.7, 126.6, 126.3, 126.1, 124.7, 124.4, 122.8, 109.7, 84.4, 77.3, 77.0, 76.7, 67.2, 66.5, 59.4, 46.7, 44.0, 21.0; HRMS (EI) calcd for [C₅₀H₃₇NO₄]⁺: 715.2723; found: 715.2723.

(1R,2′S,3′R,4′R)-2′-Benzoyl-4′-(4-bromophenyl)-4′-hydroxy-1′′,2′′-dihydro-2H-dispiro[acenaphthylene-1,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (5j). White solid, Mp: 250–252 °C; IR (KBr, cm⁻¹): 3513, 3455, 2928, 2848, 1702, 1615, 1352, 1262, 1144, 901, 720, 617, 467 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.39 (d, J = 6.7 Hz, 1H), 8.17 (d, J = 6.9 Hz, 1H), 8.06 (d, J = 7.0 Hz, 1H), 7.98 (d, J = 8.0 Hz, 2H), 7.83 (dd, J = 11.1, 7.9 Hz, 2H), 7.70 (dd, J = 11.5, 4.7 Hz, 2H), 7.66 (s, 1H), 7.61 (dd, J = 11.7, 7.2 Hz, 2H), 7.01 (d, J = 8.2 Hz, 2H), 6.88 (d, J = 8.2 Hz, 2H), 6.71 (q, J = 8.3 Hz, 3H), 6.66 (s, 1H), 5.47 (s, 1H), 4.48 (d, J = 14.2 Hz, 1H), 2.64 (d, J = 14.2 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 212.7, 204.3, 196.4, 142.1, 141.6, 139.5, 137.9, 137.4, 137.2, 134.8, 134.1, 133.4, 131.1, 131.0, 130.4, 130.3, 130.2, 130.0, 129.5, 128.1, 127.9, 127.9, 126.6, 125.0, 124.8, 124.4, 124.3, 123.0, 122.8, 121.6, 120.9, 84.2, 71.6, 67.70, 59.6, 47.0; HRMS (EI) calcd for [C₃₆H₂₄BrNO₄]⁺: 613.0889; found: 613.0889.

(1R,2′S,3′R,4′R)-2′-Benzoyl-1′′-benzyl-4′-(4-bromophenyl)-4′-hydroxy-1′′,2′′-dihydro-2H-dispiro[acenaphthylene-1,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (5k). White solid, Mp: 255–257 °C; IR (KBr): 3387, 3047, 2946, 2852, 1740, 1686, 1621, 1492, 1469, 1429, 1419, 1362, 1235, 1210, 1178, 1024, 951, 852, 825, 783, 769, 736, 704, 644, 602, 563, 452 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.46 (s, 1H), 8.10–7.84 (m, 3H), 7.60 (s, 3H), 7.37–7.02 (m, 9H), 6.91 (d, J = 6.7 Hz, 2H), 6.81 (s, 1H), 6.62 (s, 5H), 6.47 (d, J = 7.0 Hz, 1H), 5.34 (s, 1H), 5.29 (d, J = 16.0 Hz, 1H), 4.51 (dd, J = 20.8, 15.6 Hz, 2H), 2.54 (d, J = 14.0 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 212.9, 196.8, 176.9, 143.8, 142.1, 139.6, 137.5, 136.4, 135.6, 133.1, 131.6, 131.1, 130.8, 129.9, 129.5, 128.8, 128.6, 128.1, 127.7, 127.2, 127.1, 126.5, 126.4, 125.7, 124.8, 124.5, 122.8, 122.1, 122.0, 108.9, 84.0, 66.8, 66.12, 59.3, 46.5, 43.9; HRMS (EI) calcd for [C₄₃H₃₀BrNO₄]⁺: 703.1358; found: 703.1358.

(1R,2′S,3′R,4′R)-2′-Benzoyl-4′-(4-bromophenyl)-4′-hydroxy-1′′-[(3-methylphenyl)methyl]-1′′,2′′-dihydro-2H-dispiro[acenaphthylene-1,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (5l). White solid, Mp: 238–240 °C; IR (KBr): 3503, 3450, 2927, 2850, 1700, 1603, 1350, 1261, 1134, 903, 719, 607 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.74 (d, J = 7.2 Hz, 1H), 8.47 (s, 1H), 8.16 (d, J = 8.2 Hz, 1H), 8.11 (d, J = 7.1 Hz, 1H), 8.04 (d, J = 7.3 Hz, 1H), 8.00 (d, J = 7.6 Hz, 1H), 7.94 (d, J = 7.3 Hz, 1H), 7.90 (d, J = 8.2 Hz, 1H), 7.71 (t, J = 8.0 Hz, 1H), 7.61 (d, J = 7.2 Hz, 3H), 7.25 (d, J = 7.1 Hz, 2H), 7.15 (d, J = 7.0 Hz, 1H), 7.11 (s, 1H), 7.07 (d, J = 8.3 Hz, 2H), 7.03 (d, J = 10.2 Hz, 2H), 6.91 (d, J = 7.6 Hz, 2H), 6.81 (t, J = 7.4 Hz, 1H), 6.66 (d, J = 7.5 Hz, 1H), 6.62 (d, J = 7.0 Hz, 1H), 6.49 (d, J = 7.6 Hz, 1H), 6.11 (d, J = 7.6 Hz, 1H), 5.34 (s, 1H), 5.15 (d, J = 16.0 Hz, 1H), 4.51 (t, J = 14.5 Hz, 2H), 2.53 (d, J = 14.1 Hz, 1H), 2.33 (s, 3H), 1.25 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 213.0, 196.7, 176.9, 143.9, 142.1, 139.6, 138.0, 137.5, 136.4, 135.6, 133.1, 132.2, 131.9, 131.5, 131.2, 130.7, 130.3, 129.9, 129.5, 128.8, 128.7, 128.4, 128.0, 127.9, 127.7, 127.6, 127.2, 126.5, 126.4, 125.6, 125.5, 124.8, 124.5, 123.2, 122.8, 122.1, 121.9, 108.9, 84.0, 66.8, 66.0, 59.3, 46.6, 44.0, 21.5; HRMS (EI) calcd for [C₄₄H₃₂BrNO₄]⁺: 717.1515; found: 717.1511.

(1R,2′S,3′R,4′R)-1′′-Benzyl-4′-(4-bromophenyl)-4′-hydroxy-2′-(4-methoxybenzoyl)-1′′,2′′-dihydro-2H-dispiro[acenaphthylene-1,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (5m). White solid, Mp: 242–244 °C; IR (KBr): 3359, 2926, 2848, 1656, 1604, 1480, 1264, 1169, 1021, 926, 786, 609, 544, 472, 406 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.44 (d, J = 6.1 Hz, 1H), 8.03 (d, J = 7.1 Hz, 1H), 7.98–7.90 (m, 2H), 7.67–7.54 (m, 3H), 7.30–7.19 (m, 5H), 7.14 (t, J = 7.5 Hz, 1H), 7.08 (t, J = 6.7 Hz, 3H), 6.94 (d, J = 8.4 Hz, 2H), 6.61 (d, J = 10.1 Hz, 3H), 6.46 (d, J = 7.6 Hz, 1H), 6.14 (d, J = 8.4 Hz, 2H), 5.30 (t, J = 7.9 Hz, 2H), 4.56 (d, J = 14.1 Hz, 1H), 4.47 (d, J = 15.9 Hz, 1H), 3.50 (s, 3H), 2.54 (d, J = 14.1 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 213.2, 195.0, 177.0, 162.3, 143.8, 142.1, 139.6, 137.6, 135.6, 133.1, 130.8, 129.9, 129.6, 129.3, 128.8, 128.6, 128.1, 127.6, 127.0, 126.4, 125.7, 124.8, 124.4, 122.7, 122.1, 121.9, 112.5, 108.8, 84.0, 66.8, 65.90, 59.5, 55.1, 46.5, 43.9; HRMS (EI) calcd for [C₄₄H₃₂BrNO₅]⁺: 733.1464; found: 733.1464.

(1R,2′S,3′R,4′R)-2′-Benzoyl-4′-(4-bromophenyl)-4′-hydroxy-1′′-(prop-2-yn-1-yl)-1′′,2′′-dihydro-2H-dispiro[acenaphthylene-1,1′-cyclopentane-3′,3′′-indole]-2,2′′-dione (5n). White solid, Mp: 238–240 °C; IR (KBr): 3342, 2926, 2857, 2340, 1715, 1666, 1604, 1267, 1123, 1097, 926, 900, 779, 697, 658, 530, 432 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.39 (d, J = 6.7 Hz, 1H), 8.17 (d, J = 6.9 Hz, 1H), 8.06 (d, J = 7.0 Hz, 1H), 7.99 (d, J = 7.9 Hz, 2H), 7.87–7.78 (m, 2H), 7.69 (d, J = 7.6 Hz, 2H), 7.66 (s, 1H), 7.61 (s, 2H), 7.01 (d, J = 8.1 Hz, 3H), 6.88 (d, J = 8.3 Hz, 3H), 6.71 (dd, J = 17.3, 9.4 Hz, 5H), 5.47 (s, 1H), 4.49 (d, J = 14.1 Hz, 1H), 2.65 (d, J = 14.2 Hz, 1H), 1.25 (s, 2H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 212.8, 204.3, 196.4, 142.1, 139.5, 137.3, 134.7, 134.0, 133.4, 131.0, 130.4, 130.3, 129.9, 129.5, 128.1, 128.0, 127.9, 127.9, 126.6, 125.0, 124.8, 124.4, 123.1, 122.8, 120.9, 84.2, 71.6, 67.7, 59.6, 46.9, 29.7; HRMS (EI) calcd for [C₃₉H₂₆BrNO₄]⁺: 651.1045; found: 651.1045.

Methyl(1R,2′S,3′R,4′R)-1′′-benzyl-4′-hydroxy-2,2′′-dioxo-4′-(4-phenylphenyl)-1′′,2′′-dihydro-2H-dispiro[acenaphthylene-1,1′-cyclopentane-3′,3′′-indole]-2′-carboxylate (5o). White solid, Mp: 266–268 °C; IR (KBr): 3557, 3380, 1746, 1711, 1688, 1607, 1492, 1465, 1423, 1365, 1200, 1177, 1138, 1103, 1015, 961, 834, 784, 753, 700, 650, 603, 523 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.60 (d, J = 7.0 Hz, 1H), 8.23 (d, J = 8.1 Hz, 1H), 8.16 (d, J = 7.0 Hz, 1H), 7.94 (d, J = 7.0 Hz, 1H), 7.89 (d, J = 8.3 Hz, 1H), 7.82 (t, J = 7.5 Hz, 1H), 7.75 (t, J = 7.7 Hz, 1H), 7.55 (d, J = 7.5 Hz, 2H), 7.42 (t, J = 7.4 Hz, 3H), 7.33 (t, J = 7.2 Hz, 1H), 7.25 (d, J = 7.2 Hz, 2H), 7.20–7.10 (m, 2H), 6.95 (dt, J = 14.2, 7.0 Hz, 2H), 6.55 (d, J = 7.2 Hz, 1H), 6.45 (s, 1H), 6.42 (d, J = 7.2 Hz, 1H), 5.16 (d, J = 16.1 Hz, 1H), 4.59 (d, J = 8.8 Hz, 1H), 4.40 (d, J = 16.1 Hz, 1H), 2.70 (s, 3H), 2.58 (d, J = 14.2 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 212.0, 176.3, 169.0, 143.7, 142.8, 141.1, 140.4, 140.3, 137.4, 135.4, 133.1, 130.6, 130.3, 129.7, 128.8, 128.7, 128.5, 128.1, 127.3, 127.0, 126.9, 126.5, 126.5, 126.3, 126.3, 126.1, 124.5, 123.3, 122.1, 108.8, 84.8, 67.0, 61.6, 59.5, 51.2, 46.4, 43.7; HRMS (EI) calcd for [C₄₄H₃₃NO₅]⁺: 655.2359; found: 655.2359.

Ethyl(1R,2′S,3′R,4′R)-1′′-benzyl-4′-hydroxy-2,2′′-dioxo-4′-(4-phenylphenyl)-1′′,2′′-dihydro-2H-dispiro[acenaphthylene-1,1′-cyclopentane-3′,3′′-indole]-2′-carboxylate (5p). White solid, Mp: 256–258 °C; IR (KBr): 3335, 3057, 2921, 2850, 1705, 169, 1603, 1492, 1425, 1350, 1237, 1175, 1073, 1013, 967, 826, 788, 745, 696, 650, 520, 453 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.82 (d, J = 7.0 Hz, 1H), 8.39 (d, J = 8.1 Hz, 1H), 8.32 (d, J = 7.0 Hz, 1H), 8.11 (d, J = 7.0 Hz, 1H), 8.06 (d, J = 8.3 Hz, 1H), 7.98 (t, J = 7.6 Hz, 1H), 7.92 (t, J = 7.7 Hz, 1H), 7.72 (d, J = 7.5 Hz, 2H), 7.58 (d, J = 7.6 Hz, 1H), 7.51 (d, J = 7.3 Hz, 1H), 7.43 (d, J = 6.7 Hz, 2H), 7.32 (p, J = 7.4 Hz, 2H), 7.11 (dt, J = 14.4, 7.1 Hz, 2H), 6.70 (d, J = 7.3 Hz, 2H), 6.61 (s, 1H), 6.59 (d, J = 7.2 Hz, 1H), 5.35 (d, J = 16.0 Hz, 1H), 4.77 (d, J = 14.2 Hz, 1H), 4.73 (s, 1H), 4.55 (d, J = 16.1 Hz, 1H), 3.41 (dd, J = 15.1, 7.3 Hz, 2H), 2.76 (d, J = 14.2 Hz, 1H), 0.16 (t, J = 7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 212.3, 176.3, 168.4, 143.7, 143.1, 141.19, 140.4, 140.3, 137.5, 135.4, 133.0, 130.8, 130.4, 129.8, 128.7, 128.5, 128.1, 127.3, 127.0, 126.8, 126.6, 126.6, 126.3, 126.1, 124.4, 123.6, 123.2, 122.1, 108.8, 84.7, 66.9, 61.7, 60.3, 59.5, 46.4, 43.8, 12.6; HRMS (EI) calcd for [C₄₅H₃₅NO₅]⁺: 669.2515; found: 669.2515.

Methyl(1R,2′S,3′R,4′R)-4′-hydroxy-2,2′′-dioxo-4′-(4-phenylphenyl)-1′′-(prop-2-yn-1-yl)-1′′,2′′-dihydro-2H-dispiro[acenaphthylene-1,1′-cyclopentane-3′,3′′-indole]-2′-carboxylate (5q). White solid, Mp: 260–262 °C; IR (KBr): 3395, 3307, 2925, 1739, 1709, 1609, 1493, 1466, 1424, 1362, 1343, 1212, 1177, 1139, 1104, 1008, 962, 927, 788, 754, 700, 661 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.58 (d, J = 7.0 Hz, 1H), 8.24 (d, J = 8.2 Hz, 1H), 8.16 (d, J = 7.1 Hz, 1H), 7.89 (t, J = 6.2 Hz, 2H), 7.83 (t, J = 7.5 Hz, 1H), 7.75 (t, J = 7.7 Hz, 1H), 7.49 (d, J = 7.6 Hz, 2H), 7.36 (dd, J = 18.0, 8.4 Hz, 5H), 7.30 (d, J = 7.0 Hz, 1H), 7.21 (t, J = 7.5 Hz, 1H), 7.12 (d, J = 7.4 Hz, 2H), 6.83 (d, J = 7.7 Hz, 1H), 6.41 (s, 1H), 4.54 (s, 1H), 4.48 (d, J = 14.3 Hz, 1H), 4.42 (d, J = 17.6 Hz, 1H), 4.07 (d, J = 17.7 Hz, 1H), 2.72 (s, 3H), 2.56 (d, J = 14.3 Hz, 1H), 1.76 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 212.0, 175.1, 169.1, 142.9, 142.4, 141.0, 140.7, 140.3, 136.7, 133.1, 130.6, 130.3, 129.7, 128.8, 128.7, 128.1, 127.1, 126.8, 126.2, 126.0, 124.5, 123.3, 123.2, 108.3, 85.0, 71.2, 67.5, 60.5, 59.5, 51.3, 45.8, 28.6; HRMS (EI) calcd for [C₄₀H₂₉NO₅]⁺: 603.2046; found: 603.2044.

Ethyl(1R,2′S,3′R,4′R)-4′-hydroxy-2,2′′-dioxo-4′-(4-phenylphenyl)-1′′-(prop-2-yn-1-yl)-1′′,2′′-dihydro-2H-dispiro[acenaphthylene-1,1′-cyclopentane-3′,3′′-indole]-2′-carboxylate (5r). White solid, Mp: 252–254 °C; IR (KBr): 3503, 3450, 2927, 2850, 1700, 1603, 1350, 1261, 1134, 903, 719, 607, 465 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.63 (d, J = 7.4 Hz, 1H), 8.23 (d, J = 8.2 Hz, 1H), 8.16 (d, J = 7.0 Hz, 1H), 7.89 (t, J = 7.7 Hz, 1H), 7.85–7.80 (m, 1H), 7.76 (d, J = 7.2 Hz, 1H), 7.49 (d, J = 7.2 Hz, 1H), 7.36 (dd, J = 18.7, 7.4 Hz, 4H), 7.19 (s, 1H), 7.12 (d, J = 7.3 Hz, 1H), 6.82 (d, J = 8.0 Hz, 2H), 6.40 (s, 2H), 4.51 (s, 1H), 4.45 (d, J = 16.8 Hz, 1H), 4.03 (d, J = 18.0 Hz, 2H), 3.24 (dd, J = 15.5, 7.8 Hz, 2H), 2.57 (d, J = 14.3 Hz, 2H), 2.18 (s, 2H), 1.74 (s, 1H), 0.88 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 212.1, 174.9, 168.3, 143.1, 142.3, 140.9, 136.7, 133.1, 130.6, 130.5, 130.4, 129.7, 128.9, 128.1, 127.5, 126.0, 125.9, 124.5, 123.5, 123.3, 122.3, 122.1, 108.4, 84.6, 77.3, 77.0, 76.7, 76.4, 71.3, 67.4, 60.4, 59.4, 45.6, 29.7, 28.7, 12.6; HRMS (EI) calcd for [C₄₁H₃₁NO₅]⁺: 617.2202; found: 617.2202.

Ethyl(1R,2′S,3′R,4′R)-4′-(4-bromophenyl)-4′-hydroxy-2,2′′-dioxo-1′′-(prop-2-yn-1-yl)-1′′,2′′-dihydro-2H-dispiro[acenaphthylene-1,1′-cyclopentane-3′,3′′-indole]-2′-carboxylate (5s). White solid, Mp: 255–257 °C; IR (KBr): 3312, 3070, 2939, 1696, 1611, 1480, 1431, 1342, 1179, 1080, 989, 910, 815, 746, 697, 576, 550, 458 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.61 (d, J = 7.0 Hz, 1H), 8.25 (d, J = 8.1 Hz, 1H), 8.16 (s, 1H), 7.92 (d, J = 8.3 Hz, 1H), 7.85 (d, J = 7.6 Hz, 2H), 7.76 (t, J = 7.7 Hz, 1H), 7.37 (t, J = 7.7 Hz, 1H), 7.29 (s, 1H), 7.22 (t, J = 7.4 Hz, 2H), 6.96 (d, J = 8.5 Hz, 2H), 6.85 (d, J = 7.7 Hz, 1H), 6.43 (s, 1H), 4.56 (dd, J = 17.7, 2.3 Hz, 1H), 4.49 (s, 1H), 4.41 (d, J = 14.2 Hz, 1H), 4.02 (dd, J = 17.7, 2.1 Hz, 1H), 3.31–3.17 (m, 2H), 2.53 (d, J = 14.3 Hz, 1H), 2.06 (s, 1H), 0.04–0.01 (m, 3H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 212.1, 174.9, 168.3, 143.1, 142.3, 140.9, 136.7, 133.1, 130.6, 130.5, 130.4, 129.7, 128.9, 128.1, 127.5, 126.0, 125.9, 124.5, 123.5, 123.3, 122.3, 122.1, 108.4, 84.6, 76.4, 71.3, 67.4, 60.4, 59.5, 45.6, 29.7, 28.7, 12.6; HRMS (EI) calcd for [C₃₅H₂₆BrNO₅]⁺: 619.0994; found: 619.0994.

Ethyl(1R,2′S,3′R,4′R)-1′′-benzyl-4′-(4-bromophenyl)-4′-hydroxy-2,2′′-dioxo-1′′,2′′-dihydro-2H-dispiro[acenaphthylene-1,1′-cyclopentane-3′,3′′-indole]-2′-carboxylate (5t). White solid, Mp: 256–258 °C; IR (KBr): 3334, 3057, 2923, 2850, 1707, 1692, 1603, 1492, 1423, 1350, 1234, 1177, 1073, 1011, 967, 826, 788, 746, 696, 650, 523, 457 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.64 (d, J = 7.0 Hz, 1H), 8.27 (d, J = 8.0 Hz, 1H), 8.19 (d, J = 6.8 Hz, 1H), 7.97–7.92 (m, 2H), 7.86 (t, J = 7.6 Hz, 1H), 7.78 (t, J = 7.6 Hz, 1H), 7.33–7.25 (m, 5H), 7.20 (d, J = 7.5 Hz, 1H), 7.16 (d, J = 7.4 Hz, 1H), 7.11 (d, J = 7.9 Hz, 2H), 6.59 (d, J = 7.1 Hz, 2H), 6.50 (d, J = 8.7 Hz, 2H), 5.24 (d, J = 16.0 Hz, 1H), 4.54 (d, J = 14.5 Hz, 2H), 4.42 (d, J = 16.0 Hz, 1H), 3.27 (q, J = 7.2 Hz, 2H), 2.57 (d, J = 14.2 Hz, 1H), 0.07–0.01 (t, J = 7.2 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 212.2, 176.1, 168.3, 143.6, 143.1, 140.9, 137.5, 135.3, 133.1, 130.8, 130.7, 130.3, 129.7, 128.9, 128.6, 128.1, 128.0, 127.1, 126.3, 126.2, 126.0, 124.5, 123.6, 123.3, 122.1, 108.8, 84.4, 66.7, 61.6, 60.3, 59.4, 46.2, 43.8, 12.6; HRMS (EI) calcd for [C₃₉H₃₀BrNO₅]⁺: 671.1307; found: 671.1305.

Acknowledgements

K. Suman thanks the Council of Scientific and Industrial Research (CSIR), New Delhi, India, for Senior Research Fellowship. We thank the Chemical Physics Lab, CLRI for help in recording NMR spectra. Financial support from the CSC0201 project of CSIR is acknowledged.

Notes and references

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17. ESI.†.

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Footnote

† Electronic supplementary information (ESI) available. CCDC 1041757 and 1041758. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5ra00283d

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