Construction of Dispiro-Indenone Scaffolds via Domino Cycloaddition Reactions of α,β-Unsaturated Aldimines with 2-Arylidene-1,3-indenediones and 2,2′-(Arylmethylene)bis(1,3-indenediones)

Wen-Juan Yang; Hui-Lin Fang; Jing Sun; Chao-Guo Yan

doi:10.1021/acsomega.9b01960

. 2019 Aug 7;4(8):13553–13569. doi: 10.1021/acsomega.9b01960

Construction of Dispiro-Indenone Scaffolds via Domino Cycloaddition Reactions of α,β-Unsaturated Aldimines with 2-Arylidene-1,3-indenediones and 2,2′-(Arylmethylene)bis(1,3-indenediones)

Wen-Juan Yang ¹, Hui-Lin Fang ¹, Jing Sun ¹, Chao-Guo Yan ^1,^*

PMCID: PMC6705284 PMID: 31460485

Abstract

The catalyst-free domino reaction of α,β-unsaturated N-alkyl or N-arylaldimines with two molecules of 2-arylidene-1,3-indanediones in dry acetonitrile resulted in polysubstituted spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridines] in moderate to good yields and with high diastereoselectivity. The reaction mechanism included sequential aza/oxa-Diels–Alder reactions via both endo-transition states. On the other hand, the catalyst-free domino reaction of α,β-unsaturated N-arylaldimines with 2,2′-(arylmethylene)bis(1,3-indenediones) afforded the mixed diastereoisomeric dispiro[indene-2,1′-cyclohexane-3′,2″-indene] derivatives in satisfactory yields. The reaction mechanism of this formal [3 + 3] cycloaddition was believed to proceed with sequential nucleophilic 1,4-/1,2-additions.

1. Introduction

Indanone-containing heterocycles are one of the important heterocyclic scaffolds present in various alkaloids and possessing a broad array of biological functions.^1,2 For example, coleophomone D existed in a state of flux between different isomeric forms and possessed antifungal action and the ability to inhibit the serine protease enzyme and heart chymase.³ 4-Azafluorenone and its derivatives exhibit cytotoxic, phosphodiesterase inhibitory, coronary dilating, and calcium modulating activities as well as antimicrobial and antituberculosis agents.⁴ Typically, indenopyridone NSC 314622 serving as a lead compound for the evolution of anticance agents targeting topoisomerase I.⁵ A series of spirocyclic ketones with bi/terphenyls are potential leads for development as new anticancer agents and chemical probes to study signaling networks in neoplastic cells.⁶ Tricyclic 2,3-dicyano indanopyrazinone acts as an efficient nonquinone oxidoreductase (NQO1) substrate and may be a new option for the treatment of NQO1-overexpresssing drug-resistant lung cancer (Figure 1).⁷ On the other hand, some indanone-containing polymers were widely employed in the various materials such as nonlinear optical, organic photovoltaics, and semiconductors.⁸

Some indanone-containing heterocycles with biological property.

Because of the important biological activities they exhibit, significant synthetic effects have been devoted to the synthesis of indanone-containing heterocycles.^9,10 For constructing diverse indanone-containing polycyclic systems, the readily available 1,3-indanedione was regarded as an active substrate because it has three contiguous electrophilic and nucleophilic reactive sites.¹¹⁻¹³ On the other hand, easily prepared 2-arylidene-1,3-indanediones are typical 1,3-dipolarophiles and dienophiles. 2-Arylidene-1,3-indanediones have been widely employed in many Michael addition, condensation reaction, Diels–Alder reaction, cyclization reaction, as well as domino multicomponent reactions.¹⁴⁻¹⁸ Recently, we have found that a domino aza-/oxa-Diels–Alder reaction of α,β-unsaturated N-arylaldimines with 5-arylidene-1,3-dimethylbarbituric acids resulted in polycyclic spiro[pyrido[3′,2′:5,6]pyrano[2,3-d]pyrimidine-7,5′-pyrimidine] derivatives.¹⁹ This unique reaction provided an elegant synthetic protocol for the construction of the polycyclic spiro compounds from the combination of aza-/oxa-Diels–Alder reactions in a one-pot reaction procedure. In order to further demonstrate the potential synthetic values of this reaction for the spiro compounds, we initialed the systematic investigation of various 1-aza-1,4-butadienes and versatile dienophiles in the domino reactions. Herein, we wish to report the domino reaction of α,β-unsaturated aldimines and 2-arylidene-1,3-indanediones for the efficient synthesis of polysubstituted spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridines]. In this domino reaction, 5-arylidene-1,3-indanedione not only acted as an active dienophile, but also played as a useful 1-oxa-1,4-diene to finish the sequential aza-/oxa-Diels–Alder reaction.

2. Results and Discussion

At first, according to our previously established reaction conditions for the reaction of α,β-unsaturated N-arylaldimines with 2-arylidene-N,N′-dimethylbarbituric acids,¹⁹ a mixture of 2-(p-bromobenzylidene)-1.3-indanedione 1a and N-(4-methoxyphenyl)-3-(p-tolyl)prop-2-en-1-imine 2a was stirred in methylene dichloride at room temperature overnight, the expected polycyclic spiro compound 3a was successfully obtained in 31% (Table 1). When the reaction was carried out in refluxing methylene dichloride for eight or 12 h, the yields of 3a increased to 42 and 45%, respectively. The reaction in ethanol did not give the expected product. On the other hand, the reaction in tetrahydrofuran and toluene also resulted in product 3a in lower yields. When acetonitrile was employed as the solvent, the reaction afforded product 3a in 20% yield at room temperature. At the elevated temperature (60 °C), 3a was obtained in 68% yield. When a slight excess of α,β-unsaturated aldimine was used, the yield of 3a increased to 78% yield. The reaction in refluxing acetonitrile decreased the yield of 3a to 73%. Finally, the reaction in a nitrogen atmosphere afforded 3a in a high yield (82%).

Table 1. Optimizing Reaction Conditions^a.

entry	solvent	ratio	T (°C)	time (h)	yield (%)^b
1	DCM	2:1	rt	6	31
2	DCM	2:1	reflux	8	42
3	DCM	2:1	reflux	12	45
4	EtOH	2:1	rt	8
5	EtOH	2:1	reflux	8
6	toluene	2:1	rt	6	10
7	toluene	2:1	reflux	12	21
8	THF	2:1	rt	8	26
9	THF	2:1	reflux	12	26
10	MeCN	2:1	rt	12	20
11	MeCN	2:1	60	6	68
12	MeCN	2:1.1	60	6	78
13	MeCN	2:1.1	reflux	10	73
14	MeCN	2:1.1	60	6	82^c

Open in a new tab

Reaction conditions: α,β-unsaturated N-arylaldimine, 2-arylidene-1,3-indanedione, solvent (10.0 mL).

Isolated yields.

N₂, in Schenk tube.

With the optimized reaction conditions in hand, the scope of the reactions was thoroughly investigated. The results are summarized in Table 2. At first, 2-arylidene-1,3-indanediones with electron-withdrawing fluoro, chloro, bromo, and nitro groups resulted in the spiropolycycles 3a–3p in 65–86% yields. In these reactions, α,β-unsaturated aldimines with electron-donating substituents such as methoxy, methyl, and electron-withdrawing substituents such as chloro, bromo, and nitro groups can be successfully employed in the reaction and showed less effect to the yields of products. Second, 2-benzylidene-1,3-indanediones gave the desired spiropolycycles 3q–3s in moderate yields. Third, 2-(4-methylbenzylidene)-1,3-indanediones afforded the products 3t–3v in lower yields. However, 2-arylidene-1,3-indanediones with m-methyl, m-methoxy, and p-methoxy groups did not result in the expected spiropolycycles. In these reactions, the retro-Knoevenagel condensation reaction of α,β-unsaturated aldimines with 2-arylidene-1,3-indanediones quickly resulted in 2-styrylidene-1,3-indanediones, which can be clearly determined by thin-layer chromatography (TLC) monitoring and were isolated in moderate yields. This cross exchange phenomenon was recently described by Lehn and co-workers as a dynamic covalent metathesis in the C=C/C=N exchange between Knoevenagel compounds and imines involving the formation of a four-membered azetidine ring intermediate.²⁰ The structures of the above-obtained spiropolycycles 3a–3v were fully characterized with infrared (IR), high-resolution mass spectra (HRMS), and ¹H and ¹³C NMR spectroscopy. Through several diastereoisomers might be formed in the reaction, TLC monitoring and ¹H and ¹³C NMR spectra clearly showed that there is only one set of characteristic absorptions for the protons in the molecule, which also indicated only one diastereoisomer existed in the obtained products.

Table 2. Synthesis of Spiropolycycles 3a–3v via the Aza/Oxa-Diels–Alder Reaction^a.

entry	compd	Ar¹	Ar²	Ar³	yield (%)^b
1	3a	p-BrC₆H₄	p-CH₃C₆H₄	p-CH₃OC₆H₄	82
2	3b	p-BrC₆H₄	p-CH₃OC₆H₄	p-CH₃OC₆H₄	86
3	3c	p-BrC₆H₄	p-FC₆H₄	p-CH₃OC₆H₄	71
4	3d	p-BrC₆H₄	p-NO₂C₆H₄	p-CH₃OC₆H₄	65
5	3e	p-BrC₆H₄	Ph	Ph	79
6	3f	p-BrC₆H₄	Ph	p-CH₃OC₆H₄	86
7	3g	p-BrC₆H₄	Ph	p-BrC₆H₄	82
8	3h	p-NO₂C₆H₄	Ph	Ph	75
9	3i	p-NO₂C₆H₄	Ph	p-CH₃OC₆H₄	80
10	3j	p-NO₂C₆H₄	Ph	p-BrC₆H₄	71
11	3k	o-ClC₆H₄	Ph	p-CH₃OC₆H₄	76
12	3l	o-BrC₆H₄	Ph	p-CH₃C₆H₄	85
13	3m	m-ClC₆H₄	Ph	Ph	73
14	3n	m-ClC₆H₄	Ph	p-CH₃OC₆H₄	69
15	3o	m-ClC₆H₄	Ph	p-BrC₆H₄	78
16	3p	m-FC₆H₄	Ph	Ph	68
17	3q	Ph	Ph	Ph	53
18	3r	Ph	Ph	p-CH₃OC₆H₄	48
19	3s	Ph	Ph	p-BrC₆H₄	67
20	3t	p-CH₃C₆H₄	Ph	Ph	43
21	3u	p-CH₃C₆H₄	Ph	p-CH₃OC₆H₄	37
22	3v	p-CH₃C₆H₄	Ph	p-BrC₆H₄	32

Open in a new tab

Reaction conditions: α,β-unsaturated N-arylaldimine (1.1 mmol), 2-arylidene-1,3-indanedione (2.0 mmol), CH₃CN (10.0 mL), 60 °C, 10 h, N₂, in Schenk tube.

Isolated yields.

The above three-molecular reaction usually afforded only one diastereoisomer, which obviously indicated the reaction proceeding with the one-step Diels–Alder reaction. For determining the relative configuration of the obtained products, the single crystal structures of the compounds 3e (Figure 2), 3g, 3i, 3l, and 3p (Figures s1–s4) were successfully determined by the X-ray diffraction method. It was pleasing to find that the same relative configuration was observed in the five single crystals. From Figure 2, it can be seen that the two aryl groups at 2,4-positions exist on the cis-positions in the newly formed tetrahydropyridyl ring, while the third aryl group in the newly formed pyran ring also stands on the cis-position to that of the other two aryl groups. The dihydropyranyl ring fused to the pyrrolidinyl ring from the endo-direction. Thus, on the basis of ¹H NMR spectra and single crystal structures, it can be concluded that all spiropolycylces 3a–3v have this kind of 5,6,8-cis/cis-configuration. It should be pointed out that this kind of configuration is the same as our previously prepared polycyclic compounds derived from the reaction of α,β-unsaturated N-arylaldimines with 5-arylidene-1,3-dimethylbarbituric acids. This result clearly showed that this domino aza/oxa-Diels–Alder reaction of α,β-unsaturated N-arylaldimines with cyclic dienophiles has the same outcome of stereoselectivity.

Single crystal structure of the compound 3g.

For developing the scope of this reaction, α,β-unsaturated N-benzylaldimines were also employed in the reaction. The reaction of various α,β-unsaturated N-benzylaldimines and 2-arylidene-1,3-indanediones in acetonitrile at room temperature gave the desired spiropolycycles 4a–4r in satisfactory yields. However, the reaction at the elevated temperature resulted in lower yields of products, which might be due to the relative instability of α,β-unsaturated N-benzylaldimines to that of N-arylaldimines. The results are summarized in Table 3. It can be seen that benzylamine and its p-CH₃O, p-CH₃, p-Cl, and p-Br derivatives can be successfully used in the reaction. Additionally, α,β-unsaturated N-butylaldimine also reacted smoothly to give the spirocyclic compounds 4q and 4r in good yields. 2-Arylidene-1,3-indanediones with moderate electron-donating methyl groups and electron-withdrawing halo groups (F, Cl, and Br) can be successfully employed in the reaction. 2-Arylidene-1,3-indanediones with strong electron-donating groups, such as the methoxy group, does not take place because these substituents decrease the electrophilic character of the 2-arylidenedione framework in the polar Diels–Alder reactions.²¹¹H and ¹³C NMR spectra clearly indicated that there is only one diastereoisomer existing in the obtained samples. For example, in the ¹H NMR spectrum of compound 4b, the CH₂ protons of the benzyl group showed two doublets at 3.98 ad 3.85 ppm with the germinal coupling constants J = 14.0 Hz. The five CH units in the middle bicyclic ring of pyrano[2,3-b]pyridine gave two doublets at 5.37 and 4.94 ppm, mixed peaks at 3.74–3.63 ppm, and a singlet at 3.55 ppm. The single crystal structures of the compounds 4f (Figure 3) and 4m (Figure s5) were determined by X-ray diffraction. From the figures, it can be seen that they have the same relative configuration to that of the above-mentioned five compounds, in which the three aryl groups exist on the cis-positions and the fused pyrano[2,3-b]pyridine] stretched to the endo-direction. Therefore, the spiropolycycles 3a–3v and 4a–4r have the same relative configuration and were obviously formed via the same diastereoselective reaction pathway.

Table 3. Synthesis of Spiropolycycles 4a–4r via the Aza/Oxa-Diels–Alder Reaction^a.

entry	compd	Ar¹	Ar²	R	yield (%)^b
1	4a	Ph	Ph	Bn	72
2	4b	Ph	Ph	p-ClC₆H₄CH₂	68
3	4c	p-ClC₆H₄	Ph	Bn	72
4	4d	p-ClC₆H₄	Ph	p-CH₃OC₆H₄CH₂	64
5	4e	p-ClC₆H₄	Ph	p-ClC₆H₄CH₂	80
6	4f	p-ClC₆H₄	Ph	p-BrC₆H₄CH₂	82
7	4g	p-ClC₆H₄	p-ClC₆H₄	Bn	76
8	4h	p-ClC₆H₄	p-CH₃OC₆H₄	Bn	73
9	4i	m-FC₆H₄	Ph	p-CH₃C₆H₄CH₂	67
10	4j	m-FC₆H₄	Ph	p-CH₃OC₆H₄CH₂	64
11	4k	m-FC₆H₄	Ph	p-ClC₆H₄CH₂	63
12	4l	m-FC₆H₄	Ph	p-BrC₆H₄CH₂	73
13	4m	p-BrC₆H₄	Ph	Bn	78
14	4n	p-CH₃C₆H₄	Ph	p-CH₃C₆H₄CH₂	60
15	4o	p-CH₃C₆H₄	Ph	p-ClC₆H₄CH₂	65
16	4p	m-CH₃C₆H₄	Ph	p-ClC₆H₄CH₂	60
17	4q	m-FC₆H₄	Ph	n-C₄H₉	76
18	4r	p-BrC₆H₄	Ph	n-C₄H₉	62

Open in a new tab

Reaction conditions: α,β-unsaturated N-alkylaldimine (2.0 mmol), 2-arylidene-1,3-indanedione (1.1 mmol), CH₃CN (10.0 mL), rt, 16 h, N₂, in Schenk tube.

Isolated yields.

Single crystal structure of the compound 4f.

For explaining the reaction mechanism and stereochemistry, a plausible reaction mechanism was proposed in Scheme 1 on the basis of the previously reported reactions^19,21,22 and the obtained experiments. First, an aza-Diels–Alder reaction between 1,4-aryl-1-aza-1,3-butadiene and one molecule of 2-arylidene-1,3-indanedione according to endo-transition state (A) afford terahydropyridine (B).²² Both the aryl groups exist on the cis-positions in the intermediate (B). Then, an oxa-Diels–Alder reaction of the intermediate (B) with another molecule of 2-arylidene-1,3-indanedione via the endo-transition state (A) gave spiropolycycle 3 or 4, in which the three aryl group exist on cis-positions. In this domino reaction, 1,4-aryl-1-aza-1,3-butadiene successfully acted as an active diene to finish the aza-Diels–Alder reaction, and the initially formed terahydropyridine successfully played as an electron-rich dienophile to finish the oxa-Diels–Alder reaction. On the other hand, 5-arylidene-1,3-indanedione not only acted as an active dienophile, but also played as a useful 1-oxa-1,4-diene to the finish sequential aza-/oxa-Diels–Alder reaction. Therefore, the reactivity matching of the two substrates played a key role for this domino aza-/oxa-Diels–Alder reaction.

In the investigation process of the above domino aza/oxa-Diels–Alder reaction, 2,2′-(arylmethylene)bis(1,3-indenediones), which were the byproduct of the base-catalyzed condensation reaction of aromatic aldehydes with 1,3-indanedione for the preparation of 2-arylidene-1,3-indanediones, reacted with α,β-unsaturated N-alkylaldimines in acetonitrile at room temperature to give 2′,4′-diaryl-6′-(arylamino)dispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraones (Table 4). All reactions proceeded smoothly to give dispiro compounds 5a–5n in very high yields. Because there are three chiral carbon atoms in the dispiro compounds, a couple of diastereoisomers might be formed in the reaction. ¹H NMR spectra clearly indicated that two main diastereoisomers with broad molecular ratios of 85:15 to 45:55 exist in the products. By analysis of the stable conformations of 1,3,5-trisubstituted cyclohexane derivatives, the 1,3,5-cis/cis-diastereoisomer was assigned as the most stable isomer because the three substituents exist in the equatorial positions, and the 1,3,5-trans/cis-diastereoisomer was assigned as a less stable isomer, in which one aryl group and arylamino group stand in equatorial positions and the other group exists in the axial position (Scheme 2). The single crystal structures of the compounds 5g and 5i were successfully determined by X-ray diffraction. It can be seen that compound 5g belongs to the 1,3,5-cis/cis-configuration (Figure 4). Compound 5i has a 1,3,5-trans/cis-configuration and the cyclohexyl ring exists in a twist-boat conformation because the bigger o-bromophenyl group in axial position is unstable (Figure s6).

Table 4. Synthesis of Dispirocyclohexanes 5a–5n via the Domino Cyclization Reaction^a.

entry	compd	Ar¹	Ar²	Ar³	yield (%)^b
1	5a	Ph	Ph	Ph	86 (70:30)
2	5b	p-CH₃C₆H₄	Ph	Ph	89 (45:55)
3	5c	o-FC₆H₄	Ph	Ph	92 (70:30)
4	5d	o-FC₆H₄	Ph	m-ClC₆H₄	90 (75:25)
5	5e	o-ClC₆H₄	Ph	Ph	88 (40:60)
6	5f	o-ClC₆H₄	Ph	m-ClC₆H₄	91 (33:67)
7	5g	o-ClC₆H₄	Ph	p-CH₃OC₆H₄	88 (78:22)
8	5h	p-BrC₆H₄	Ph	Ph	87 (65:35)
9	5i	o-BrC₆H₄	Ph	Ph	90 (35:65)
10	5j	o-BrC₆H₄	Ph	p-CH₃C₆H₄	92 (80:20)
11	5k	o-BrC₆H₄	Ph	p-CH₃OC₆H₄	90 (80:20)
12	5l	o-BrC₆H₄	p-CH₃C₆H₄	p-CH₃OC₆H₄	93 (75:25)
13	5m	o-BrC₆H₄	p-CH₃OC₆H₄	p-CH₃OC₆H₄	88 (85:15)
14	5n	o-BrC₆H₄	p-FC₆H₄	p-CH₃OC₆H₄	85 (85:15)

Open in a new tab

Reaction conditions: α,β-unsaturated N-alkylaldimine (0.5 mmol), 2,2′-(arylmethylene)bis(indene-1,3-dione) (0.5 mmol), CH₃CN (10.0 mL), rt, 4 h, N₂, in Schenk tube.

Isolated yields.

Single crystal structures of compound 5g.

A plausible reaction mechanism is also proposed for the formation of the dispiro compounds (Scheme 3). In polar solvent, 2,2′-(arylmethylene)bis(1,3-indenedione) equilibrates with its dienol tautomer (D) via the keto–enol tautomerization. Second, the Michael addition of enol (D) to α,β-unsaturated N-alkylaldimine resulted in the intermediate (E), which equilibrates with imine (F) via enamino–imine tautomerization. Finally, the intramolecular nucleophilic addition of enol to the imine afforded dispiro compound 5. In the final formation of the cyclohexane ring, the thermodynamically stable conformations were obviously formed as the main diastereoisomers. Here, a formal [3 + 3] cycloaddition reaction was successfully finished by the sequential nucleophilic 1,4-/1,2-additions.

3. Conclusions

In summary, we have investigated the domino reaction of α,β-unsaturated aldimines with 2-arylidene-1,3-indenediones and 2,2′-(arylmethylene)bis(1,3-indenediones) and have provided efficient synthetic protocols for polysubstituted spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridines] and dispiro[indene-2,1′-cyclohexane-3′,2″-indenes]. The reaction has the advantages of using readily available reagents, catalyst-free, mild conditions, molecular diversity, good yields, and high diastereoselectivity. The versatile reactivity of α,β-unsaturated aldimines were sufficiently developed, in which it not only acted as active dienophile to accomplish the aza-Diels–Alder reaction, but also acted as dipolarophiles to finish the nucleophilic 1,2-/1,4-addition reaction. Therefore, this domino reaction might be found potential applications in organic and medicinal chemistry.

4. Experimental Section

4.1. General Information

Unless otherwise noted, all reactants or reagents including dry solvents were obtained from commercial suppliers and used as received. Analytical TLC was carried out using 0.25 mm commercial silica gel plates (Merck silica gel 60 F254). The developed chromatogram was analyzed by a UV lamp (254 nm). ¹H NMR and ¹³C NMR spectra were obtained on a Variance 400 M. Chemical shifts (δ) are expressed in parts per million and are internally referenced. IR spectra were taken on a PerkinElmer spectrum 100 FTIR and are reported in reciprocal centimeters (cm^–1). HRMS were obtained on an AB 5800 MALDI-TOF/TOF and are reported as m/z (relative intensity, TOF). Single crystals were obtained by slowly evaporating the compounds in the mixture of chloroform and ethanol. X-ray crystallographic data were collected using a SMART APEX II X-ray diffractometer. Melting points were measured on a Yanaco micro melting point apparatus and are uncorrected. The starting materials α,β-unsaturated N-aryl or N-alkylaldimines,²³ 2-arylidene-1,3-indanediones,²⁴ and 2,2′-(arylmethylene)bis(1,3-indenediones)²⁵ were prepared according to the literature methods.

4.2. General Procedure for the Synthesis of Polycyclic Compounds 3a–3v

Under a N₂ atmosphere, a mixture of α,β-unsaturated N-arylaldimine (1.1 mmol) and 2-arylidene-1,3-indanedione (2.0 mmol) in dry acetonitrile (10.0 mL) was added in a Schlenk tube. The mixture was stirred at 60 °C for 6 h. The solvent was removed by rotatory evaporation at reduced pressure. The residue was subjected to silicon column chromatography with mixed petroleum ether and ethyl acetate (v/v = 6:1 to 10:1) as an eluant to give a pure product for analysis.

4.3. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(4-bromophenyl)-1′-(4-methoxyphenyl)-4′-(p-tolyl)-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3a)

The product is obtained as a yellow solid, 82%, 0.719 g, mp 161–163 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.51 (d, J = 7.6 Hz, 1H), 7.47–7.31 (m, 9H), 7.11 (t, J = 8.2 Hz, 3H), 7.02 (d, J = 8.4 Hz, 2H), 6.93–6.90 (m, 2H), 6.85 (s, 2H), 6.80–6.76 (m, 3H), 6.68 (d, J = 8.8 Hz, 2H), 5.62 (s, 1H), 5.44 (s, 1H), 3.92 (d, J = 12.4 Hz, 1H), 3.70 (m, 4H, CH), 3.58 (s, 1H), 2.10 (s, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃): δ 201.0, 200.9, 192.4, 175.0, 156.9, 151.5, 145.0, 142.8, 142.1, 141.1, 139.7, 137.5, 137.3, 135.3, 135.0, 134.5, 133.3, 132.3, 131.9, 131.8, 130.9, 130.8, 130.4, 130.2, 129.8, 129.4, 129.4, 128.7, 128.4, 126.1, 123.0, 122.8, 122.7, 122.3, 122.0, 121.3, 121.2, 120.7, 118.4, 113.7, 105.5, 93.8, 62.9, 62.5, 55.1, 45.3, 40.8, 34.9, 20.8; IR (KBr) ν: 3052, 2949, 2833, 1904, 1740, 1701, 1631, 1592, 1504, 1475, 1412, 1364, 1246, 1182, 1070, 1016, 955, 876, 819, 783, 742, 718, 639 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₉H₃₆Br₂NO₅ ([M + H]⁺), 878.0940; found, 878.0951.

4.4. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(4-bromophenyl)-1′,4′-bis(4-methoxyphenyl)-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3b)

The product is obtained as a yellow solid, 86%, 0.751 g, mp 133–135 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.51 (d, J = 7.2 Hz, 1H), 7.48–7.31 (m, 8H), 7.28 (s, 1H), 7.18–7.15 (m, 1H), 7.10 (d, J = 8.8 Hz, 2H), 7.03 (d, J = 8.0 Hz, 2H), 6.91 (d, J = 8.4 Hz, 1H), 6.86–6.84 (m, 3H), 6.77 (d, J = 8.4 Hz, 1H), 6.69–6.66 (m, 3H), 6.54–6.51 (m, 1H), 5.62 (d, J = 2.0 Hz, 1H), 5.44 (s, 1H), 3.90 (d, J = 14.4 Hz, 1H), 3.70 (s, 3H), 3.66 (d, J = 13.2 Hz, 1H), 3.63 (s, 3H), 3.59 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 200.8, 200.7, 192.3, 174.9, 163.2, 160.8, 157.0, 142.6, 141.8, 141.0, 139.5, 137.2, 135.6, 135.3, 134.3, 133.7, 133.6, 133.3, 132.0, 131.9, 131.4, 131.3, 131.0, 130.9, 130.8, 130.5, 130.3, 129.8, 129.4, 128.3, 127.9, 127.8, 122.4, 122.2, 122.1, 121.4, 121.3, 120.9, 118.5, 115.9, 115.8, 115.7, 115.6, 114.4, 113.7, 105.3, 93.7, 62.8, 62.4, 55.1, 44.9, 40.6, 35.0; IR (KBr) ν: 3070, 2918, 2847, 1891, 1741, 1700, 1627, 1596, 1510, 1476, 1414, 1369, 1250, 1183, 1075, 1024, 953, 822, 743 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₉H₃₆Br₂NO₆ ([M + H]⁺), 894.0889; found, 894.0893.

4.5. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(4-bromophenyl)-4′-(4-fluorophenyl)-1′-(4-methoxyphenyl)-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3c)

The product is obtained as a yellow solid, 71%, 0.626 g, mp 114–116 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.52–7.32 (m, 9H), 7.25–7.23 (m, 1H), 7.10 (d, J = 8.8 Hz, 2H), 7.02 (d, J = 8.4 Hz, 2H), 6.94–6.91 (m, 2H), 6.87–6.82 (m, 3H), 6.78–6.67 (m, 5H), 5.63 (d, J = 1.6 Hz, 1H), 5.44 (s, 1H), 3.92 (d, J = 12.8 Hz, 1H), 3.73–3.70 (m, 4H), 3.55 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 201.1, 201.0, 192.4, 175.0, 158.9, 156.9, 142.8, 142.1, 141.1, 139.7, 137.3, 135.4, 135.1, 134.5, 133.3, 133.1, 131.9, 131.8, 130.9, 130.9, 130.8, 130.4, 130.3, 129.4, 128.3, 127.3, 127.2, 122.3, 122.0, 121.3, 121.2, 120.8, 118.4, 114.8, 113.7, 113.5, 105.5, 93.8, 62.9, 62.4, 55.1, 55.0, 44.9, 40.9, 34.8; IR (KBr) ν: 3064, 2947, 2837, 1895, 1740, 1701, 1631, 1594, 1504, 1413, 1366, 1240, 1189, 1073, 1008, 954, 876, 825, 743, 636 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₈H₃₃Br₂FNO₅ ([M + H]⁺), 882.0689; found, 882.0693.

4.6. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(4-bromophenyl)-1′-(4-methoxyphenyl)-4′-(4-nitrophenyl)-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3d)

The product is obtained as a yellow solid, 65%, 0.590 g, mp 148–150 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.57–7.30 (m, 12H), 7.27 (s, 1H), 7.17 (t, J = 7.8 Hz, 1H), 7.09 (d, J = 8.8 Hz, 2H), 7.03 (d, J = 8.4 Hz, 2H), 6.91–6.88 (m, 1H), 6.84–6.77 (m, 2H), 6.73–6.67 (m, 3H), 5.65 (d, J = 2.0 Hz, 1H), 5.40 (s, 1H), 4.70 (d, J = 12.4 Hz, 1H), 4.07 (d, J = 13.2 Hz, 1H), 2.70 (s, 3H), 3.61 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 200.9, 199.7, 192.6, 174.5, 157.1, 152.0, 142.7, 141.7, 140.5, 139.4, 137.2, 135.7, 135.4, 133.9, 133.3, 132.1, 131.9, 131.9, 130.9, 130.9, 130.6, 130.2, 130.2, 129.4, 128.8, 128.5, 128.4, 125.2, 122.8, 122.0, 121.5, 121.3, 121.0, 118.4, 113.8, 105.7, 93.1, 63.3, 62.7, 55.2, 40.7, 38.8, 35.4; IR (KBr) ν: 3073, 2919, 2850, 1889, 1740, 1699, 1631, 1595, 1522, 1478, 1415, 1359, 1285, 1244, 1193, 1073, 1017, 956, 821, 754, 705 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₈H₃₃Br₂N₂O₇ ([M + H]⁺), 909.0634; found, 909.0633.

4.7. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(4-bromophenyl)-1′,4′-diphenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3e)

The product is obtained as a yellow solid, 79%, 0.657 g, mp 134–136 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.51–7.49 (m, 1H), 7.47–7.31 (m, 9H), 7.26–7.24 (m, 1H), 7.17–7.13 (m, 5H), 7.05–6.99 (m, 5H), 6.94–6.92 (m, 2H), 6.83–6.81 (m, 3H), 5.74 (d, J = 2.4 Hz, 1H), 5.54 (s, 1H), 3.99–3.96 (m, 1H), 3.72 (d, J = 13.2 Hz, 1H), 3.60 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 200.9, 200.7, 192.3, 174.9, 146.9, 142.7, 142.0, 141.0, 137.2, 135.4, 135.3, 135.1, 134.4, 133.3, 132.1, 132.0, 131.8, 131.0, 130.9, 130.7, 130.5, 130.3, 129.4, 128.9, 128.6, 128.0, 127.1, 126.2, 125.3, 122.3, 122.1, 121.3, 121.2, 120.8, 118.5, 105.5, 93.6, 62.8, 61.9, 45.8, 40.5, 35.0; IR (KBr) ν: 3034, 1742, 1701, 1632, 1593, 1487, 1415, 1370, 1249, 1193, 1073, 1009, 955, 878, 821, 761, 707, 658 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₇H₃₂Br₂NO₄ ([M + H]⁺), 832.0698; found, 832.0683.

4.8. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(4-bromophenyl)-1′-(4-methoxyphenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3f)

The product is obtained as a yellow solid, 86%, 0.741 g, mp 134–136 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.50 (d, J = 7.2 Hz, 1H), 7.47–7.40 (m, 6H), 7.38–7.33 (m, 2H), 7.30 (d, J = 10.8 Hz, 1H), 7.26–7.25 (m, 1H), 7.15–7.10 (m, 3H), 7.04–6.99 (m, 4H), 6.92 (d, J = 8.0 Hz, 2H), 6.86 (s, 2H), 6.78 (d, J = 8.4 Hz, 1H), 6.68 (d, J = 8.8 Hz, 2H), 5.64 (d, J = 2.0 Hz, 1H), 5.46 (s, 1H), 3.95 (d, J = 12.8 Hz, 1H), 3.73–3.70 (m, 4H), 3.59 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 1200.9, 200.8, 192.3, 175.0, 157.0, 142.7, 142.0, 141.0, 139.7, 137.3, 135.4, 135.4, 135.0, 134.4, 133.3, 132.0, 131.9, 131.8, 131.0, 130.9, 130.9, 130.4, 130.3, 129.4, 128.9, 128.6, 128.3, 128.0, 126.2, 122.3, 122.0, 121.3, 121.2, 120.8, 118.4, 113.7, 105.5, 93.8, 62.8, 62.3, 55.1, 45.8, 40.6, 35.0; IR (KBr) ν: 3034, 2955, 2834, 1741, 1700, 1631, 1593, 1506, 1480, 1416, 1372, 1246, 1191, 1074, 1010, 954, 878, 821, 767, 702, 654 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₈H₃₄Br₂NO₅ ([M + H]⁺), 862.0804; found, 862.0803.

4.9. (2′S,4′R,4a′S,5′S,11a′S)-1′,2′,5′-Tris(4-bromophenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3g)

The product is obtained as a yellow solid, 82%, 748 g, mp 132–134 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.51–7.49 (m, 1H), 7.47–7.42 (m, 5H), 7.41–7.32 (m, 3H), 7.29 (d, J = 8.4 Hz, 2H), 7.25–7.22 (m, 2H), 7.15–7.11 (m, 1H), 7.04–6.99 (m, 6H), 6.97–6.86 (m, 3H), 6.81 (d, J = 8.4 Hz, 2H), 5.66 (d, J = 2.4 Hz, 1H), 5.46 (s, 1H), 3.96–3.93 (m, 1H), 3.69 (d, J = 12.8 Hz, 1H), 3.60 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 200.7, 200.6, 192.2, 174.6, 146.1, 142.6, 141.9, 141.0, 137.1, 135.5, 135.2, 135.1, 134.0, 133.1, 132.0, 131.9, 131.8, 131.3, 130.9, 130.7, 130.6, 130.4, 129.4, 128.9, 128.6, 128.6, 128.1, 126.2, 122.4, 122.1, 121.6, 121.3, 120.9, 118.7, 118.4, 105.6, 93.2, 62.6, 61.8, 45.7, 40.5, 34.9; IR (KBr) ν: 3033, 1896, 1741, 1700, 1633, 1592, 1485, 1413, 1371, 1245, 1191, 1073, 1008, 955, 878, 822, 764, 709, 645 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₇H₃₁Br₃NO₄ ([M + H]⁺), 911.9783; found, 911.9810.

4.10. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(4-nitrophenyl)-1′,4′-diphenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3h)

The product is obtained as a yellow solid, 75%, 574 g, mp 147–149 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.21 (d, J = 8.8 Hz, 2H), 7.70–7.68 (m, 1H), 7.60–7.57 (m, 1H), 7.52–7.34 (m, 10H), 7.27 (d, J = 8.8 Hz, 1H), 7.19–7.14 (m, 7H), 7.05–7.02 (m, 3H), 6.97–6.94 (m, 1H), 5.73–5.72 (m, 2H), 4.03 (d, J = 12.8 Hz, 1H), 3.79 (d, J = 12.8 Hz, 1H), 3.75 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 200.3, 200.3, 192.1, 175.0, 150.3, 147.1, 146.8, 146.4, 142.8, 142.4, 140.8, 136.9, 135.8, 135.5, 134.7, 133.0, 132.2, 132.1, 130.6, 130.2, 130.1, 129.1, 128.9, 128.8, 128.6, 128.4, 126.9, 126.0, 125.8, 124.1, 122.8, 122.7, 122.5, 122.2, 121.5, 118.7, 104.8, 93.2, 62.5, 62.0, 45.8, 40.5, 35.5; IR (KBr) ν: 3070, 2948, 2854, 1946, 1740, 1700, 1635, 1595, 1521, 1418, 1345, 1285, 1245, 1195, 1115, 1073, 1007, 957, 855, 759, 703 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₇H₃₂N₃O₈ ([M + H]⁺), 766.2189; found, 766.2196.

4.11. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Methoxyphenyl)-2′,5′-bis(4-nitrophenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3i)

The product is obtained as a yellow solid, 80%, 0.637 g, mp 149–151 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.20 (d, J = 8.4 Hz, 2H), 7.70–7.67 (m, 1H), 7.62–7.59 (m, 1H), 7.52–7.31 (m, 11H), 7.22–7.11 (m, 5H), 7.06–7.02 (m, 2H), 6.95 (s, 1H), 6.68 (d, J = 8.8 Hz, 2H), 5.64–5.63 (m, 2H), 4.01 (d, J = 12.4 Hz, 1H), 3.78 (d, J = 12.8 Hz, 1H), 3.74 (s, 1H), 3.66 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 200.4, 200.3, 192.1, 175.1, 157.3, 150.3, 147.1, 146.7, 142.8, 142.4, 140.8, 139.1, 137.0, 135.8, 135.5, 134.8, 133.1, 132.2, 132.1, 130.6, 130.3, 130.2, 129.1, 128.8, 128.6, 128.4, 128.2, 126.0, 124.1, 122.8, 122.7, 122.5, 122.2, 121.5, 118.7, 114.0, 104.8, 93.4, 62.6, 62.4, 55.2, 45.9, 40.5, 35.5; IR (KBr) ν: 3071, 2944, 2835, 1741, 1702, 1635, 1596, 1517, 1461, 1420, 1346, 1289, 1243, 1192, 1109, 1073, 1006, 956, 846, 756, 701, 657 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₈H₃₄N₃O₉ ([M + H]⁺), 796.2295; found, 796.2287.

4.12. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Bromophenyl)-2′,5′-bis(4-nitrophenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3j)

The product is obtained as a yellow solid, 71%, 0.599 g, mp 151–153 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.21 (d, J = 8.4 Hz, 2H), 7.73–7.70 (m, 1H), 7.64–7.62 (m, 1H), 7.52–7.40 (m, 7H), 7.35–7.28 (m, 5H), 7.24 (s, 1H), 7.19–713 (m, 3H), 7.05–7.03 (m, 4H), 6.92 (s, 1H), 5.65 (s, 2H), 4.01 (d, J = 13.2 Hz, 1H), 3.78–3.74 (m, 2H); ¹³C NMR (100 MHz, CDCl₃): δ 200.2, 200.1, 192.0, 174.7, 150.1, 147.1, 146.9, 145.6, 142.4, 142.3, 140.8, 136.8, 135.9, 135.6, 134.5, 132.9, 132.3, 132.1, 130.7, 130.2, 130.0, 129.2, 128.8, 128.6, 128.5, 128.4, 125.9, 124.1, 123.1, 122.9, 122.5, 122.2, 121.6, 119.4, 118.7, 104.9, 92.8, 62.4, 61.8, 45.8, 40.4, 35.4; IR (KBr) ν: 3071, 2955, 1741, 1702, 1635, 1595, 1520, 1483, 1417, 1347, 1286, 1246, 1192, 1072, 1004, 952, 848, 803, 763, 704 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₇H₃₁BrN₃O₈ ([M + H]⁺), 844.1295; found, 844.1307.

4.13. (2′R,4′R,4a′R,5′R,11a′S)-2′,5′-Bis(2-chlorophenyl)-1′-(4-methoxyphenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3k)

The product is obtained as a yellow solid, 76%, 0.588 g, mp 154–156 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.65 (d, J = 7.1 Hz, 1H), 7.48–7.35 (m, 9H), 7.19–6.93 (m, 10H), 6.85 (s, 1H), 6.66–6.62 (m, 4H), 6.08 (s, 1H), 5.69 (s, 1H), 4.16 (d, J = 12.8 Hz, 1H), 3.83 (d, J = 12.8 Hz, 2H), 3.67 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 202.1, 198.3, 191.9, 175.8, 157.0, 143.4, 141.2, 140.0, 139.3, 137.3, 135.1, 134.9, 134.6, 133.9, 133.6, 133.4, 133.0, 132.5, 132.0, 131.4, 130.5, 130.4, 130.0, 129.4, 128.7, 128.3, 128.1, 128.0, 127.9, 127.8, 126.6, 126.1, 122.6, 122.0, 121.3, 118.5, 113.7, 105.5, 94.6, 62.0, 58.6, 55.2, 46.8, 37.7, 33.6; IR (KBr) ν: 3061, 2920, 1897, 1743, 1702, 1632, 1590, 1510, 1461, 1419, 1371, 1241, 1192, 1072, 1010, 951, 871, 823, 755, 619 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₈H₃₄Cl₂NO₅ ([M + H]⁺), 774.1814; found, 774.1846.

4.14. (2′R,4′R,4a′R,5′R,11a′S)-2′,5′-Bis(2-bromophenyl)-4′-phenyl-1′-(p-tolyl)-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3l)

The product is obtained as a yellow solid, 85%, 0.721 g, mp 159–161 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.67 (d, J = 8.0 Hz, 1H), 7.60 (d, J = 8.5 Hz, 1H), 7.48–7.35 (m, 8H), 7.12–6.78 (m, 13H), 6.65 (t, J = 8.1 Hz, 1H), 6.55–6.51 (m, 1H), 6.07 (s, 1H), 5.76 (s, 1H), 4.17 (d, J = 12.5 Hz, 1H), 3.86–3.81 (m, 2H), 2.17 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 202.2, 198.0, 191.8, 175.7, 144.5, 143.4, 141.3, 140.9, 137.3, 135.1, 134.9, 134.6, 134.5, 134.0, 133.4, 133.0, 132.6, 132.0, 131.6, 130.4, 130.3, 129.2, 128.9, 128.7, 128.4, 127.9, 127.8, 127.2, 127.0, 126.7, 124.6, 124.3, 122.6, 122.1, 121.3, 118.4, 110.0, 105.7, 94.6, 61.9, 61.2, 46.9, 37.7, 35.9, 20.9; IR (KBr) ν: 3035, 2913, 2836, 2332, 1876, 1700, 1630, 1593, 1507, 1459, 1418, 1367, 1241, 1185, 1030, 958, 874, 830, 763, 702, 636 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₈H₃₄Br₂NO₄ ([M + H]⁺), 848.0834; found, 848.0863.

4.15. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(3-chlorophenyl)-1′,4′-diphenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3m)

The product is obtained as a yellow solid, 73%, 0.543 g, mp 163–165 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.58–7.32 (m, 9H), 7.18 (t, J = 4.2 Hz, 5H), 7.12 (s, 1H), 7.05–7.01 (m, 4H), 6.96–6.93 (m, 2H), 6.83 (dd, J = 13.3, 7.0 Hz, 2H), 6.74–6.58 (m, 3H), 5.76–5.74 (m, 1H), 5.54, 5.51 (s, 1H), 4.08–4.01 (m, 1H), 3.76–3.72 (m, 1H), 3.63 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 200.8, 200.7, 200.6, 192.4, 175.0, 147.0, 146.7, 145.0, 145.0, 142.8, 142.7, 141.1, 141.0, 137.5, 137.4, 137.3, 135.5, 135.4, 135.4, 135.3, 135.1, 135.0, 134.7, 133.9, 133.3, 133.1, 132.2, 132.2, 132.1, 132.0, 130.4, 130.1, 129.2, 129.1, 128.9, 128.8, 128.7, 128.5, 128.1, 127.9, 127.8, 127.8, 127.6, 127.5, 127.4, 127.3, 127.3, 127.2, 127.1, 126.4, 126.0, 125.9, 125.5, 125.3, 122.4, 122.3, 122.1, 122.0, 121.3, 118.6, 105.3, 93.6, 93.5, 62.8, 62.8, 62.3, 62.2, 45.6, 40.6, 40.5, 35.3, 35.2; IR (KBr) ν: 3062, 2923, 2853, 1954, 1740, 1700, 1632, 1591, 1484, 1465, 1420, 1367, 1246, 1196, 1078, 1004, 954, 877, 757, 700 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₇H₃₂Cl₂NO₄ ([M + H]⁺), 744.1708; found, 744.1709.

4.16. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(3-chlorophenyl)-1′-(4-methoxyphenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3n)

The product is obtained as a yellow solid, 69%, 0.534 g, mp 168–170 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.57 (d, J = 7.8 Hz, 1H), 7.47–7.28 (m, 9H), 7.14 (dd, J = 16.6, 8.4 Hz, 4H), 7.05–6.89 (m, 6H), 6.78 (d, J = 7.8 Hz, 1H), 6.79–6.66 (m, 5H), 5.65 (s, 1H), 5.47, 5.43 (s, 1H), 4.06–3.98 (m, 1H), 3.74 (s, 1H), 3.70 (d, J = 2.9 Hz, 3H), 3.62 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 200.8, 200.8, 200.7, 200.7, 192.4, 175.1, 157.1, 157.0, 145.1, 145.0, 142.8, 142.7, 141.1, 141.0, 139.7, 139.5, 137.5, 137.4, 137.3, 135.5, 135.5, 135.3, 135.1, 135.0, 134.6, 133.9, 133.3, 133.0, 132.2, 132.1, 132.0, 130.4, 130.1, 129.4, 129.3, 129.1, 128.9, 128.8, 128.7, 128.7, 128.5, 128.4, 128.0, 127.9, 127.8, 127.8, 127.5, 127.2, 127.2, 126.4, 126.0, 126.0, 122.4, 122.3, 122.0, 121.3, 118.6, 113.8, 113.8, 105.3, 93.8, 93.7, 62.9, 62.9, 62.7, 62.7, 55.2, 45.6, 40.6, 40.6, 35.3, 35.2; IR (KBr) ν: 3064, 2950, 2838, 1740, 1701, 1630, 1591, 1507, 1466, 1421, 1365, 1244, 1079, 1026, 953, 877, 833, 776, 748, 701 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₈H₃₄Cl₂NO₅ ([M + H]⁺), 774.1814; found, 774.1790.

4.17. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Bromophenyl)-2′,5′-bis(3-chlorophenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3o)

The product is obtained as a yellow solid, 78%, 0.688 g, mp 130–132 °C; ¹H NMR (400 MHz, CDCl₃): δ ¹H NMR (400 MHz, CDCl₃): δ 7.56 (d, J = 7.6 Hz, 1H), 7.49–7.35 (m, 7H), 7.32–7.28 (m, 3H), 7.24 (d, J = 6.3 Hz, 2H), 7.18–7.14 (m, 1H), 7.11–7.01 (m, 6H), 6.93 (s, 2H), 6.83–6.79 (m, 1H), 6.76–6.67 (m, 2H), 5.68–5.66 (m, 2.0 Hz, 1H), 5.47, 5.44 (s, 1H), 4.05–3.98 (m, 1H), 3.71 (d, J = 13.0 Hz, 1H), 3.62 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 200.6, 200.6, 200.5, 192.3, 174.7, 146.1, 146.0, 144.9, 144.9, 142.8, 142.6, 141.1, 141.0, 137.1, 137.1, 137.1, 137.0, 135.6, 135.4, 135.2, 135.2, 135.2, 135.1, 134.7, 134.7, 134.2, 133.3, 133.2, 132.2, 132.1, 132.1, 131.9, 131.8, 130.5, 130.1, 130.1, 129.3, 129.2, 129.1, 129.0, 129.0, 128.9, 128.8, 128.8, 128.7, 128.7, 128.2, 128.1, 128.1, 127.8, 127.8, 127.5, 127.4, 127.3, 127.2, 126.3, 126.3, 125.9, 125.9, 122.4, 122.4, 122.1, 121.4, 119.0, 118.8, 118.5, 105.4, 105.4, 93.2, 93.2, 62.7, 62.7, 62.1, 62.1, 45.6, 40.5, 40.5, 35.2, 35.2, 30.3, 29.7; IR (KBr) ν: 3065, 2924, 2853, 1740, 1702, 1631, 1590, 1481, 1420, 1364, 1245, 1195, 1075, 1003, 951, 877, 830, 767, 701 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₇H₃₁BrCl₂NO₄ ([M + H]⁺), 822.0814; found, 822.0822.

4.18. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(3-fluorophenyl)-1′,4′-diphenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3p)

The product is obtained as a yellow solid, 68%, 0.484 g, mp 171–173 °C; ¹H NMR (400 MHz, CDCl₃): δ ¹H NMR (400 MHz, CDCl₃): δ 7.56–7.29 (m, 10H), 7.17 (s, 5H), 7.01–6.95 (m, 6H), 6.87 (d, J = 9.2 Hz, 1H), 6.78–6.66 (m, 3H), 6.40–6.39 (m, 1H), 5.77 (s, 1H), 5.59, 5.53 (s, 1H), 4.05 (d, J = 11.5 Hz, 1H), 3.74 (d, J = 12.5 Hz, 1H), 3.65 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 200.9, 200.9, 200.7, 200.7, 192.5, 175.0, 174.9, 164.3, 161.8, 147.1, 146.9, 145.6, 145.5, 142.8, 141.1, 138.1, 137.8, 137.3, 137.3, 135.4, 135.3, 135.1, 135.0, 133.3, 132.2, 132.1, 132.0, 132.0, 130.4, 130.3, 130.3, 129.4, 129.4, 129.1, 129.0, 128.9, 128.9, 128.7, 128.7, 128.7, 128.6, 128.0, 127.1, 126.4, 126.4, 125.4, 125.3, 125.1, 125.1, 124.9, 123.4, 123.3, 122.4, 122.3, 122.1, 122.0, 121.3, 118.6, 118.6, 116.6, 116.4, 116.2, 116.0, 114.9, 114.8, 114.7, 114.3, 114.1, 113.9, 113.8, 105.5, 105.5, 93.7, 62.8, 62.4, 62.1, 45.7, 45.7, 40.5, 35.3; IR (KBr) ν: 3062, 2907, 1954, 1742, 1701, 1634, 1590, 1475, 1417, 1369, 1245, 1184, 1075, 1007, 959, 874, 765, 701 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₇H₃₂F₂NO₇ ([M + H]⁺), 712.2299; found, 712.2315.

4.19. (2′S,4′R,4a′S,5′S,11a′S)-1′,2′,4′,5′-Tetraphenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3q)

The product is obtained as a yellow solid, 53%, 0.358 g, mp 164–166 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.47 (d, J = 7.2 Hz, 1H), 7.41–7.30 (m, 10H), 7.26–7.23 (m, 1H), 7.18–7.10 (m, 7H), 7.00–6.92 (m, 6H), 6.81–6.76 (m, 1H), 6.68–6.64 (m, 2H), 5.83 (d, J = 2.4 Hz, 1H), 5.57 (s, 1H), 4.09 (d, J = 13.2 Hz, 1H), 3.77 (d, J = 13.2 Hz, 1H), 3.67 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 201.2, 200.9, 192.6, 174.9, 147.3, 142.9, 142.9, 141.2, 137.5, 135.8, 135.3, 135.0, 134.6, 133.5, 132.1, 131.8, 130.1, 129.4, 129.0, 128.7, 128.5, 128.3, 127.8, 127.7, 127.3, 127.2, 126.8, 126.5, 124.9, 122.2, 121.9, 121.1, 118.4, 106.0, 93.9, 63.1, 62.7, 45.8, 40.6, 35.4; IR (KBr) ν: 3030, 2856, 1955, 1741, 1701, 1632, 1590, 1490, 1457, 1414, 1368, 1286, 1240, 1195, 1146, 1072, 1004, 949, 872, 761, 699, 623 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₇H₃₄NO₄ ([M + H]⁺), 676.2488; found, 676.2475.

4.20. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Methoxyphenyl)-2′,4′,5′-triphenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3r)

The product is obtained as a yellow solid, 48%, 0.339 g, mp 153–155 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.47 (d, J = 6.8 Hz, 1H), 7.43–7.29 (m, 10H), 7.26–7.22 (m, 1H), 7.17–7.12 (m, 5H), 7.00–6.94 (m, 4H), 6.90 (d, J = 7.6 Hz, 1H), 6.79–6.75 (m, 1H), 6.71–6.64 (m, 4H), 5.73 (d, J = 2.4 Hz, 1H), 5.50 (s, 1H), 4.06 (d, J = 13.2 Hz, 1H), 3.76 (d, J = 13.2 Hz, 1H), 3.67 (s, 3H), 3.66 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 201.2, 200.9, 192.6, 175.0, 156.7, 143.0, 142.9, 141.2, 140.2, 137.5, 135.8, 135.2, 134.9, 134.6, 133.5, 132.1, 131.8, 130.1, 129.5, 129.2, 128.7, 128.7, 128.5, 128.4, 127.7, 127.7, 127.3, 126.7, 126.5, 122.2, 121.9, 121.1, 118.3, 113.5, 106.0, 94.1, 63.1, 63.1, 55.1, 45.8, 40.6, 35.4; IR (KBr) ν: 3030, 2917, 2837, 1882, 1739, 1700, 1625, 1591, 1504, 1455, 1411, 1367, 1244, 1188, 1073, 1028, 955, 922, 878, 832, 766, 699, 625 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₈H₃₆NO₅ ([M + H]⁺), 706.2593; found, 706.2583.

4.21. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Bromophenyl)-2′,4′,5′-triphenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3s)

The product is obtained as a yellow solid, 67%, 0.505 g, mp 116–118 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.47 (d, J = 7.2 Hz, 1H), 7.43–7.37 (m, 5H), 7.34–7.31 (m, 5H), 7.24–7.22 (m, 2H), 7.17–7.12 (m, 3H), 7.04 (d, J = 8.8 Hz, 2H), 7.00 (t, J = 6.4 Hz, 2H), 6.95–6.88 (m, 4H), 6.82–6.78 (m, 1H), 6.72–6.70 (m, 2H), 5.76 (d, J = 2.0 Hz, 1H), 5.50 (s, 1H), 4.06 (d, J = 12.8 Hz, 1H), 3.75 (d, J = 12.8 Hz, 1H), 3.66 (s, 1H); ¹³C NMR (151 MHz, CDCl₃): δ 201.0, 200.8, 192.5, 174.5, 147.0, 142.9, 141.2, 137.4, 135.6, 135.4, 135.2, 135.1, 134.9, 134.7, 134.1, 133.4, 133.2, 132.1, 131.9, 131.5, 130.2, 129.5, 128.9, 128.8, 128.8, 128.7, 128.6, 128.0, 127.9, 127.7, 127.6, 127.5, 126.9, 126.5, 123.3, 123.3, 122.2, 121.9, 121.2, 118.3, 118.3, 106.1, 93.5, 63.0, 62.5, 45.7, 40.5, 35.4, 29.7; IR (KBr) ν: 3062, 2921, 2852, 1740, 1701, 1630, 1591, 1487, 1458, 1412, 1365, 1245, 1193, 1073, 1002, 952, 877, 824, 763, 704, 629 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₇H₃₃BrNO₄ ([M + H]⁺), 754.1593; found, 754.1573.

4.22. (2′S,4′R,4a′S,5′S,11a′S)-1′,4′-Diphenyl-2′,5′-di-p-tolyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3t)

The product is obtained as a yellow solid, 43%, 0.302 g, mp 172–174 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.45 (d, J = 6.8 Hz, 1H), 7.40–7.29 (m, 7H), 7.23 (d, J = 7.2 Hz, 1H), 7.17–7.09 (m, 7H), 7.04 (d, J = 8.0 Hz, 2H), 6.98–6.91 (m, 4H), 6.78 (t, J = 6.6 Hz, 2H), 6.55 (d, J = 7.2 Hz, 1H), 6.46 (d, J = 7.6 Hz, 1H), 5.82 (d, J = 2.0 Hz, 1H), 5.51 (s, 1H), 4.04 (d, J = 12.8 Hz, 1H), 3.73 (d, J = 13.2 Hz, 1H), 3.61 (s, 1H), 2.33 (s, 3H), 1.86 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 201.3, 201.0, 192.6, 174.7, 147.5, 142.9, 141.2, 140.0, 137.6, 136.8, 136.2, 135.9, 134.8, 134.5, 134.4, 133.5, 132.2, 132.1, 131.7, 130.0, 129.6, 129.4, 129.3, 128.8, 128.6, 128.5, 128.5, 128.2, 127.8, 127.7, 127.6, 127.2, 126.5, 124.7, 122.9, 122.1, 121.9, 121.0, 118.3, 106.3, 94.0, 63.2, 62.3, 45.8, 40.5, 35.1, 21.0, 20.7; IR (KBr) ν: 3031, 2856, 1740, 1701, 1632, 1591, 1499, 1459, 1416, 1368, 1247, 1195, 1073, 1007, 954, 876, 808, 757, 704, 603 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₉H₃₈NO₄ ([M + H]⁺), 704.2801; found, 704.2818.

4.23. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Methoxyphenyl)-4′-phenyl-2′,5′-di-p-tolyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3u)

The product is obtained as a yellow solid, 37%, 271 g, mp 128–130 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.47 (d, J = 7.2 Hz, 1H), 7.42–7.27 (m, 8H), 7.14–7.09 (m, 5H), 7.05–7.03 (m, 2H), 6.99–6.97 (m, 2H), 6.95–6.92 (m, 1H), 6.82–6.76 (m, 2H), 6.66 (d, J = 9.2 Hz, 1H), 6.55 (d, J = 7.2 Hz, 1H), 6.48 (d, J = 8.0 Hz, 1H), 5.72 (d, J = 2.4 Hz, 1H), 5.45 (s, 1H), 4.02 (d, J = 12.0 Hz, 1H), 3.73 (d, J = 12.4 Hz, 1H), 3.68 (s, 3H), 3.61 (s, 1H), 2.33 (s, 3H), 1.88 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 201.3, 201.0, 192.6, 174.8, 156.6, 143.0, 141.2, 140.3, 140.0, 137.6, 136.7, 136.2, 135.9, 134.8, 134.5, 133.5, 132.2, 132.1, 131.7, 130.0, 129.4, 129.3, 129.0, 128.6, 128.5, 128.4, 127.8, 127.6, 127.6, 126.5, 122.1, 121.9, 121.0, 118.3, 113.4, 106.2, 94.2, 63.2, 62.7, 55.1, 45.8, 40.6, 35.1, 21.0, 20.7; IR (KBr) ν: 3033, 2921, 2850, 1741, 1701, 1631, 1593, 1509, 1461, 1419, 1370, 1245, 1192, 1075, 1031, 955, 878, 817, 765, 709, 649, 606 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₅₀H₄₀NO₅ ([M + H]⁺), 734.2906; found, 734.2922.

4.24. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Bromophenyl)-4′-phenyl-2′,5′-di-p-tolyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3v)

The product is obtained as a yellow solid, 32%, 0.250 g, mp 149–151 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.47 (d, J = 7.2 Hz, 1H), 7.41–7.34 (m, 6H), 7.33–7.28 (m, 3H), 7.24–7.21 (m, 2H), 7.12 (d, J = 7.6 Hz, 2H), 7.04 (d, J = 8.4 Hz, 4H), 7.00–6.98 (m, 2H), 6.93–6.91 (m, 1H), 6.80–6.75 (m, 2H), 6.58 (d, J = 8.0 Hz, 1H), 6.50 (d, J = 8.0 Hz, 1H), 5.74 (d, J = 2.0 Hz, 1H), 5.45 (s, 1H), 4.01 (d, J = 12.4 Hz, 1H), 3.71 (d, J = 12.4 Hz, 1H), 3.61 (s, 1H), 2.34 (s, 3H), 1.90 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 201.1, 200.9, 192.5, 174.4, 146.7, 142.9, 141.2, 139.9, 137.4, 137.1, 136.3, 135.6, 134.9, 134.6, 133.4, 132.1, 131.8, 131.4, 130.1, 129.4, 129.3, 128.8, 128.7, 128.7, 128.5, 128.0, 127.7, 127.5, 126.5, 122.2, 121.9, 121.1, 118.2, 118.1, 109.9, 106.3, 93.6, 63.0, 62.2, 45.7, 40.5, 35.0, 29.6, 21.0, 20.7; IR (KBr) ν: 3029, 2920, 2858, 1741, 1700, 1634, 1592, 1485, 1415, 1368, 1246, 1191, 1072, 1008, 957, 878, 812, 763, 708, cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₉H₃₇BrNO₄ ([M + H]⁺), 782.1906; found, 782.1910.

4.25. 2-(3-(4-Methoxyphenyl)allylidene)-1H-indene-1,3(2H)-dione

The product is obtained as a yellow solid, 34%, mp 212–214 °C; ¹H NMR (400 MHz, CDCl₃): δ 8.37–8.30 (m, 1H), 7.96–7.94 (m, 2H), 7.80–7.76 (m, 2H), 7.65–7.62 (m, 3H), 7.31 (d, J = 15.4 Hz, 1H), 6.95 (d, J = 8.7 Hz, 2H), 3.87 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 190.74, 190.30, 162.14, 151.45, 145.39, 142.07, 140.76, 134.89, 134.76, 130.68, 128.47, 126.65, 122.94, 122.76, 121.68, 114.57, 55.46; IR (KBr) ν: 3042, 2990, 2845, 2718, 2563, 2031, 1858, 1747, 1679, 1578, 1508, 1461, 1367, 1303, 1257, 1214, 1163, 1022, 986, 864, 818, 733, 698, 601 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₁₉H₁₅O₃ ([M + H]⁺), 291.1021; found, 291.1002.

4.26. General Procedure for the Synthesis of Polycyclic Compounds 4a–4r

Under a N₂ atmosphere, a mixture of α,β-unsaturated N-arylaldimine (1.1 mmol) and 2-arylidene-1,3-indanedione (2.0 mmol) in dry acetonitrile (10.0 mL) was added in a Schlenk tube. The mixture was stirred at room temperature for 24 h. The solvent was removed by rotatory evaporation at reduced pressure. The residue was subjected to silicon column chromatography with mixed petroleum ether and ethyl acetate (v/v = 8:1 to 12:1) as an eluant to give a pure product for analysis.

4.27. (2′S,4′R,4a′S,5′S,11a′S)-1′-Benzyl-2′,4′,5′-triphenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4a)

The product is obtained as a yellow solid, 72%, 0.497 g, mp 158–160 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.50–7.45 (m, 2H), 7.43–7.32 (m, 9H), 7.27 (s, 1H), 7.25–7.19 (m, 3H), 7.14–7.06 (m, 4H), 6.96–6.87 (m, 9H), 5.45 (d, J = 2.0 Hz, 1H), 4.95 (s, 1H), 4.01–3.89 (m, 2H), 3.76–3.64 (m, 2H), 3.54 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 201.3, 192.6, 174.7, 143.0, 142.9, 141.2, 137.8, 137.0, 135.8, 135.7, 135.0, 134.7, 133.6, 132.0, 130.1, 128.7, 128.7, 128.6, 128.6, 128.5, 128.5, 128.4, 128.2, 127.7, 127.3, 127.2, 126.7, 126.6, 122.2, 121.9, 121.1, 118.2, 106.6, 90.1, 64.9, 63.5, 52.7, 45.7, 39.6, 35.4; IR (KBr) ν: 3030, 2920, 2859, 1958, 1883, 1816, 1738, 1701, 1632, 1593, 1492, 1457, 1409, 1385, 1361, 1249, 1194, 1071, 1022, 955, 887, 761, 701, 618 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₈H₃₆NO₄ ([M + H]⁺), 690.2644; found, 690.2652.

4.28. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Chlorobenzyl)-2′,4′,5′-triphenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4b)

The product is obtained as a yellow solid, 68%, 0.492 g, mp 169–171 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.48 (t, J = 8.5 Hz, 2H), 7.42–7.33 (m, 6H), 7.24–7.16 (m, 9H), 7.09 (br s, 1H), 6.96–6.86 (m, 9H), 5.37 (d, J = 2.4 Hz, 1H), 4.94 (d, J = 1.8 Hz, 1H), 3.98 (d, J = 14.0 Hz, 1H), 3.85 (d, J = 14.0 Hz, 1H), 3.74–3.63 (m, 2H), 3.55 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 201.3, 201.1, 192.5, 174.5, 142.9, 142.9, 141.2, 137.7, 135.7, 135.6, 135.5, 135.1, 134.8, 133.5, 132.9, 132.0, 132.0, 130.2, 129.9, 128.7, 128.6, 128.5, 128.5, 128.3, 128.2, 127.8, 127.3, 126.7, 126.6, 122.2, 121.9, 121.2, 118.2, 106.6, 90.0, 64.8, 63.4, 52.2, 45.6, 39.7, 35.4; IR (KBr) ν: 3029, 2944, 2860, 1960, 1822, 1735, 1696, 1629, 1590, 1489, 1458, 1414, 1378, 1276, 1177, 1080, 1016, 945, 895, 821, 764, 703, 659, 621 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₈H₃₅ClNO₄ ([M + H]⁺), 724.2255; found, 724.2266.

4.29. (2′S,4′R,4a′S,5′S,11a′S)-1′-Benzyl-2′,5′-bis(4-chlorophenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4c)

The product is obtained as a yellow solid, 72%, 0.546 g, mp 132–134 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.52–7.41 (m, 6H), 7.38–7.28 (m, 7H), 7.24 (d, J = 6.1 Hz, 1H), 7.16–7.06 (m, 4H), 6.96–6.94 (m, 5H), 6.88–6.84 (m, 3H), 5.36 (s, 1H), 4.93 (s, 1H), 3.97 (d, J = 13.7 Hz, 1H), 3.83 (d, J = 13.7 Hz, 1H), 3.63 (s, 2H), 3.50 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 201.1, 201.0, 192.4, 174.7, 142.8, 141.5, 141.1, 137.5, 136.6, 135.4, 135.3, 135.1, 134.3, 134.0, 133.4, 132.5, 132.1, 131.9, 130.3, 128.8, 128.7, 128.6, 128.6, 128.6, 128.5, 127.9, 127.4, 126.4, 122.4, 122.1, 121.3, 118.4, 106.2, 89.8, 64.1, 63.2, 52.8, 45.7, 39.5, 34.9; IR (KBr) ν: 3032, 2871, 1894, 1700, 1638, 1595, 1488, 1416, 1371, 1250, 1184, 1092, 1017, 948, 893, 822, 766, 707, 612 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₈H₃₄Cl₂NO₄ ([M + H]⁺), 758.1865; found, 758.1878.

4.30. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(4-chlorophenyl)-1′-(4-methoxybenzyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4d)

The product is obtained as a white solid, 64%, 0.504 g, mp 154–156 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.52–7.42 (m, 9H), 7.20 (d, J = 8.0 Hz, 2H), 7.15–7.06 (m, 4H), 7.01–6.95 (m, 5H), 6.89–6.80 (m, 5H), 5.33 (s, 1H), 4.90 (s, 1H), 3.89–3.75 (m, 5H), 3.60 (s, 2H), 3.50 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 201.1, 201.1, 192.4, 174.8, 159.0, 142.8, 141.6, 141.1, 137.5, 135.4, 135.3, 135.1, 134.4, 133.9, 133.5, 132.4, 132.1, 131.9, 130.3, 130.0, 128.8, 128.7, 128.6, 128.5, 128.3, 127.9, 126.4, 122.3, 122.0, 121.3, 118.4, 113.9, 106.1, 89.7, 64.1, 63.3, 55.3, 52.3, 45.6, 39.6, 34.9; IR (KBr) ν: 3039, 2948, 2839, 1903, 1739, 1699, 1630, 1593, 1499, 1463, 1411, 1251, 1188, 1093, 1021, 950, 888, 823, 763, 708, 657, 609 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₉H₃₆Cl₂NO₅ ([M + H]⁺), 788.1971; found, 788.1988.

4.31. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Chlorobenzyl)-2′,5′-bis(4-chlorophenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4e)

The product is obtained as a yellow solid, 80%, 0.634 g, mp 163–165 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.53–7.34 (m, 8H), 7.25–7.22 (m, 4H), 7.16 (d, J = 8.2 Hz, 3H), 7.10–7.06 (m, 2H), 6.96 (d, J = 3.8 Hz, 5H), 6.89–6.85 (m, 3H), 5.29 (s, 1H), 4.92 (s, 1H), 3.98 (d, J = 14.4 Hz, 1H), 3.78 (d, J = 14.0 Hz, 1H), 3.65–3.58 (m, 2H), 3.51 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 201.2, 200.9, 192.3, 174.5, 142.8, 141.4, 141.0, 137.4, 135.5, 135.3, 135.3, 135.2, 135.2, 134.1, 134.1, 133.3, 133.2, 132.7, 132.1, 131.9, 130.4, 129.8, 129.1, 128.8, 128.7, 128.7, 128.6, 128.6, 128.0, 126.3, 122.4, 122.0, 121.4, 118.3, 106.2, 89.8, 64.1, 63.1, 52.3, 45.7, 39.7, 34.9; IR (KBr) ν: 3059, 2912, 2852, 1895, 1816, 1698, 1628, 1591, 1486, 1409, 1249, 1187, 1091, 1014, 949, 892, 817, 765, 710 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₈H₃₃Cl₃NO₄ ([M + H]⁺), 792.1475; found, 792.1501.

4.32. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Bromobenzyl)-2′,5′-bis(4-chlorophenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4f)

The product is obtained as a yellow solid, 82%, 0.685 g, mp 169–171 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.52–7.35 (m, 10H), 7.18–7.09 (m, 6H), 7.09 (s, 1H), 6.96–6.86 (m, 8H), 5.28 (s, 1H), 4.92 (s, 1H), 3.96 (d, J = 14.2 Hz, 1H), 3.76 (d, J = 13.7 Hz, 1H), 3.65–3.58 (m, 2H), 3.51 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 201.2, 200.9, 192.3, 174.5, 142.8, 141.4, 141.0, 137.4, 135.8, 135.5, 135.2, 134.1, 134.0, 133.3, 132.7, 132.1, 131.9, 131.7, 130.4, 130.2, 128.8, 128.7, 128.6, 128.6, 128.0, 126.3, 122.4, 122.1, 121.4, 121.3, 118.3, 106.2, 89.8, 64.1, 63.1, 52.4, 45.7, 39.7, 34.9; IR (KBr) ν: 3054, 2911, 2849, 1896, 1698, 1591, 1483, 1405, 1250, 1186, 1088, 1012, 951, 891, 819, 763, 712 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₈H₃₃BrCl₂NO₄ ([M + H]⁺), 836.0970; found, 836.0982.

4.33. (2′S,4′R,4a′S,5′S,11a′S)-1′-Benzyl-2′,4′,5′-tris(4-chlorophenyl)-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4g)

The product is obtained as a yellow solid, 76%, 0.602 g, mp 164–166 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.53–7.36 (m, 8H), 7.28 (s, 5H), 7.12–7.10 (m, 5H), 6.96 (d, J = 8.1 Hz, 4H), 6.84 (t, J = 8.0 Hz, 3H), 5.35 (s, 1H), 4.90 (s, 1H), 3.95 (d, J = 13.6 Hz, 1H), 3.83 (d, J = 13.6 Hz, 1H), 3.61 (s, 2H), 3.42 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 201.0, 200.8, 192.3, 174.6, 142.7, 141.2, 141.0, 137.4, 136.4, 135.7, 135.5, 134.1, 134.1, 133.8, 133.4, 133.2, 132.6, 132.1, 130.4, 129.1, 129.0, 128.8, 128.7, 128.6, 128.6, 127.8, 127.5, 122.5, 122.2, 121.3, 118.4, 106.0, 89.6, 64.3, 63.1, 52.8, 44.8, 39.5, 34.9; IR (KBr) ν: 3064, 2958, 2850, 1910, 1820, 1698, 1593, 1484, 1411, 1360, 1252, 1195, 1092, 1014, 955, 886, 827, 754, 703, 634 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₈H₃₃Cl₃NO₄ ([M + H]⁺), 792.1475; found, 792.1480.

4.34. (2′S,4′R,4a′S,5′S,11a′S)-1′-Benzyl-2′,5′-bis(4-chlorophenyl)-4′-(4-methoxyphenyl)-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4h)

The product is obtained as a yellow solid, 73%, 0.575 g, mp 131–133 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.54–7.41 (m, 6H), 7.37–7.28 (m, 7H), 7.23 (s, 1H), 7.11–7.05 (m, 3H), 6.95 (s, 3H), 6.87 (d, J = 8.0 Hz, 2H), 6.79 (d, J = 8.0 Hz, 1H), 6.63 (d, J = 9.0 Hz, 1H), 6.48 (d, J = 8.3 Hz, 1H), 5.35 (s, 1H), 4.90 (s, 1H), 3.96 (d, J = 13.5 Hz, 1H), 3.82 (d, J = 13.6 Hz, 1H), 3.59 (m, 5H), 3.50 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 201.4, 201.2, 192.4, 174.7, 158.9, 142.9, 141.5, 141.1, 137.6, 136.6, 135.4, 135.2, 134.4, 133.9, 133.4, 133.0, 132.4, 132.1, 130.3, 128.7, 128.6, 128.6, 128.5, 127.4, 127.3, 122.4, 122.0, 121.2, 118.3, 114.6, 113.5, 106.2, 89.8, 64.2, 63.3, 55.1, 52.8, 44.8, 39.8, 34.7; IR (KBr) ν: 3033, 2943, 2839, 1898, 1699, 1594, 1502, 1407, 1254, 1182, 1093, 1022, 952, 889, 824, 755, 708 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₉H₃₆Cl₂NO₄ ([M + H]⁺), 788.1971; found, 788.1978.

4.35. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(3-fluorophenyl)-1′-(4-methylbenzyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4i)

The product is obtained as a yellow solid, 67%, 0.496 g, mp 155–157 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.49–7.34 (m, 8H), 7.18 (t, J = 8.4 Hz, 3H), 7.13–7.07 (m, 5H), 6.96 (s, 3H), 6.83–6.73 (m, 4H), 6.62 (t, J = 10.6 Hz, 2H), 5.35 (s, 1H), 4.93 (s, 1H), 3.87 (q, J = 13.4, 12.7 Hz, 2H), 3.67–3.60 (m, 2H), 3.51 (s, 1H), 2.32 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 201.0, 192.4, 174.8, 164.0, 161.6, 145.6, 142.8, 141.1, 137.5, 137.2, 135.3, 135.0, 133.5, 132.1, 131.9, 130.3, 130.0, 129.9, 129.2, 128.7, 128.5, 127.9, 126.5, 123.0, 122.0, 121.2, 118.4, 114.4, 114.2, 113.7, 113.5, 106.0, 89.6, 63.2, 52.7, 45.5, 39.4, 35.2, 21.0; IR (KBr) ν: 3037, 2960, 2918, 2854, 1894, 1738, 1698, 1592, 1463, 1415, 1247, 1189, 1146, 1074, 1025, 938, 880, 764, 702, 632 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₉H₃₆F₂NO₄ ([M + H]⁺), 740.2612; found, 740.2620.

4.36. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(3-fluorophenyl)-1′-(4-methoxybenzyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4j)

The product is obtained as a yellow solid, 64%, 0.484 g, mp 129–131 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.49–7.38 (m, 8H), 7.24–7.08 (m, 6H), 6.96 (s, 3H), 6.87–6.74 (m, 6H), 6.62 (d, J = 6.0 Hz, 2H), 5.36 (s, 1H), 4.90 (d, J = 14.9 Hz, 1H), 3.90–3.79 (m, 5H), 3.66–3.60 (m, 2H), 3.52 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 201.0, 192.4, 174.8, 164.0, 161.6, 159.0, 145.6, 145.6, 142.8, 141.1, 137.5, 135.3, 135.0, 133.5, 132.1, 131.9, 130.3, 130.1, 130.0, 129.9, 128.7, 128.6, 127.9, 126.5, 123.0, 123.0, 122.3, 122.0, 121.3, 118.4, 114.4, 114.2, 114.0, 113.7, 113.5, 106.0, 89.6, 63.2, 55.3, 52.4, 45.5, 39.4, 35.2; IR (KBr) ν: 3042, 2947, 2844, 1956, 1882, 1701, 1595, 1502, 1455, 1388, 1249, 1168, 1076, 1024, 941, 878, 761, 701, 638 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₉H₃₆F₂NO₅ ([M + H]⁺), 756.2562; found, 756.2566.

4.37. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Chlorobenzyl)-2′,5′-bis(3-fluorophenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4k)

The product is obtained as a yellow solid, 63%, 0.479 g, mp 163–165 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.53–7.35 (m, 10H), 7.19–7.10 (m, 4H), 7.97–6.86 (m, 6H), 6.75–7.61 (m, 5H), 5.31 (s, 1H), 4.93 (s, 1H), 3.99 (d, J = 13.7 Hz, 1H), 3.82 (d, J = 13.2 Hz, 1H), 3.69 (d, J = 12.8 Hz, 1H), 3.61 (d, J = 13.2 Hz, 1H), 3.53 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 201.1, 200.8, 192.3, 174.6, 164.1, 161.7, 145.5, 145.4, 142.8, 141.0, 138.1, 138.1, 137.4, 135.4, 135.2, 135.1, 133.4, 133.2, 132.2, 131.9, 130.4, 130.1, 130.0, 129.9, 128.8, 128.7, 128.6, 128.0, 126.4, 122.9, 122.8, 122.4, 122.1, 121.4, 118.4, 114.5, 114.2, 113.9, 113.7, 106.0, 89.7, 63.1, 52.3, 45.5, 39.5, 35.2; IR (KBr) ν: 3058, 2947, 2909, 2863, 1959, 1695, 1590, 1482, 1376, 1268, 1178, 1078, 1012, 933, 879, 752, 700 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₈H₃₃ClF₂NO ([M + H]⁺), 760.2066; found, 760.2069.

4.38. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Bromobenzyl)-2′,5′-bis(3-fluorophenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4l)

The product is obtained as a yellow solid, 73%, 0.587 g, mp 170–172 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.53–7.39 (m, 10H), 7.20–7.11 (m, 5H), 7.97–6.86 (m, 6H), 6.75–6.61 (m, 4H), 5.31 (s, 1H), 4.94 (s, 1H), 3.98 (d, J = 14.1 Hz, 1H), 3.81 (d, J = 14.3 Hz, 1H), 3.71–3.60 (m, 2H), 3.53 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 201.0, 200.8, 192.3, 174.6, 164.1, 161.7, 145.5, 145.4, 142.8, 141.0, 138.1, 138.0, 137.4, 135.4, 135.2, 135.1, 133.4, 132.1, 131.9, 131.7, 130.4, 130.3, 130.1, 130.0, 128.8, 128.6, 128.0, 126.4, 122.8, 122.8, 122.4, 122.0, 121.4, 118.3, 114.5, 114.3, 113.9, 113.7, 106.1, 89.7, 63.1, 52.4, 45.5, 39.5, 35.1; IR (KBr) ν: 3056, 2946, 2908, 2862, 1960, 1736, 1696, 1591, 1482, 1378, 1248, 1180, 1072, 1006, 933, 880, 761, 701, 639 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₈H₃₃BrF₂N₅O₆ ([M + H]⁺), 804.1561; found, 804.1556.

4.39. (2′S,4′R,4a′S,5′S,11a′S)-1′-Benzyl-2′,5′-bis(4-bromophenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4m)

The product is obtained as a yellow solid, 78%, 0.661 g, mp 137–139 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.52–7.41 (m, 7H), 7.36 (t, J = 6.6 Hz, 2H), 7.33–7.28 (m, 5H), 7.24 (s, 2H), 7.15–7.05 (m, 5H), 6.96–6.94 (m, 2H), 6.86–6.81 (m, 3H), 5.36 (s, 1H), 4.91 (s, 1H), 3.97 (d, J = 13.7 Hz, 1H), 3.83 (d, J = 13.7 Hz, 1H), 3.62 (s, 2H), 3.48 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 201.1, 201.0, 192.4, 174.7, 142.8, 142.0, 141.1, 137.5, 136.5, 135.4, 135.3, 135.2, 134.9, 133.4, 132.1, 131.9, 131.6, 130.3, 129.1, 128.8, 128.6, 128.5, 127.9, 127.5, 126.4, 122.4, 122.2, 122.1, 121.3, 120.6, 118.4, 106.1, 89.8, 64.2, 63.2, 52.9, 45.7, 39.5, 35.0; IR (KBr) ν: 3032, 2868, 1893, 1826, 1700, 1637, 1595, 1483, 1414, 1371, 1249, 1184, 1074, 1012, 948, 892, 818, 765, 703, 654 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₈H₃₄Br₂NO₄ ([M + H]⁺), 848.0834; found, 848.0844.

4.40. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Methylbenzyl)-4′-phenyl-2′,5′-di-p-tolyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4n)

The product is obtained as a yellow solid, 60%, 0.439 g, mp 150–152 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.49–7.44 (m, 2H), 7.40–7.31 (m, 6H), 7.19 (t, J = 6.9 Hz, 3H), 7.11–7.00 (m, 4H), 6.92 (d, J = 5.6 Hz, 4H), 6.86–6.81 (m, 4H), 6.77 (s, 2H), 5.41 (s, 1H), 4.89 (s, 1H), 3.91–3.82 (m, 2H), 3.68–3.59 (m, 2H), 3.49 (s, 1H), 2.32 (s, 3H), 2.26 (s, 3H), 2.03 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 201.5, 201.3, 192.7, 174.6, 143.0, 141.2, 140.0, 137.9, 137.7, 136.6, 135.9, 135.8, 134.9, 134.6, 134.5, 134.0, 133.7, 132.7, 131.9, 131.9, 130.0, 129.1, 129.0, 128.8, 128.5, 128.4, 127.8, 127.6, 127.2, 126.7, 122.2, 121.9, 121.0, 118.2, 106.9, 90.2, 64.5, 63.6, 52.4, 45.7, 39.4, 35.1, 21.1, 21.0, 20.9; IR (KBr) ν: 3029, 2918, 2862, 1956, 1699, 1646, 1591, 1487, 1372, 1245, 1172, 1092, 1013, 952, 893, 815, 758, 706, 612 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₅₁H₄₂NO₄ ([M + H]⁺), 732.3114; found, 732.3142.

4.41. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Chlorobenzyl)-4′-phenyl-2′,5′-di-p-tolyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4o)

The product is obtained as a yellow solid, 65%, 0.489 g, mp 145–147 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.50–7.31 (m, 8H), 7.26–7.14 (m, 6H), 7.08–7.05 (m, 1H), 6.98–6.93 (m, 4H), 6.84 (d, J = 7.8 Hz, 4H), 6.76 (d, J = 7.7 Hz, 2H), 5.35 (s, 1H), 4.90 (s, 1H), 3.95 (d, J = 14.4 Hz, 1H), 3.84 (d, J = 13.7 Hz, 1H), 3.64 (q, J = 13.2 Hz, 2H), 3.51 (s, 1H), 2.29 (s, 3H), 2.03 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 201.4, 201.3, 192.6, 174.5, 143.0, 141.2, 139.9, 137.9, 137.7, 136.2, 135.9, 135.7, 135.0, 134.7, 133.6, 132.8, 132.4, 131.9, 131.9, 130.1, 130.0, 129.2, 128.7, 128.6, 128.5, 128.4, 127.7, 127.1, 126.6, 122.2, 121.9, 121.1, 118.2, 106.9, 90.1, 64.4, 63.4, 52.0, 45.7, 39.6, 35.0, 21.0, 20.9; IR (KBr) ν: 3027, 2915, 2861, 1952, 1888, 1699, 1637, 1593, 1481, 1412, 1370, 1244, 1175, 1090, 1015, 939, 857, 761, 703 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₅₀H₃₉NO₄ ([M + H]⁺), 752.2568; found, 752.2504.

4.42. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Chlorobenzyl)-4′-phenyl-2′,5′-di-m-tolyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4p)

The product is obtained as a yellow solid, 60%, 0.451 g, mp 140–142 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.48 (t, J = 5.9 Hz, 2H), 7.43–7.35 (m, 6H), 7.26–7.19 (m, 4H), 7.09–7.02 (m, 4H), 6.96 (d, J = 4.0 Hz, 3H), 6.88–6.77 (m, 5H), 6.70 (d, J = 5.9 Hz, 1H), 6.65 (s, 1H), 5.40 (s, 1H), 4.87 (s, 1H), 3.90 (q, J = 15.2, 14.4 Hz, 2H), 3.67–3.60 (m, 2H), 3.50 (s, 1H), 2.18 (s, 3H), 2.06 (d, J = 13.3 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 201.3, 201.2, 192.5, 174.4, 142.9, 138.1, 137.8, 135.7, 135.7, 135.0, 134.7, 133.6, 133.0, 132.0, 132.0, 130.2, 130.1, 128.6, 128.6, 128.5, 128.4, 127.7, 127.6, 127.5, 126.7, 124.6, 121.2, 118.2, 106.8, 89.8, 64.9, 63.4, 52.2, 45.5, 39.4, 35.3, 21.4; IR (KBr) ν: 3066, 2940, 2855, 1949, 1872, 1740, 1702, 1636, 1593, 1486, 1417, 1368, 1247, 1196, 1145, 1073, 1010, 960, 876, 762, 701, 638 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₅₀H₃₉ClNO₄ ([M + H]⁺), 752.2568; found, 752.2588.

4.43. (2′S,4′R,4a′S,5′S,11a′S)-1′-Butyl-2′,5′-bis(3-fluorophenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4q)

The product is obtained as a yellow solid, 76%, 0.526 g, mp 151–153 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.52–7.28 (m, 10H), 7.22 (d, J = 8.3 Hz, 1H), 7.11 (s, 1H), 7.03–6.87 (m, 7H), 6.75–6.68 (m, 1H), 6.62 (t, J = 8.6 Hz, 1H), 5.64 (s, 1H), 4.84 (d, J = 17.9 Hz, 1H), 3.80 (d, J = 13.9 Hz, 1H), 3.61–3.57 (m, 2H), 3.04–2.93 (m, 1H), 2.58 (br s, 1H), 1.50 (s, 1H), 1.30 (s, 1H), 1.15–1.07 (m, 2H), 0.76 (t, J = 7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 201.2, 201.0, 192.5, 175.3, 164.3, 161.8, 145.9, 145.8, 142.8, 141.0, 137.5, 135.4, 135.3, 134.9, 133.5, 132.1, 32.0, 130.3, 130.2, 129.6, 128.8, 128.6, 127.9, 126.5, 123.4, 123.3, 122.3, 122.0, 121.2, 118.5, 114.8, 114.6, 113.9, 113.7, 105.5, 92.0, 63.0, 50.1, 45.4, 40.0, 35.2, 29.1, 20.3, 13.8; IR (KBr) ν: 3068, 2960, 2864, 1956, 1880, 1738, 1698, 1589, 1459, 1411, 1376, 1249, 1196, 1148, 1071, 1014, 936, 877, 768, 704, 630 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₅H₃₆F₂NO₄ ([M + H]⁺), 692.2612; found, 692.2608.

4.44. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(4-bromophenyl)-1′-butyl-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4r)

The product is obtained as a yellow solid, 62%, 0.505 g, mp 134–136 °C; ¹H NMR (400 MHz, CDCl₃): δ 7.51–7.36 (m, 10H), 7.19–7.09 (m, 7H), 6.95 (s, 2H), 6.85 (s, 2H), 5.60 (s, 1H), 4.81 (s, 1H), 3.72 (d, J = 13.0 Hz, 1H), 3.58–3.56 (m, 2H), 2.97–2.90 (m, 1H), 2.54 (br s, 1H), 1.47 (br s, 2H), 1.14–1.06 (m, 2H), 0.77 (t, J = 6.5 Hz, 3H₃); ¹³C NMR (100 MHz, CDCl₃): δ 201.3, 201.1, 192.6, 175.3, 142.7, 142.2, 141.0, 137.5, 135.4, 135.3, 135.1, 134.7, 133.5, 132.1, 132.1, 131.9, 131.8, 131.3, 131.0, 130.3, 130.0, 129.4, 128.8, 128.5, 127.9, 126.4, 123.5, 122.3, 122.1, 121.9, 121.3, 120.8, 118.5, 105.6, 91.9, 63.5, 63.0, 50.1, 45.5, 40.0, 34.9, 29.1, 20.3, 18.4, 13.9.; IR (KBr) ν: 3064, 2951, 2862, 1895, 1700, 1632, 1591, 1478, 1411, 1369, 1250, 1195, 1072, 1009, 955, 888, 816, 761, 706 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₅H₃₈BrNO₄ ([M + H]⁺), 814.0991; found, 814.1009.

4.45. General Procedure for the Synthesis of Dispiro Compounds 5a–5m

A mixture of α,β-unsaturated N-arylaldimine (0.5 mmol) and 2,2′-(arylmethylene)bis(indene-1,3-dione) (0.5 mmol) in dry acetonitrile (10.0 mL) was stirred at room temperature for 10 h. The solvent was removed by rotatory evaporation at reduced pressure. The residue was subjected with silicon column chromatography with mixed petroleum ether and ethyl acetate (v/v = 2:1) as an eluant to give a pure product for analysis.

4.46. 2′,4′-Diphenyl-6′-(phenylamino)dispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraone (5a)

The product is obtained as a yellow solid, 86%, 0.253 g, mp 179–183 °C; ¹H NMR (400 MHz, CDCl₃): δ trans-isomer: 8.11 (d, J = 7.3 Hz, 1H), 7.73 (m, J = 7.2 Hz, 1H), 7.65–7.34 (m, 6H), 7.13–6.86 (m, 7H), 6.79–6.56 (m, 7H), 6.55–6.42 (m, 1H), 4.99–4.94 (m, 2H), 4.31–4.27 (m, 1H), 4.07 (d, J = 12.1 Hz, 1H), 3.47–3.39 (m, 1H), 2.04 (d, J = 13.5 Hz, 1H); cis-isomer: 7.96 (d, J = 7.3 Hz, 1H), 7.65–7.34 (m, 7H), 4.70 (s, 1H), 4.65 (d, J = 11.9 Hz, 1H), 4.20 (d, J = 12.5 Hz, 1H), 3.05 (d, J = 11.5 Hz, 1H), 2.34 (d, J = 13.4 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 203.4, 203.1, 202.7, 202.6, 202.2, 201.5, 201.3, 201.1, 146.1, 144.0, 143.1, 142.8, 142.6, 142.3, 141.6, 141.4, 139.1, 139.0, 135.6, 135.3, 135.1, 135.0, 134.9, 134.8, 134.0, 133.6, 130.9, 129.1, 129.0, 128.7, 128.6, 128.4, 128.0, 128.0, 127.8, 127.6, 127.4, 127.3, 127.0, 126.9, 122.9, 122.7, 122.5, 122.4, 122.3, 122.2, 115.4, 115.2, 114.7, 63.7, 63.3, 62.6, 61.9, 58.1, 56.1, 55.4, 53.7, 53.0, 51.9, 45.6, 43.6, 31.3, 31.2; IR (KBr) ν: 3039, 1704, 1595, 1499, 1446, 1341, 1248, 1155, 1115, 1031, 958, 884, 760 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₀H₃₀NO₄ ([M + H]⁺), 588.2175; found, 588.2177.

4.47. 4′-Phenyl-6′-(phenylamino)-2′-(p-tolyl)dispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraone (5b)

The product is obtained as a yellow solid, 89%, 0.268 g, mp 184–189 °C; ¹H NMR (400 MHz, CDCl₃): δ trans-isomer: 8.10 (d, J = 8.4 Hz, 1H), 7.73 (t, J = 7.0 Hz, 1H), 7.64–7.36 (m, 6H), 7.08–6.88 (m, 7H), 6.66–6.45 (m, 7H), 4.95 (d, J = 16.0 Hz, 2H), 4.27 (d, J = 8.8 Hz, 1H), 4.06 (d, J = 12.8 Hz, 1H), 3.45–3.36 (m, 1H), 2.01 (d, J = 14.0 Hz, 1H), 1.98–1.80 (m, 3H); cis-isomer: 7.96 (d, J = 7.6 Hz, 1H), 7.64–7.36 (m, 7H), 4.67–4.63 (m, 2H), 4.19 (d, J = 11.2 Hz, 1H), 3.09–2.98 (m, 1H), 2.33 (d, J = 9.6 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 203.5, 203.2, 202.8, 202.7, 202.2, 201.5, 201.2, 146.1, 144.0, 143.1, 142.8, 142.6, 142.4, 141.6, 141.4, 139.1, 139.1, 136.8, 135.5, 135.2, 135.0, 134.9, 134.8, 134.7, 131.0, 130.8, 130.5, 130.2, 129.1, 129.0, 128.6, 128.5, 128.3, 127.9, 127.9, 127.0, 126.9, 122.9, 122.8, 122.7, 122.4, 122.3, 122.2, 118.8, 118.4, 115.4, 115.2, 114.6, 110.0, 63.8, 63.4, 62.7, 61.9, 56.1, 53.7, 52.5, 51.4, 45.6, 43.7, 31.3, 31.2, 20.7, 20.6; IR (KBr) ν: 3026, 1704, 1596, 1499, 1347, 1248, 1153, 1032, 959, 882, 754 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₁H₃₂NO₄ ([M + H]⁺), 602.2331; found, 602.2330.

4.48. 2′-(2-Fluorophenyl)-4′-phenyl-6′-(phenylamino)dispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraone (5c)

The product is obtained as a yellow solid, 92%, 0.289 g, mp 166–169 °C; ¹H NMR (400 MHz, CDCl₃): δ trans-isomer: 8.11 (d, J = 8.0 Hz, 1H), 7.74 (t, J = 8.0 Hz, 1H), 7.67–7.43 (m, 6H), 7.11–6.96 (m, 8H), 6.79–6.36 (m, 7H), 5.07–4.96 (m, 2H), 4.86 (s, 1H), 3.92 (d, J = 16.0 Hz, 1H), 3.57–3.48 (m, 1H), 2.01 (d, J = 16.0 Hz, 1H); cis-isomer: 7.97 (d, J = 8.0 Hz, 1H), 7.67–7.43 (m, 7H), 6.79–6.36 (m, 8H), 5.26 (s, 1H), 4.66 (t, J = 12.6 Hz, 1H), 4.36 (d, J = 12.8 Hz, 1H), 4.26 (d, J = 12.8 Hz, 1H), 3.20–3.11 (m, 1H), 2.38 (d, J = 16.8 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 202.2, 202.2, 202.1, 202.1, 202.1, 201.6, 201.4, 158.4, 146.0, 143.9, 142.5, 142.3, 141.3, 138.9, 135.6, 135.1, 135.0, 132.3, 129.1, 129.0, 128.8, 128.6, 128.0, 128.0, 127.0, 122.9, 122.8, 122.5, 122.3, 119.0, 115.5, 115.2, 114.7, 62.7, 62.5, 56.0, 54.2, 45.4, 43.6, 42.4, 31.6, 31.4; IR (KBr) ν: 3049, 2093, 1705, 1595, 1496, 1447, 1342, 1247, 1102, 957, 885, 760 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₀H₂₈FNNaO₄ ([M + Na]⁺), 628.1900; found, 628.1902.

4.49. 4′-((3-Chlorophenyl)amino)-2′-(2-fluorophenyl)-6′-phenyldispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraone (5d)

The product is obtained as a yellow solid, 90%, 0.298 g, mp 186–187 °C; ¹H NMR (600 MHz, CDCl₃): δ trans-isomer: 8.11 (d, J = 7.5 Hz, 1H), 7.76 (t, J = 7.1 Hz, 1H), 7.62–7.52 (m, 3H), 7.49–7.43 (m, 3H), 7.11–7.07 (m, 2H), 7.04–6.91 (m, 4H), 6.86–6.69 (m, 2H), 6.59–6.54 (m, 3H), 6.47–6.33 (m, 2H), 5.03 (d, J = 13.7 Hz, 1H), 4.95 (t, J = 18.6 Hz, 1H), 4.85 (s, 1H), 4.03 (d, J = 11.9 Hz, 1H), 3.57–3.51 (m, 1H), 1.99 (d, J = 15.2 Hz, 1H); cis-isomer: 8.00 (d, J = 7.1 Hz, 1H), 7.68 (t, J = 7.7 Hz, 1H), 7.49–7.43 (m, 4H), 6.86–6.69 (m, 3H), 6.47–6.33 (m, 4H), 5.24 (s, 1H), 4.61 (br s, 1H), 4.38 (d, J = 12.3 Hz, 2H), 3.19–3.13 (m, 1H), 2.36 (d, J = 16.2 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 202.1, 201.9, 201.5, 201.3, 160.9, 158.4, 147.2, 143.8, 142.4, 142.2, 141.3, 138.7, 135.8, 135.6, 135.3, 135.2, 135.0, 134.8, 134.7, 132.3, 130.1, 130.0, 129.3, 129.2, 128.7, 128.6, 128.0, 127.1, 123.1, 123.0, 122.8, 122.5, 122.3, 118.8, 118.2, 115.5, 115.3, 114.9, 114.2, 113.2, 112.7, 62.6, 62.4, 62.3, 55.5, 53.7, 53.4, 45.1, 43.6, 42.4, 31.5, 31.3; IR (KBr) ν: 3063, 1706, 1591, 1486, 1343, 1246, 1088, 991, 958, 882, 763 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₀H₂₇ClFNNaO₄ ([M + Na]⁺), 662.1510; found, 662.1503.

4.50. 2′-(2-Chlorophenyl)-4′-phenyl-6′-(phenylamino)dispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraone (5e)

The product is obtained as a yellow solid, 88%, 0.273 g, mp 162–164 °C; ¹H NMR (400 MHz, CDCl₃): δ trans-isomer: 8.10 (d, J = 6.8 Hz, 1H), 7.73 (t, J = 6.8 Hz, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.57–7.43 (m, 5H), 7.15–6.83 (m, 9H), 6.69–6.47 (m, 5H), 5.15–5.01 (m, 3H), 3.80 (d, J = 12.0 Hz, 1H), 3.60–3.51 (m, 1H), 2.02 (d, J = 13.6 Hz, 1H); cis-isomer: 7.92 (d, J = 6.8 Hz, 1H), 7.62 (d, J = 8.0 Hz, 2H), 5.43 (s, 1H), 4.73 (t, J = 11.4 Hz, 1H), 4.37 (d, J = 12.4 Hz, 1H), 4.26 (d, J = 11.6 Hz, 1H), 3.28–3.18 (m, 1H), 2.40 (d, J = 13.6 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 202.3, 202.0, 201.6, 201.1, 149.8, 146.1, 144.0, 142.5, 142.4, 141.5, 138.9, 135.5, 135.3, 135.1, 135.0, 134.7, 132.7, 131.7, 131.6, 130.0, 129.7, 129.1, 129.1, 129.0, 128.8, 128.5, 128.4, 127.9, 127.0, 125.9, 125.5, 122.9, 122.6, 122.5, 122.3, 119.0, 118.5, 115.2, 114.7, 63.2, 62.3, 62.2, 62.0, 55.8, 54.6, 47.3, 45.6, 45.1, 43.6, 32.1, 31.4, 15.0; IR (KBr) ν: 3058, 1739, 1704, 1597, 1501, 1325, 1247, 1041, 761 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₀H₂₉ClNO₄ ([M + H]⁺), 622.1785; found, 622.1788.

4.51. 2′-(2-Chlorophenyl)-4′-((3-chlorophenyl)amino)-6′-phenyldispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraone (5f)

The product is obtained as a yellow solid, 91%, 0.298 g, mp 166–170 °C; ¹H NMR (400 MHz, CDCl₃): δ trans-isomer: 8.10 (d, J = 9.2 Hz, 1H), 7.75 (t, J = 6.4 Hz, 1H), 7.68–7.42 (m, 6H), 7.15–6.81 (m, 8H), 6.69–6.52 (m, 2H), 6.47 (d, J = 8.0 Hz, 1H), 6.37 (t, J = 9.4 Hz, 2H), 5.12–5.08 (m, 2H), 4.99 (t, J = 10.4 Hz, 1H), 3.90 (d, J = 11.2 Hz, 1H), 3.62–3.52 (m, 1H), 2.00 (d, J = 15.2 Hz, 1H); cis-isomer: 7.96 (d, J = 8.4 Hz, 1H), 7.68–7.42 (m, 7H), 6.69–6.52 (m, 3H), 5.41 (s, 1H), 4.70–4.64 (m, 1H), 4.42–4.38 (m, 2H), 3.28–3.18 (m, 1H), 2.40–2.36 (m, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 203.0, 202.1, 201.8, 201.3, 201.1, 201.0, 199.8, 147.3, 147.3, 143.9, 142.8, 142.7, 142.5, 142.3, 142.2, 141.5, 138.8, 138.7, 135.6, 135.3, 135.1, 134.8, 134.8, 134.6, 132.7, 132.1, 131.6, 131.5, 130.1, 130.0, 129.8, 129.0, 128.8, 128.5, 128.0, 127.1, 125.9, 123.0, 122.9, 122.5, 118.3, 115.0, 114.3, 114.2, 112.7, 63.1, 62.2, 62.0, 61.9, 55.4, 47.3, 47.2, 45.6, 45.5, 44.9, 31.4; IR (KBr) ν: 33 064, 1739, 1704, 1593, 1480, 1327, 1246, 1159, 1084, 1039, 989, 852, 764 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₀H₂₈Cl₂NO₄ ([M + H]⁺), 656.1395; found, 656.1390.

4.52. 2′-(2-Chlorophenyl)-4′-((4-methoxyphenyl)amino)-6′-phenyldispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraone (5g)

The product is obtained as a yellow solid, 88%, 0.287 g, mp 158–160 °C; ¹H NMR (400 MHz, CDCl₃): δ trans-isomer: 8.08 (d, J = 7.4 Hz, 1H), 7.72 (t, J = 7.3 Hz, 1H), 7.61 (d, J = 7.7 Hz, 1H), 7.57–7.41 (m, 5H), 7.15–7.09 (m, 2H), 7.02–6.83 (m, 5H), 6.68–6.43 (m, 6H), 5.14 (d, J = 12.3 Hz, 1H), 5.06 (s, 1H), 4.94–4.89 (m, 1H), 3.65 (s, 3H), 3.56–3.47 (m, 2H), 2.02 (d, J = 14.9 Hz, 1H); cis-isomer: 7.89 (d, J = 6.8 Hz, 1H), 7.05 (d, J = 7.7 Hz, 1H), 5.41 (s, 1H), 4.32 (d, J = 10.9 Hz, 1H), 4.00 (d, J = 13.3 Hz, 1H), 3.68 (s, 1H), 3.60 (s, 3H), 3.26–3.16 (m, 1H), 2.39 (d, J = 12.9 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 202.3, 201.9, 201.7, 201.1, 153.1, 144.1, 142.4, 142.4, 141.5, 140.0, 138.9, 135.3, 135.0, 134.6, 132.7, 131.7, 129.7, 129.0, 128.8, 128.5, 127.9, 127.0, 125.4, 122.8, 122.7, 122.5, 122.3, 117.2, 117.1, 114.6, 114.5, 63.3, 62.3, 56.4, 56.2, 55.7, 55.5, 47.4, 47.2, 43.6, 43.4, 31.8; IR (KBr) ν: 3040, 1739, 1704, 1593, 1513, 1447, 1329, 1248, 1177, 1130, 1032, 825, 766 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₁H₃₀ClNNaO₅ ([M + Na]⁺), 674.1710; found, 674.1705.

4.53. 2′-(4-Bromophenyl)-4′-phenyl-6′-(phenylamino)dispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraone (5h)

The product is obtained as a yellow solid, 87%, 0.290 g, mp 180–182 °C; ¹H NMR (400 MHz, CDCl₃): δ trans-isomer: 8.09 (d, J = 7.6 Hz, 1H), 7.75 (t, J = 7.6 Hz, 1H), 7.68–7.35 (m, 6H), 7.05–6.80 (m, 9H), 6.68–6.41 (m, 5H), 4.92 (d, J = 12.4 Hz, 2H), 4.28–4.23 (m, 1H), 4.00 (d, J = 11.6 Hz, 1H), 3.41–3.32 (m, 1H), 2.00 (d, J = 14.0 Hz, 1H); cis-isomer: 7.96 (d, J = 7.6 Hz, 1H), 7.68–7.35 (m, 7H), 6.68–6.41 (m, 6H), 4.68 (d, J = 1.6 Hz, 1H), 4.60 (s, 1H), 3.45–3.36 (m, 1H), 4.15 (d, J = 11.6 Hz, 1H), 3.04–2.94 (m, 1H), 2.32 (d, J = 13.6 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 203.2, 202.8, 202.6, 202.4, 201.9, 201.3, 201.1, 200.8, 146.0, 145.9, 143.8, 142.8, 142.4, 142.3, 142.3, 141.5, 141.4, 138.8, 138.7, 135.8, 135.5, 135.3, 135.3, 135.1, 133.4, 132.9, 132.5, 131.0, 130.8, 129.1, 129.0, 128.5, 128.4, 128.0, 128.0, 127.1, 127.1, 123.0, 122.9, 122.6, 122.5, 122.4, 122.3, 121.6, 119.0, 118.6, 115.3, 114.7, 63.6, 63.2, 62.4, 61.7, 56.2, 53.9, 51.8, 50.6, 45.9, 43.9, 31.3, 31.2; IR (KBr) ν: 3053, 1737, 1701, 1595, 1494, 1332, 1248, 1078, 1006, 959, 762 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₀H₂₉BrNO₄ ([M + H]⁺), 666.1280; found, 666.1274.

4.54. 2′-(2-Bromophenyl)-4′-phenyl-6′-(phenylamino)dispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraone (5i)

The product is obtained as a yellow solid, 90%, 0.300 g, mp 163–164 °C; ¹H NMR (400 MHz, CDCl₃): δ trans-isomer: 8.09 (d, J = 3.6 Hz, 1H), 7.73 (t, J = 7.0 Hz, 1H), 7.66–7.42 (m, 6H), 7.16–6.90 (m, 9H), 6.68–6.49 (m, 5H), 5.14 (d, J = 10.0 Hz, 1H), 5.08–5.03 (m, 2H), 3.74 (d, J = 12.8 Hz, 1H), 3.55–3.51 (m, 1H), 2.03 (d, J = 14.8 Hz, 1H); cis-isomer: 7.90 (d, J = 8.4 Hz, 1H), 7.66–7.42 (m, 7H), 5.37 (s, 1H), 4.79–4.74 (m, 1H), 4.37 (d, J = 7.6 Hz, 1H), 4.25 (d, J = 10.8 Hz, 1H), 3.30–3.19 (m, 1H), 2.42 (d, J = 12.8 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 203.1, 202.3, 202.1, 202.0, 201.3, 201.0, 200.7, 199.9, 146.1, 144.1, 143.0, 142.7, 142.4, 142.3, 141.6, 139.0, 138.9, 135.5, 135.3, 135.2, 135.1, 135.0, 134.0, 133.6, 133.5, 133.2, 132.8, 131.7, 129.2, 129.1, 129.0, 128.9, 128.7, 128.6, 128.0, 127.9, 127.0, 126.5, 126.1, 125.9, 125.7, 122.9, 122.9, 122.6, 122.5, 122.3, 119.0, 118.5, 115.5, 115.2, 114.7, 63.5, 62.1, 62.1, 55.8, 54.7, 50.2, 48.3, 45.1, 43.6, 32.3, 31.4; IR (KBr) ν: 3056, 1737, 1703, 1595, 1501, 1320, 1246, 1025, 760 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₀H₂₉BrNO₄ ([M + H]⁺), 666.1280; found, 666.1272.

4.55. 2′-(2-Bromophenyl)-4′-phenyl-6′-(p-tolylamino)dispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraone (5j)

The product is obtained as a yellow solid, 92%, 0.313 g, mp 160–161 °C; ¹H NMR (400 MHz, CDCl₃): δ trans-isomer: 8.08 (d, J = 8.1 Hz, 1H), 7.72 (t, J = 8.1 Hz, 1H), 7.66–7.61 (m, 1H), 7.57–7.41 (m, 5H), 7.15–6.84 (m, 9H), 6.61–6.52 (m, 4H), 5.14 (d, J = 13.2 Hz, 1H), 5.04–4.98 (m, 2H), 3.60 (d, J = 12.7 Hz, 1H), 3.55–3.47 (m, 1H), 2.13 (s, 3H), 2.05–2.00 (m, 1H); cis-isomer: 7.89 (d, J = 5.4 Hz, 1H), 7.66–7.61 (m, 2H), 6.73 (d, J = 8.0 Hz, 1H), 6.42 (d, J = 8.4 Hz, 1H), 5.36 (s, 1H), 4.72 (br s, 1H), 4.33 (d, J = 16.2 Hz, 1H), 4.10 (d, J = 11.1 Hz, 1H), 3.27–3.17 (m, 1H), 2.40 (d, J = 12.7 Hz, 1H), 2.07 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 202.3, 202.1, 201.4, 201.0, 144.1, 143.8, 142.5, 142.5, 141.7, 139.0, 135.4, 135.1, 133.6, 133.2, 132.8, 129.6, 129.2, 128.9, 128.7, 128.4, 127.9, 127.0, 126.1, 125.8, 122.8, 122.6, 122.3, 115.6, 115.5, 63.5, 62.2, 55.4, 50.2, 50.1, 43.7, 32.1, 20.3; IR (KBr) ν: 2918, 1740, 1705, 1598, 1516, 1326, 1247, 1024, 817, 762, 700 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₁H₃₁BrNO₄ ([M + H]⁺), 680.1436; found, 680.1420.

4.56. 2′-(2-Bromophenyl)-4′-((4-methoxyphenyl)amino)-6′-phenyldispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraone (5k)

The product is obtained as a yellow solid, 90%, 0.313 g, mp 154–156 °C; ¹H NMR (400 MHz, CDCl₃): δ trans-isomer: 8.07 (d, J = 7.8 Hz, 1H), 7.72 (t, J = 7.3 Hz, 1H), 7.64 (d, J = 8.0 Hz, 1H), 7.57–7.41 (m, 5H), 7.16–6.91 (m, 7H), 6.62–6.45 (m, 6H), 5.15 (d, J = 13.3 Hz, 1H), 5.03 (s, 1H), 4.94 (t, J = 9.6 Hz, 1H), 3.66 (s, 3H), 3.53–3.46 (m, 2H), 2.03 (d, J = 12.9 Hz, 1H); cis-isomer: 7.87 (d, J = 8.6 Hz, 1H), 7.16–6.91 (m, 8H), 5.35 (s, 1H), 4.68 (br s, 1H), 4.31 (d, J = 11.9 Hz, 1H), 3.98 (d, J = 13.2 Hz, 1H), 3.60 (s, 3H), 3.27–3.18 (m, 1H), 2.39 (d, J = 12.8 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 202.3, 202.0, 201.5, 201.0, 153.2, 144.1, 142.5, 142.4, 141.7, 140.0, 139.0, 135.4, 135.1, 135.0, 133.5, 133.2, 132.8, 129.2, 128.9, 127.9, 127.0, 125.8, 122.8, 122.6, 117.2, 114.6, 63.6, 62.2, 56.4, 55.7, 43.6, 32.0; IR (KBr) ν: 3038, 1740, 1705, 1593, 1511, 1445, 1329, 1245, 1184, 1127, 1031, 829, 766 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₁H₃₁BrNO₅ ([M + H]⁺), 696.1386; found, 696.1373.

4.57. 2′-(2-Bromophenyl)-4′-((4-methoxyphenyl)amino)-6′-(p-tolyl)dispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraone (5l)

The product is obtained as a yellow solid, 93%, 0.330 g, mp 160–163 °C; ¹H NMR (400 MHz, CDCl₃): δ trans-isomer: 8.07 (d, J = 7.8 Hz, 1H), 7.73–7.61 (m, 2H), 7.56–7.42 (m, 5H), 7.07–7.00 (m, 4H), 6.85 (d, J = 6.9 Hz, 2H), 6.60–6.51 (m, 6H), 5.10 (d, J = 15.0 Hz, 1H), 5.01–4.96 (m, 2H), 3.60 (s, 3H), 3.57–3.44 (m, 2H), 2.13 (s, 3H), 1.99 (d, J = 15.3 Hz, 1H); cis-isomer: 7.88 (d, J = 7.6 Hz, 1H), 6.72 (d, J = 8.0 Hz, 2H), 6.41 (d, J = 6.6 Hz, 2H), 5.33 (s, 1H), 4.72 (br s, 1H), 4.28 (d, J = 12.9 Hz, 1H), 4.08 (d, J = 12.2 Hz, 1H), 3.06 (s, 3H), 3.23–3.14 (m, 1H), 2.36 (d, J = 13.6 Hz, 1H), 2.13 (s, 1H), 2.07 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 202.5, 202.1, 201.5, 201.2, 158.3, 144.1, 143.8, 142.6, 142.5, 141.7, 135.4, 135.1, 135.0, 133.6, 133.2, 132.7, 131.1, 130.2, 129.6, 128.4, 125.8, 122.8, 113.3, 63.5, 62.2, 55.0, 50.2, 32.5, 20.3; IR (KBr) ν: 2924, 1740, 1705, 1602, 1512, 1464, 1337, 1248, 1175, 1122, 1028, 835, 763, 726 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₂H₃₃BrNO₅ ([M + H]⁺), 710.1542; found, 710.1531.

4.58. 2′-(2-Bromophenyl)-4′-(4-methoxyphenyl)-6′-((4-methoxyphenyl)amino)dispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraone (5m)

The product is obtained as a yellow solid, 88%, 0.319 g, mp 137–142 °C; ¹H NMR (400 MHz, CDCl₃): δ trans-isomer: 8.06 (d, J = 7.4 Hz, 1H), 7.73–7.60 (m, 2H), 7.56–7.39 (m, 5H), 7.08–6.99 (m, 4H), 6.62–6.45 (m, 8H), 5.12–5.08 (m, 1H), 5.00 (s, 1H), 4.92 (t, J = 15.0 Hz, 1H), 3.66 (s, 3H), 3.61 (s, 3H), 3.52–3.43 (m, 2H), 1.99 (d, J = 13.1 Hz, 1H); cis-isomer: 7.86 (d, J = 6.6 Hz, 1H), 5.32 (s, 1H), 4.67 (br s, 1H), 4.26 (d, J = 11.6 Hz, 1H), 3.97 (d, J = 10.8 Hz, 1H), 3.19 (d, J = 10.8 Hz, 1H), 2.35 (d, J = 7.8 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 202.5, 202.0, 201.5, 201.2, 158.3, 153.1, 144.1, 142.6, 142.4, 141.7, 140.1, 135.7, 135.4, 135.1, 135.0, 133.6, 133.2, 132.7, 131.5, 131.1, 130.2, 129.9, 128.7, 126.1, 125.8, 122.8, 122.5, 122.3, 117.2, 114.6, 114.4, 113.3, 63.6, 62.3, 56.4, 55.7, 55.6, 55.0, 55.0, 50.3, 50.2, 44.5, 42.8, 32.3; IR (KBr) ν: 3061, 2930, 2830, 1738, 1703, 1598, 1511, 1458, 1343, 1242, 1174, 1104, 1034, 960, 827, 765 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₂H₃₃BrNO₆ ([M + H]⁺), 726.1491; found, 726.1485.

4.59. 2′-(2-Bromophenyl)-4′-(4-fluorophenyl)-6′-((4-methoxyphenyl)amino)dispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraone (5n)

The product is obtained as a yellow solid, 85%, 0303 g, mp 146–148 °C; ¹H NMR (400 MHz, CDCl₃): δ trans-isomer: 8.08 (d, J = 9.0 Hz, 1H), 7.75–7.69 (m, 2H), 7.62–7.39 (m, 5H), 7.12–6.90 (m, 7H), 6.67–6.47 (m, 5H), 5.14 (d, J = 12.8 Hz, 1H), 5.06–4.01 (m, 2H), 3.70 (d, J = 12.7 Hz, 1H), 3.56–3.48 (m, 1H), 1.99 (d, J = 15.8 Hz, 1H); cis-isomer: 7.90 (d, J = 8.3 Hz, 1H), 7.12–6.90 (m, 8H), 5.33 (s, 1H), 4.74 (br s, 1H), 4.36 (d, J = 14.0 Hz, 1H), 4.23 (d, J = 12.8 Hz, 1H), 3.27–3.17 (m, 1H), 2.37 (d, J = 11.0 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 202.3, 202.0, 201.3, 201.0, 162.8, 160.4, 153.2, 144.0, 142.5, 142.4, 141.6, 139.9, 135.4, 135.3, 135.2, 135.1, 134.8, 133.4, 133.2, 132.6, 130.8, 130.7, 130.4, 128.7, 126.1, 125.8, 122.8, 122.6, 122.3, 117.2, 114.8, 114.6, 63.5, 62.1, 56.2, 55.6, 50.2, 50.2, 32.1.; IR (KBr) ν: 3064, 1740, 1705, 1595, 1511, 1339, 1245, 1169, 1121, 1030, 832, 764, 728 cm^–1; MS (m/z): HRMS (ESI-TOF) calcd for C₄₁H₃₀BrFNO₅ ([M + H]⁺), 714.1291; found, 714.1280.

Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (nos. 21572196), the Priority Academic Program Development of Jiangsu Higher Education Institutions (no. BK2013016).

Supporting Information Available

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsomega.9b01960.

Copies of the ¹H and ¹³C{¹H} NMR spectra for all new products (PDF)
Crystallographic data of compounds 3e (CCDC 1917510), 3g (CCDC 1917511), 3i (CCDC 1917512), 3l (CCDC 1917513), 3p (CCDC 1917514), 4f (CCDC 1917515), 4m (CCDC 1917516), 5g (CCDC 1917517), and 5i (CCDC 1917518) have been deposited at the Cambridge Crystallographic Database Center (http://www.ccdc.cam.ac.uk) (CIF)

The authors declare no competing financial interest.

Supplementary Material

ao9b01960_si_001.pdf^{(9.6MB, pdf)}

ao9b01960_si_002.cif^{(13.5MB, cif)}

References

a Zhang J.; El-Shabrawy A.-R. O.; El-Shanawany M. A.; Schiff P. L.; Slatkin D. J. New azafluorene alkaloids from Oxandra xylopioides. J. Nat. Prod. 1987, 50, 800–806. 10.1021/np50053a005. [DOI] [Google Scholar]; b Nugiel D. A.; Etzkorn A.-M.; Vidwans A.; Benfield P. A.; Boisclair M.; Burton C. R.; Cox S.; Czerniak P. M.; Doleniak D.; Seitz S. P. Indenopyrazoles as Novel Cyclin Dependent Kinase (CDK) Inhibitors. J. Med. Chem. 2001, 44, 1334–1336. 10.1021/jm0100032. [DOI] [PubMed] [Google Scholar]; c Frédérick R.; Dumont W.; Ooms F.; Aschenbach L.; Van der Schyf C. J.; Castagnoli N.; Wouters J.; Krief A. Synthesis, Structural Reassignment, and Biological Activity of Type B MAO Inhibitors Based on the 5H-Indeno[1,2-c]pyridazin-5-one Core. J. Med. Chem. 2006, 49, 3743–3747. 10.1021/jm051091j. [DOI] [PubMed] [Google Scholar]
a Miri R.; Javidnia K.; Hemmateenejad B.; Azarpira A.; Amirghofran Z. Synthesis, cytotoxicity, QSAR, and intercalation study of new diindenopyridine derivatives. Bioorg. Med. Chem. 2004, 12, 2529–2536. 10.1016/j.bmc.2004.03.032. [DOI] [PubMed] [Google Scholar]; b Safak C.; Simsek R.; Altas Y.; Boydag S.; Erol K. 2-Methyl-3-acetyl-4-aryl-5-oxo-1,4-dihydro-5H-indeno (1,2-b) pyridine derivative studies and their calcium antagonistic activities. Boll. Chim. Farm. 1997, 136, 665–669. [PubMed] [Google Scholar]
Nicolaou K. C.; Montagnon T.; Vassilikogiannakis G.; Mathison C. J. N. The Total Synthesis of Coleophomones B, C, and D. J. Am. Chem. Soc. 2005, 127, 8872–8888. 10.1021/ja0509984. [DOI] [PubMed] [Google Scholar]
a Addla D.; Bhima; Sridhar B.; Devi A.; Kantevari S. Design, synthesis and antimicrobial evaluation of novel 1-benzyl 2-butyl-4-chloroimidazole embodied 4-azafluorenones via molecular hybridization approach. Bioorg. Med. Chem. Lett. 2012, 22, 7475–7480. 10.1016/j.bmcl.2012.10.042. [DOI] [PubMed] [Google Scholar]; b Chakrabarty S.; Croft M. S.; Marko M. G.; Moyna G. Synthesis and evaluation as potential anticancer agents of novel tetracyclic indenoquinoline derivatives. Bioorg. Med. Chem. 2013, 21, 1143–1149. 10.1016/j.bmc.2012.12.026. [DOI] [PubMed] [Google Scholar]; c Muscia G. C.; Buldain G. Y.; Asís S. E. Design, synthesis and evaluation of acridine and fused-quinoline derivatives as potential anti-tuberculosis agents. Eur. J. Med. Chem. 2014, 73, 243–249. 10.1016/j.ejmech.2013.12.013. [DOI] [PubMed] [Google Scholar]
Nagarajan M.; Morrell A.; Fort B. C.; Meckley M. R.; Antony S.; Kohlhagen G.; Pommier Y.; Cushman M. Synthesis and anticancer activity of simplified indenoisoquinoline topoisomerase I inhibitors lacking substituents on the aromatic rings. J. Med. Chem. 2004, 47, 5651. 10.1021/jm040025z. [DOI] [PubMed] [Google Scholar]
a Pizzirani D.; Roberti M.; Grimaudo S.; Di Cristina A.; Pipitone R. M.; Tolomeo M.; Recanatini M. Identification of Biphenyl-Based Hybrid Molecules Able To Decrease the Intracellular Level of Bcl-2 Protein in Bcl-2 Overexpressing Leukemia Cells. J. Med. Chem. 2009, 52, 6936–6940. 10.1021/jm900907s. [DOI] [PubMed] [Google Scholar]
Wu X.; Li X.; Li Z.; Yu Y.; You Q.; Zhang X. Discovery of Nonquinone Substrates for NAD(P)H: Quinone Oxidoreductase 1 (NQO1) as Effective Intracellular ROS Generators for the Treatment of Drug-Resistant Non-Small-Cell Lung Cancer. J. Med. Chem. 2018, 61, 11280–11297. 10.1021/acs.jmedchem.8b01424. [DOI] [PubMed] [Google Scholar]
a Huang H.-H.; Prabhakar C.; Tang K.-C.; Chou P.-T.; Huang G.-J.; Yang J.-S. Ortho-Branched Ladder-Type Oligophenylenes with Two-Dimensionally π-Conjugated Electronic Properties. J. Am. Chem. Soc. 2011, 133, 8028–8039. 10.1021/ja202144v. [DOI] [PubMed] [Google Scholar]; b Gómez-Esteban S.; Benito-Hernandez A.; Termine R.; Hennrich G.; Navarrete J. T. L.; Ruiz Delgado M. C.; Golemme A.; Gómez-Lor B. High-Mobility Self-Assembling Truxenone-Based n-Type Organic Semiconductors. Chem.—Eur. J. 2018, 24, 3576–3583. 10.1002/chem.201705760. [DOI] [PubMed] [Google Scholar]; c Sanguinet L.; Williams J. C.; Yang Z.; Twieg R. J.; Mao G.; Singer K. D.; Wiggers G.; Petschek R. G. Synthesis and Characterization of New Truxenones for Nonlinear Optical Applications. Chem. Mater. 2006, 18, 4259–4269. 10.1021/cm0601887. [DOI] [Google Scholar]; d Chaudhri N.; Grover N.; Sankar M. Nickel-Induced Skeletal Rearrangement of Free Base trans-Chlorins into Monofused NiII-Porphyrins: Synthesis, Structural, Spectral, and Electrochemical Redox Properties. Inorg. Chem. 2018, 57, 11349–11360. 10.1021/acs.inorgchem.8b00798. [DOI] [PubMed] [Google Scholar]; e Zatsikha Y. V.; Schrage B. R.; Meyer J.; Nemykin V. N.; Ziegler C. J. 1,3-Diylideneisoindolines: Synthesis, Structure, Redox, and Optical Properties. J. Org. Chem. 2019, 84, 6217–6222. 10.1021/acs.joc.9b00468. [DOI] [PubMed] [Google Scholar]
a Vilches-Herrera M.; Knepper I.; de Souza N.; Villinger A.; Sosnovskikh V. Y.; Iaroshenko V. O. One-pot, three-component synthesis of 7-azaindole derivatives from N-substituted 2-amino-4-cyanopyrroles, various aldehydes, and active methylene compounds. ACS Comb. Sci. 2012, 14, 434–441. 10.1021/co300042v. [DOI] [PubMed] [Google Scholar]; b Khurana J. M.; Chaudhary A.; Nand B.; Lumb A. Aqua mediated indium(III) chloride catalyzed synthesis of fused pyrimidines and pyrazoles. Tetrahedron Lett. 2012, 53, 3018–3022. 10.1016/j.tetlet.2012.04.001. [DOI] [Google Scholar]; c Siddiqui Z. N.; Khan K. Friedlander synthesis of novel benzopyranopyridines in the presence of chitosan as heterogeneous, efficient and biodegradable catalyst under solvent-free conditions. New J. Chem. 2013, 37, 1595–1602. 10.1039/c3nj00069a. [DOI] [Google Scholar]; d Ray S.; Brown M.; Bhaumik A.; Dutta A.; Mukhopadhyay C. A new MCM-41 supported HPF6 catalyst for the library synthesis of highly substituted 1,4-dihydropyridines and oxidation to pyridines: report of one-dimensional packing towards LMSOMs and studies on their photophysical properties. Green Chem. 2013, 15, 1910–1924. 10.1039/c3gc40441b. [DOI] [Google Scholar]
a Zhou Y.-J.; Chen D.-S.; Li Y.-L.; Liu Y.; Wang X.-S. Combinatorial Synthesis of Pyrrolo[3,2-f]quinoline and Pyrrolo[3,2-a]acridine Derivatives via a Three-Component Reaction under Catalyst-Free Conditions. ACS Comb. Sci. 2013, 15, 498–502. 10.1021/co400073m. [DOI] [PubMed] [Google Scholar]; b Chen M.; Sun N.; Liu Y. Environmentally benign synthesis of indeno[1,2-b]quinolines via an intramolecular Povarov reaction. Org. Lett. 2013, 15, 5574–5577. 10.1021/ol402775k. [DOI] [PubMed] [Google Scholar]; c Allais C.; Liéby-Muller F.; Rodriguez J.; Constantieux T. Metal-Free Michael-Addition-Initiated Three-Component Reaction for the Regioselective Synthesis of Highly Functionalized Pyridines: Scope, Mechanistic Investigations and Applications. Eur. J. Org. Chem. 2013, 4131–4145. 10.1002/ejoc.201300246. [DOI] [Google Scholar]; d Marquise N.; Dorcet V.; Chevallier F.; Mongin F. Synthesis of substituted azafluorenones from dihalogeno diaryl ketones by palladium-catalyzed auto-tandem processes. Org. Biomol. Chem. 2014, 12, 8138–8141. 10.1039/c4ob01629g. [DOI] [PubMed] [Google Scholar]; e Rao Y.; Liu M.; Wu L.; Yin G. Catalyst-free one-pot domino reactions for selective synthesis of functionalized 2,8-oxazabicyclo[3.3.1]-nonanes and 5H-indeno[1,2-b]pyridin-5-ones. RSC Adv. 2014, 4, 64551–64558. 10.1039/c4ra13166e. [DOI] [Google Scholar]
a Tu S.-J.; Jiang B.; Zhang J.-Y.; Jia R.-H.; Zhang Y.; Yao C.-S. Efficient and direct synthesis of poly-substituted indeno[1,2-b]quinolines assisted by p-toluene sulfonic acid using high-temperature water and microwave heating via one-pot, three-component reaction. Org. Biomol. Chem. 2006, 4, 3980–3985. 10.1039/b611462h. [DOI] [PubMed] [Google Scholar]; b Majumder S.; Sharma M.; Bhuyan P. J. Microwave promoted diastereoselective synthesis of dihydroindeno[1,2-b]furans via one-pot three-component reaction in solvent-free conditions. Tetrahedron Lett. 2013, 54, 6868–6870. 10.1016/j.tetlet.2013.10.023. [DOI] [Google Scholar]; c Ahadi S.; Moafi L.; Feiz A.; Bazgir A. Three-component synthesis of new unsymmetrical oxindoles via Friedel-Crafts type reaction. Tetrahedron 2011, 67, 3954–3958. 10.1016/j.tet.2011.02.054. [DOI] [PMC free article] [PubMed] [Google Scholar]; d Liang B.; Kalidindi S.; Porco J. A.; Stephenson C. R. J. Multicomponent reaction discovery: three-component synthesis of spirooxindoles. Org. Lett. 2010, 12, 572–575. 10.1021/ol902764k. [DOI] [PMC free article] [PubMed] [Google Scholar]
a Tu S.-J.; Jiang B.; Jia R.-H.; Zhang J.-Y.; Zhang Y.; Yao C.-S.; Shi F. An efficient one-pot, three-component synthesis of indeno[1,2-b]quinoline-9,11(6H,10H)-dione, acridine-1,8(2H,5H)-dione and quinoline-3-carbonitrile derivatives from enaminones. Org. Biomol. Chem. 2006, 4, 3664–3668. 10.1039/b607575d. [DOI] [PubMed] [Google Scholar]; b Ghahremanzadeh R.; Imani Shakibaei G.; Ahadi S.; Bazgir A. One-Pot, Pseudo Four-Component Synthesis of a Spiro[diindeno[1,2-b:2′,1′-e]pyridine-11,3′-indoline]-trione Library. J. Comb. Chem. 2010, 12, 191–194. 10.1021/cc900130a. [DOI] [PubMed] [Google Scholar]; c Ghahremanzadeh R.; Ahadi S.; Shakibaei G. I.; Bazgir A. Grindstone chemistry: one-pot synthesis of spiro[diindenopyridine-indoline]triones and spiro[acenaphthylene-diindenopyridine]triones. Tetrahedron Lett. 2010, 51, 499–502. 10.1016/j.tetlet.2009.11.041. [DOI] [Google Scholar]; d Mondal A.; Mukhopadhyay C. FeCl3-Catalyzed Combinatorial Synthesis of Functionalized Spiro[Indolo-3,10′-indeno [1,2-b]quinolin]-trione Derivatives. ACS Comb. Sci. 2015, 17, 404–408. 10.1021/acscombsci.5b00038. [DOI] [PubMed] [Google Scholar]; e Mondal A.; Banerjee B.; Bhaumik A.; Mukhopadhyay C. Activated Alumina Balls under Neat Conditions: A Green Catalyst for the Synthesis of Spiro-Heterocyclic Scaffolds by Ring-Opening versus Annulation of the Isatin Moiety. ChemCatChem 2016, 8, 1185–1198. 10.1002/cctc.201500885. [DOI] [Google Scholar]
a Tugrak M.; Inci Gul H.; Sakagami H.; Gulcin I.; Supuran C. T. New azafluorenones with cytotoxic and carbonic anhydrase inhibitory properties: 2-Aryl-4-(4-hydroxyphenyl)-5H-indeno[1,2-b]pyridin-5-ones. Bioorg. Chem. 2018, 81, 433–439. 10.1016/j.bioorg.2018.09.013. [DOI] [PubMed] [Google Scholar]; b Jangra H.; Chen Q.; Fuks E.; Zenz I.; Mayer P.; Ofial A. R.; Zipse H.; Mayr H. Nucleophilicity and Electrophilicity Parameters for Predicting Absolute Rate Constants of Highly Asynchronous 1,3-Dipolar Cycloadditions of Aryldiazomethanes. J. Am. Chem. Soc. 2018, 140, 16758–16772. 10.1021/jacs.8b09995. [DOI] [PubMed] [Google Scholar]; c Chen Y.-R.; Ganapuram M. R.; Hsieh K.-H.; Chen K.-H.; Karanam P.; Vagh S. S.; Liou Y.-C.; Lin W. 3-Homoacyl coumarin: an all carbon 1,3-dipole for enantioselective concerted (3+2) cycloaddition. Chem. Commun. 2018, 54, 12702–12705. 10.1039/c8cc07271j. [DOI] [PubMed] [Google Scholar]; d Xu H.; Sha F.; Li Q.; Wu X.-Y. Catalytic asymmetric Tamura cycloaddition of homophthalic anhydrides with 2-arylidene-1,3-diones. Org. Biomol. Chem. 2018, 16, 7214–7222. 10.1039/c8ob01970c. [DOI] [PubMed] [Google Scholar]; e Xu H.; Chen K.; Liu H.-W.; Wang G.-W. Solvent-free N-iodosuccinimide-promoted synthesis of spiroimidazolines from alkenes and amidines under ball-milling conditions. Org. Chem. Front. 2018, 5, 2864–2869. 10.1039/c8qo00723c. [DOI] [Google Scholar]; f Hussein E. M.; Moussa Z.; Ahmed S. A. Exclusive regioselective 1,3-dipolar cycloaddition of 9-diazo-9H-fluorene and diphenyldiazomethane to 2-arylideneindane-1,3-diones: new approach toward effective synthesis of novel spiropyrazole derivatives. Monatsh. Chem. 2018, 149, 2021–2030. 10.1007/s00706-018-2249-0. [DOI] [Google Scholar]
a Meena K.; Kumari S.; Khurana J. M.; Malik A. Efficient syntheses of novel indeno[1,2-b]chromenone derivatives via hetero-Diels-Alder reactions of 2-(arylmethylene)-1H-indene-1,3(2H)-diones with enaminones. Tetrahedron Lett. 2018, 59, 1493–1496. 10.1016/j.tetlet.2018.03.014. [DOI] [Google Scholar]; b Wang M.; Tang B.-C.; Xiang J.-C.; Cheng Y.; Wang Z.-X.; Ma J.-T.; Wu Y.-D.; Wu A.-X. C(sp3)-H Bond Functionalization of Benzo[c]oxepines via C-O bond Cleavage: Formal [3+3] Synthesis of Multisubstituted Chromans. J. Org. Chem. 2018, 83, 3409–3416. 10.1021/acs.joc.8b00126. [DOI] [PubMed] [Google Scholar]; c Qi J.; Zheng J.; Cui S. Facile synthesis of carbo- and heterocycles via Fe(III)-catalyzed alkene hydrofunctionalization. Org. Chem. Front. 2018, 5, 222–225. 10.1039/c7qo00817a. [DOI] [Google Scholar]; d Yu J.-K.; Chien H.-W.; Lin Y.-J.; Karanam P.; Chen Y.-H.; Lin W. Diversity-oriented synthesis of chromenopyrrolidines from azomethine ylides and 2-hydroxybenzylidene indandiones via base-controlled regiodivergent (3+2) cycloaddition. Chem. Commun. 2018, 54, 9921–9924. 10.1039/c8cc05693e. [DOI] [PubMed] [Google Scholar]; e Rapi Z.; Nemcsok T.; Grün A.; Pálvölgyi Á.; Samu G.; Hessz D.; Kubinyi M.; Kállay M.; Keglevich G.; Bakó P. Asymmetric cyclopropanation reactions catalyzed by carbohydrate-based crown ethers. Tetrahedron 2018, 74, 3512–3526. 10.1016/j.tet.2018.04.087. [DOI] [Google Scholar]
a Yang S.-M.; Karanam P.; Wang M.; Jang Y.-J.; Yeh Y.-S.; Tseng P.-Y.; Ganapuram M. R.; Liou Y.-C.; Lin W. A vinylogous Michael addition-triggered quadruple cascade reaction for the enantioselective generation of multiple quaternary stereocenters,. Chem. Commun. 2019, 55, 1398–1401. 10.1039/c8cc09219b. [DOI] [PubMed] [Google Scholar]; b Solanke P.; Pytela O.; Bureš F.; Klikar M. T-shaped D-π-A-(π-A)2 chromophores with two auxiliary electron acceptors. Dyes Pigm. 2019, 162, 755–762. 10.1016/j.dyepig.2018.10.077. [DOI] [Google Scholar]; c Matsuo Y.; Yu C.-G.; Nakagawa T.; Okada H.; Ueno H.; Sun T.-G.; Zhong Y.-W. Reduced Knoevenagel Reaction of Acetetracenylene-1,2-dione with Acceptor Units for Luminescent Tetracene Derivatives. J. Org. Chem. 2019, 84, 2339–2345. 10.1021/acs.joc.8b03083. [DOI] [PubMed] [Google Scholar]
a Baruah B.; Bhuyan P. J. Synthesis of some complex pyrano[2,3-b]- and pyrido[2,3-b]quinolines from simple acetanilides via intramolecular domino hetero Diels-Alder reactions of 1-oxa-1,3-butadienes in aqueous medium. Tetrahedron 2009, 65, 7099–7104. 10.1016/j.tet.2009.06.036. [DOI] [Google Scholar]; b Liu J.; Wang X.; Sun C.-L.; Li B.-J.; Shi Z.-J.; Wang M. New strategy to construct fused/bridged/spiro carbocyclic scaffolds based on the design of novel 6-C synthon precursor. Org. Biomol. Chem. 2011, 9, 1572–1577. 10.1039/c0ob00660b. [DOI] [PubMed] [Google Scholar]; c Xu H.; Sha F.; Li Q.; Wu X.-Y. Catalytic asymmetric Tamura cycloaddition of homophthalic anhydrides with 2-arylidene-1,3-diones. Org. Biomol. Chem. 2018, 16, 7214–7222. 10.1039/c8ob01970c. [DOI] [PubMed] [Google Scholar]
a Bhuyan D.; Sarmah M. M.; Dommaraju Y.; Prajapati D. Microwave-promoted efficient synthesis of spiroindenotetrahydropyridine derivatives via a catalyst- and solvent-free pseudo one-pot five-component tandem Knoevenagel/aza-Diels-Alder reaction. Tetrahedron Lett. 2014, 55, 5133–5136. 10.1016/j.tetlet.2014.07.086. [DOI] [Google Scholar]; b Madhusudhan Reddy G.; Ko C. T.; Hsieh K. H.; Lee C. J.; Das U.; Lin W. W. Expanding the Scope of Primary Amine Catalysis: Stereoselective Synthesis of Indanedione-Fused 2,6-Disubstituted trans-Spirocyclohexanones. J. Org. Chem. 2016, 81, 2420–2431. 10.1021/acs.joc.5b02921. [DOI] [PubMed] [Google Scholar]; c Xi Q.-Z.; Gan Z.-J.; Li E.-Q.; Duan Z. Bronsted Acid Tuned, Lewis Base Promoted [4+2] Annulation Reactions of Allenoates with Electron-Deficient Olefins. Eur. J. Org. Chem. 2018, 4917–4925. 10.1002/ejoc.201800917. [DOI] [Google Scholar]
a Wang X.-H.; Yan C. G. Facile synthesis of spiro[indane-2,1′-pyrrolo[2,1-a]isoquinolines] via three-component reaction of isoquinolinium salts, indane-1,3-dione, and isatins. Synthesis 2014, 46, 1059–1066. 10.1055/s-0033-1340815. [DOI] [Google Scholar]; b Shi R.-G.; Wang X.-H.; Liu R.; Yan C.-G. Two-carbon ring expansion of isatin: a convenient construction of a dibenzo[b,d]azepinone scaffold. Chem. Commun. 2016, 52, 6280–6283. 10.1039/c6cc00525j. [DOI] [PubMed] [Google Scholar]; c Jin G.; Sun J.; Yan C.-G. Formation of zwitterionic salts via three-component reaction of benzimidazolium bromides, aromatic aldehydes and 1,3-indanedione. RSC Adv. 2016, 6, 84379–84387. 10.1039/c6ra16838h. [DOI] [Google Scholar]; d Yang W.-J.; Zhang J.; Sun J.; Yan C.-G. Convenient Construction of Indanedione-Fused 2,5-Dihydropyridines, 4,5-Dihydropyridines, and Spirooxindolines. Eur. J. Org. Chem. 2016, 5423–5428. 10.1002/ejoc.201600981. [DOI] [Google Scholar]; e Shen G.; Sun J.; Yan C. Convenient Synthesis of Spiro[benzo[d]pyrrolo[2,1-b]thiazole-3,2′-indenes] Derivatives via Three-Component Reaction. Chin. J. Chem. 2016, 34, 412–418. 10.1002/cjoc.201500896. [DOI] [Google Scholar]; f Shi R.-G.; Sun J.; Yan C.-G. Tandem Double [3+2] Cycloaddition Reactions at Both C-1 and C-3 Atoms of N-Cyanomethylisoquinolinium Ylide. ACS Omega 2017, 2, 7820–7830. 10.1021/acsomega.7b01391. [DOI] [PMC free article] [PubMed] [Google Scholar]; g Liu R.; Shi R.-G.; Sun J.; Yan C.-G. A [3+2]-[4+2]-[3+2] cycloaddition sequence of isoquinolinium ylide. Org. Chem. Front. 2017, 4, 354–357. 10.1039/c6qo00615a. [DOI] [Google Scholar]; h Chen L.; Sun J.; Huang Y.; Yan C. G. Regioselectivity and diastereoselectivity of three-component reaction of α-amino acid, dialkyl acetylenedicarboxylates and 2-arylidene-1,3-indanediones. Sci. Rep. 2017, 7, 12418. 10.1038/s41598-017-12361-z. [DOI] [PMC free article] [PubMed] [Google Scholar]; i Zhang Y.-Y.; Han Y.; Sun J.; Yan C.-G. Construction of Spiropyrido[2,1-a]isoquinoline via Tandem Reactions of Huisgen’s 1,4-Dipoles with Various Alkene Dipolarophiles. ChemistrySelect 2017, 2, 7382–7386. 10.1002/slct.201701348. [DOI] [Google Scholar]; j Cao J.; Sun J.; Yan C.-G. Regioselective and diastereoselective synthesis of two functionalized 1,5-methanoindeno[1,2-d]azocines via a three-component reaction. Org. Biomol. Chem. 2018, 16, 4170–4175. 10.1039/c8ob00144h. [DOI] [PubMed] [Google Scholar]; k Sun J.; Sun Q.-S.; Yan C.-G. Selective construction of indeno[1,2-b]phenothiazine and indeno[2,1-c]phenothiazine via tandem annulation reaction. Tetrahedron 2018, 74, 2871–2875. 10.1016/j.tet.2018.04.062. [DOI] [Google Scholar]; l Yang R.-Y.; Sun J.; Yan C.-G. HOAc-Mediated Domino Diels-Alder Reaction for Synthesis of Spiro[cyclohexane-1,3′-indolines] in Ionic Liquid [Bmim] Br.. ACS Omega 2018, 3, 5406–5416. 10.1021/acsomega.8b00464. [DOI] [PMC free article] [PubMed] [Google Scholar]; m Sun J.; Zhang Y.; Shi R.-G.; Yan C.-G. Selective synthesis of spirooxindoles via a twostep reaction of N-phenacylpyridinium bromide, 1,3-indanedione and N-alkylisations. Org. Biomol. Chem. 2019, 17, 3978–3983. 10.1039/c9ob00166b. [DOI] [PubMed] [Google Scholar]
Yang W.-J.; Sun Q.; Sun J.; Yan C.-G. Domino aza/oxa-hetero-Diels–Alder reaction for construction of novel spiro[pyrido[3′,2′:5,6]pyrano[2,3-d]pyrimidine-7,5′-pyrimidine]. Org. Chem. Front. 2018, 5, 2754–2758. 10.1039/c8qo00784e. [DOI] [Google Scholar]
Gu R.; Flidrova K.; Lehn J.-M. Dynamic Covalent Metathesis in the C=C/C=N Exchange between Knoevenagel Compounds and Imines. J. Am. Chem. Soc. 2018, 140, 5560–5568. 10.1021/jacs.8b01849. [DOI] [PubMed] [Google Scholar]
Domingo L. R.; Sáez J. A. Understanding the mechanism of polar Diels-Alder reactions. Org. Biomol. Chem. 2009, 7, 3576–3583. 10.1039/b909611f. [DOI] [PubMed] [Google Scholar]
a Chu J. C. K.; Dalton D. M.; Rovis T. Zn-Catalyzed Enantio- and Diastereoselective Formal [4 + 2] Cycloaddition Involving Two Electron-Deficient Partners: Asymmetric Synthesis of Piperidines from 1-Azadienes and Nitro-Alkenes. J. Am. Chem. Soc. 2015, 137, 4445–4452. 10.1021/jacs.5b00033. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Neely J. M.; Rovis T. Pyridine synthesis by [4 + 2] cycloadditions of 1-azadienes: hetero-Diels Alder and transition metal-catalysed approaches. Org. Chem. Front. 2014, 1, 1010–1015. 10.1039/c4qo00187g. [DOI] [Google Scholar]; c Reddy R. S.; Lagishetti C.; Chen S.; Kiran I. N. C.; He Y. Synthesis of Dihydrophenanthridines and Oxoimidazolidines from Anilines and Ethylglyoxylate via Aza Diels–Alder Reaction of Arynes and KF-Induced Annulation. Org. Lett. 2016, 18, 4546–4549. 10.1021/acs.orglett.6b02186. [DOI] [PubMed] [Google Scholar]; d Hatanaka Y.; Nantaku S.; Nishimura Y.; Otsuka T.; Sekikaw T. Catalytic enantioselective aza-Diels–Alder reactions of unactivated acyclic 1,3-dienes with aryl-, alkenyl-, and alkyl-substituted imines. Chem. Commun. 2017, 53, 8996–8999. 10.1039/c7cc03010j. [DOI] [PubMed] [Google Scholar]
a Bendale A. R.; Bhatt R.; Nagar A.; Jadhav A. G.; Vidyasagar G. Schiff base synthesis by unconventional route: an innovative green approach. Der. Pharma. Chemica. 2011, 3, 34–38. [Google Scholar]; b Kaupp G. Mechanochemistry: the varied applications of mechanical bond-breaking. CrystEngComm 2009, 11, 388–403. 10.1039/b810822f. [DOI] [Google Scholar]
a Barge M.; Salunkhe R. Aqueous extract of Balanites roxburghii fruit: a green dispersant for C-C bond formation. RSC Adv. 2014, 4, 31177–31183. 10.1039/c4ra04387a. [DOI] [Google Scholar]; b Pati H. N.; Das U.; Clercq E. D.; Balzarini J.; Dimmock J. R. Molecular modifications of 2-arylidene-1-indanones leading to increased cytotoxic potencies. J. Enzyme Inhib. Med. Chem. 2007, 22, 37–42. 10.1080/14756360600958057. [DOI] [PubMed] [Google Scholar]
Firouzeh N.; Hossein K. A Green and Highly Efficient Protocol for Catalyst-free Knoevenagel Condensation and Michael Addition of Aromatic Aldehydes with 1,3-Cyclic Diketones in PEG-400. Chin. J. Chem. 2011, 29, 2407–2410. 10.1002/cjoc.201100005. [DOI] [Google Scholar]; b Yu J.-J.; Wang L.-M.; Liu J.-Q.; Guo F.-L.; Liu Y.; Jiao N. Synthesis of tetraketones in water and under catalyst-free conditions. Green Chem. 2010, 12, 216–219. 10.1039/b913816a. [DOI] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

ao9b01960_si_001.pdf^{(9.6MB, pdf)}

ao9b01960_si_002.cif^{(13.5MB, cif)}

[ref1] a Zhang J.; El-Shabrawy A.-R. O.; El-Shanawany M. A.; Schiff P. L.; Slatkin D. J. New azafluorene alkaloids from Oxandra xylopioides. J. Nat. Prod. 1987, 50, 800–806. 10.1021/np50053a005. [DOI] [Google Scholar]; b Nugiel D. A.; Etzkorn A.-M.; Vidwans A.; Benfield P. A.; Boisclair M.; Burton C. R.; Cox S.; Czerniak P. M.; Doleniak D.; Seitz S. P. Indenopyrazoles as Novel Cyclin Dependent Kinase (CDK) Inhibitors. J. Med. Chem. 2001, 44, 1334–1336. 10.1021/jm0100032. [DOI] [PubMed] [Google Scholar]; c Frédérick R.; Dumont W.; Ooms F.; Aschenbach L.; Van der Schyf C. J.; Castagnoli N.; Wouters J.; Krief A. Synthesis, Structural Reassignment, and Biological Activity of Type B MAO Inhibitors Based on the 5H-Indeno[1,2-c]pyridazin-5-one Core. J. Med. Chem. 2006, 49, 3743–3747. 10.1021/jm051091j. [DOI] [PubMed] [Google Scholar]

[ref2] a Miri R.; Javidnia K.; Hemmateenejad B.; Azarpira A.; Amirghofran Z. Synthesis, cytotoxicity, QSAR, and intercalation study of new diindenopyridine derivatives. Bioorg. Med. Chem. 2004, 12, 2529–2536. 10.1016/j.bmc.2004.03.032. [DOI] [PubMed] [Google Scholar]; b Safak C.; Simsek R.; Altas Y.; Boydag S.; Erol K. 2-Methyl-3-acetyl-4-aryl-5-oxo-1,4-dihydro-5H-indeno (1,2-b) pyridine derivative studies and their calcium antagonistic activities. Boll. Chim. Farm. 1997, 136, 665–669. [PubMed] [Google Scholar]

[ref3] Nicolaou K. C.; Montagnon T.; Vassilikogiannakis G.; Mathison C. J. N. The Total Synthesis of Coleophomones B, C, and D. J. Am. Chem. Soc. 2005, 127, 8872–8888. 10.1021/ja0509984. [DOI] [PubMed] [Google Scholar]

[ref4] a Addla D.; Bhima; Sridhar B.; Devi A.; Kantevari S. Design, synthesis and antimicrobial evaluation of novel 1-benzyl 2-butyl-4-chloroimidazole embodied 4-azafluorenones via molecular hybridization approach. Bioorg. Med. Chem. Lett. 2012, 22, 7475–7480. 10.1016/j.bmcl.2012.10.042. [DOI] [PubMed] [Google Scholar]; b Chakrabarty S.; Croft M. S.; Marko M. G.; Moyna G. Synthesis and evaluation as potential anticancer agents of novel tetracyclic indenoquinoline derivatives. Bioorg. Med. Chem. 2013, 21, 1143–1149. 10.1016/j.bmc.2012.12.026. [DOI] [PubMed] [Google Scholar]; c Muscia G. C.; Buldain G. Y.; Asís S. E. Design, synthesis and evaluation of acridine and fused-quinoline derivatives as potential anti-tuberculosis agents. Eur. J. Med. Chem. 2014, 73, 243–249. 10.1016/j.ejmech.2013.12.013. [DOI] [PubMed] [Google Scholar]

[ref5] Nagarajan M.; Morrell A.; Fort B. C.; Meckley M. R.; Antony S.; Kohlhagen G.; Pommier Y.; Cushman M. Synthesis and anticancer activity of simplified indenoisoquinoline topoisomerase I inhibitors lacking substituents on the aromatic rings. J. Med. Chem. 2004, 47, 5651. 10.1021/jm040025z. [DOI] [PubMed] [Google Scholar]

[ref6] a Pizzirani D.; Roberti M.; Grimaudo S.; Di Cristina A.; Pipitone R. M.; Tolomeo M.; Recanatini M. Identification of Biphenyl-Based Hybrid Molecules Able To Decrease the Intracellular Level of Bcl-2 Protein in Bcl-2 Overexpressing Leukemia Cells. J. Med. Chem. 2009, 52, 6936–6940. 10.1021/jm900907s. [DOI] [PubMed] [Google Scholar]

[ref7] Wu X.; Li X.; Li Z.; Yu Y.; You Q.; Zhang X. Discovery of Nonquinone Substrates for NAD(P)H: Quinone Oxidoreductase 1 (NQO1) as Effective Intracellular ROS Generators for the Treatment of Drug-Resistant Non-Small-Cell Lung Cancer. J. Med. Chem. 2018, 61, 11280–11297. 10.1021/acs.jmedchem.8b01424. [DOI] [PubMed] [Google Scholar]

[ref8] a Huang H.-H.; Prabhakar C.; Tang K.-C.; Chou P.-T.; Huang G.-J.; Yang J.-S. Ortho-Branched Ladder-Type Oligophenylenes with Two-Dimensionally π-Conjugated Electronic Properties. J. Am. Chem. Soc. 2011, 133, 8028–8039. 10.1021/ja202144v. [DOI] [PubMed] [Google Scholar]; b Gómez-Esteban S.; Benito-Hernandez A.; Termine R.; Hennrich G.; Navarrete J. T. L.; Ruiz Delgado M. C.; Golemme A.; Gómez-Lor B. High-Mobility Self-Assembling Truxenone-Based n-Type Organic Semiconductors. Chem.—Eur. J. 2018, 24, 3576–3583. 10.1002/chem.201705760. [DOI] [PubMed] [Google Scholar]; c Sanguinet L.; Williams J. C.; Yang Z.; Twieg R. J.; Mao G.; Singer K. D.; Wiggers G.; Petschek R. G. Synthesis and Characterization of New Truxenones for Nonlinear Optical Applications. Chem. Mater. 2006, 18, 4259–4269. 10.1021/cm0601887. [DOI] [Google Scholar]; d Chaudhri N.; Grover N.; Sankar M. Nickel-Induced Skeletal Rearrangement of Free Base trans-Chlorins into Monofused NiII-Porphyrins: Synthesis, Structural, Spectral, and Electrochemical Redox Properties. Inorg. Chem. 2018, 57, 11349–11360. 10.1021/acs.inorgchem.8b00798. [DOI] [PubMed] [Google Scholar]; e Zatsikha Y. V.; Schrage B. R.; Meyer J.; Nemykin V. N.; Ziegler C. J. 1,3-Diylideneisoindolines: Synthesis, Structure, Redox, and Optical Properties. J. Org. Chem. 2019, 84, 6217–6222. 10.1021/acs.joc.9b00468. [DOI] [PubMed] [Google Scholar]

[ref9] a Vilches-Herrera M.; Knepper I.; de Souza N.; Villinger A.; Sosnovskikh V. Y.; Iaroshenko V. O. One-pot, three-component synthesis of 7-azaindole derivatives from N-substituted 2-amino-4-cyanopyrroles, various aldehydes, and active methylene compounds. ACS Comb. Sci. 2012, 14, 434–441. 10.1021/co300042v. [DOI] [PubMed] [Google Scholar]; b Khurana J. M.; Chaudhary A.; Nand B.; Lumb A. Aqua mediated indium(III) chloride catalyzed synthesis of fused pyrimidines and pyrazoles. Tetrahedron Lett. 2012, 53, 3018–3022. 10.1016/j.tetlet.2012.04.001. [DOI] [Google Scholar]; c Siddiqui Z. N.; Khan K. Friedlander synthesis of novel benzopyranopyridines in the presence of chitosan as heterogeneous, efficient and biodegradable catalyst under solvent-free conditions. New J. Chem. 2013, 37, 1595–1602. 10.1039/c3nj00069a. [DOI] [Google Scholar]; d Ray S.; Brown M.; Bhaumik A.; Dutta A.; Mukhopadhyay C. A new MCM-41 supported HPF6 catalyst for the library synthesis of highly substituted 1,4-dihydropyridines and oxidation to pyridines: report of one-dimensional packing towards LMSOMs and studies on their photophysical properties. Green Chem. 2013, 15, 1910–1924. 10.1039/c3gc40441b. [DOI] [Google Scholar]

[ref10] a Zhou Y.-J.; Chen D.-S.; Li Y.-L.; Liu Y.; Wang X.-S. Combinatorial Synthesis of Pyrrolo[3,2-f]quinoline and Pyrrolo[3,2-a]acridine Derivatives via a Three-Component Reaction under Catalyst-Free Conditions. ACS Comb. Sci. 2013, 15, 498–502. 10.1021/co400073m. [DOI] [PubMed] [Google Scholar]; b Chen M.; Sun N.; Liu Y. Environmentally benign synthesis of indeno[1,2-b]quinolines via an intramolecular Povarov reaction. Org. Lett. 2013, 15, 5574–5577. 10.1021/ol402775k. [DOI] [PubMed] [Google Scholar]; c Allais C.; Liéby-Muller F.; Rodriguez J.; Constantieux T. Metal-Free Michael-Addition-Initiated Three-Component Reaction for the Regioselective Synthesis of Highly Functionalized Pyridines: Scope, Mechanistic Investigations and Applications. Eur. J. Org. Chem. 2013, 4131–4145. 10.1002/ejoc.201300246. [DOI] [Google Scholar]; d Marquise N.; Dorcet V.; Chevallier F.; Mongin F. Synthesis of substituted azafluorenones from dihalogeno diaryl ketones by palladium-catalyzed auto-tandem processes. Org. Biomol. Chem. 2014, 12, 8138–8141. 10.1039/c4ob01629g. [DOI] [PubMed] [Google Scholar]; e Rao Y.; Liu M.; Wu L.; Yin G. Catalyst-free one-pot domino reactions for selective synthesis of functionalized 2,8-oxazabicyclo[3.3.1]-nonanes and 5H-indeno[1,2-b]pyridin-5-ones. RSC Adv. 2014, 4, 64551–64558. 10.1039/c4ra13166e. [DOI] [Google Scholar]

[ref11] a Tu S.-J.; Jiang B.; Zhang J.-Y.; Jia R.-H.; Zhang Y.; Yao C.-S. Efficient and direct synthesis of poly-substituted indeno[1,2-b]quinolines assisted by p-toluene sulfonic acid using high-temperature water and microwave heating via one-pot, three-component reaction. Org. Biomol. Chem. 2006, 4, 3980–3985. 10.1039/b611462h. [DOI] [PubMed] [Google Scholar]; b Majumder S.; Sharma M.; Bhuyan P. J. Microwave promoted diastereoselective synthesis of dihydroindeno[1,2-b]furans via one-pot three-component reaction in solvent-free conditions. Tetrahedron Lett. 2013, 54, 6868–6870. 10.1016/j.tetlet.2013.10.023. [DOI] [Google Scholar]; c Ahadi S.; Moafi L.; Feiz A.; Bazgir A. Three-component synthesis of new unsymmetrical oxindoles via Friedel-Crafts type reaction. Tetrahedron 2011, 67, 3954–3958. 10.1016/j.tet.2011.02.054. [DOI] [PMC free article] [PubMed] [Google Scholar]; d Liang B.; Kalidindi S.; Porco J. A.; Stephenson C. R. J. Multicomponent reaction discovery: three-component synthesis of spirooxindoles. Org. Lett. 2010, 12, 572–575. 10.1021/ol902764k. [DOI] [PMC free article] [PubMed] [Google Scholar]

[ref12] a Tu S.-J.; Jiang B.; Jia R.-H.; Zhang J.-Y.; Zhang Y.; Yao C.-S.; Shi F. An efficient one-pot, three-component synthesis of indeno[1,2-b]quinoline-9,11(6H,10H)-dione, acridine-1,8(2H,5H)-dione and quinoline-3-carbonitrile derivatives from enaminones. Org. Biomol. Chem. 2006, 4, 3664–3668. 10.1039/b607575d. [DOI] [PubMed] [Google Scholar]; b Ghahremanzadeh R.; Imani Shakibaei G.; Ahadi S.; Bazgir A. One-Pot, Pseudo Four-Component Synthesis of a Spiro[diindeno[1,2-b:2′,1′-e]pyridine-11,3′-indoline]-trione Library. J. Comb. Chem. 2010, 12, 191–194. 10.1021/cc900130a. [DOI] [PubMed] [Google Scholar]; c Ghahremanzadeh R.; Ahadi S.; Shakibaei G. I.; Bazgir A. Grindstone chemistry: one-pot synthesis of spiro[diindenopyridine-indoline]triones and spiro[acenaphthylene-diindenopyridine]triones. Tetrahedron Lett. 2010, 51, 499–502. 10.1016/j.tetlet.2009.11.041. [DOI] [Google Scholar]; d Mondal A.; Mukhopadhyay C. FeCl3-Catalyzed Combinatorial Synthesis of Functionalized Spiro[Indolo-3,10′-indeno [1,2-b]quinolin]-trione Derivatives. ACS Comb. Sci. 2015, 17, 404–408. 10.1021/acscombsci.5b00038. [DOI] [PubMed] [Google Scholar]; e Mondal A.; Banerjee B.; Bhaumik A.; Mukhopadhyay C. Activated Alumina Balls under Neat Conditions: A Green Catalyst for the Synthesis of Spiro-Heterocyclic Scaffolds by Ring-Opening versus Annulation of the Isatin Moiety. ChemCatChem 2016, 8, 1185–1198. 10.1002/cctc.201500885. [DOI] [Google Scholar]

[ref13] a Tugrak M.; Inci Gul H.; Sakagami H.; Gulcin I.; Supuran C. T. New azafluorenones with cytotoxic and carbonic anhydrase inhibitory properties: 2-Aryl-4-(4-hydroxyphenyl)-5H-indeno[1,2-b]pyridin-5-ones. Bioorg. Chem. 2018, 81, 433–439. 10.1016/j.bioorg.2018.09.013. [DOI] [PubMed] [Google Scholar]; b Jangra H.; Chen Q.; Fuks E.; Zenz I.; Mayer P.; Ofial A. R.; Zipse H.; Mayr H. Nucleophilicity and Electrophilicity Parameters for Predicting Absolute Rate Constants of Highly Asynchronous 1,3-Dipolar Cycloadditions of Aryldiazomethanes. J. Am. Chem. Soc. 2018, 140, 16758–16772. 10.1021/jacs.8b09995. [DOI] [PubMed] [Google Scholar]; c Chen Y.-R.; Ganapuram M. R.; Hsieh K.-H.; Chen K.-H.; Karanam P.; Vagh S. S.; Liou Y.-C.; Lin W. 3-Homoacyl coumarin: an all carbon 1,3-dipole for enantioselective concerted (3+2) cycloaddition. Chem. Commun. 2018, 54, 12702–12705. 10.1039/c8cc07271j. [DOI] [PubMed] [Google Scholar]; d Xu H.; Sha F.; Li Q.; Wu X.-Y. Catalytic asymmetric Tamura cycloaddition of homophthalic anhydrides with 2-arylidene-1,3-diones. Org. Biomol. Chem. 2018, 16, 7214–7222. 10.1039/c8ob01970c. [DOI] [PubMed] [Google Scholar]; e Xu H.; Chen K.; Liu H.-W.; Wang G.-W. Solvent-free N-iodosuccinimide-promoted synthesis of spiroimidazolines from alkenes and amidines under ball-milling conditions. Org. Chem. Front. 2018, 5, 2864–2869. 10.1039/c8qo00723c. [DOI] [Google Scholar]; f Hussein E. M.; Moussa Z.; Ahmed S. A. Exclusive regioselective 1,3-dipolar cycloaddition of 9-diazo-9H-fluorene and diphenyldiazomethane to 2-arylideneindane-1,3-diones: new approach toward effective synthesis of novel spiropyrazole derivatives. Monatsh. Chem. 2018, 149, 2021–2030. 10.1007/s00706-018-2249-0. [DOI] [Google Scholar]

[ref14] a Meena K.; Kumari S.; Khurana J. M.; Malik A. Efficient syntheses of novel indeno[1,2-b]chromenone derivatives via hetero-Diels-Alder reactions of 2-(arylmethylene)-1H-indene-1,3(2H)-diones with enaminones. Tetrahedron Lett. 2018, 59, 1493–1496. 10.1016/j.tetlet.2018.03.014. [DOI] [Google Scholar]; b Wang M.; Tang B.-C.; Xiang J.-C.; Cheng Y.; Wang Z.-X.; Ma J.-T.; Wu Y.-D.; Wu A.-X. C(sp3)-H Bond Functionalization of Benzo[c]oxepines via C-O bond Cleavage: Formal [3+3] Synthesis of Multisubstituted Chromans. J. Org. Chem. 2018, 83, 3409–3416. 10.1021/acs.joc.8b00126. [DOI] [PubMed] [Google Scholar]; c Qi J.; Zheng J.; Cui S. Facile synthesis of carbo- and heterocycles via Fe(III)-catalyzed alkene hydrofunctionalization. Org. Chem. Front. 2018, 5, 222–225. 10.1039/c7qo00817a. [DOI] [Google Scholar]; d Yu J.-K.; Chien H.-W.; Lin Y.-J.; Karanam P.; Chen Y.-H.; Lin W. Diversity-oriented synthesis of chromenopyrrolidines from azomethine ylides and 2-hydroxybenzylidene indandiones via base-controlled regiodivergent (3+2) cycloaddition. Chem. Commun. 2018, 54, 9921–9924. 10.1039/c8cc05693e. [DOI] [PubMed] [Google Scholar]; e Rapi Z.; Nemcsok T.; Grün A.; Pálvölgyi Á.; Samu G.; Hessz D.; Kubinyi M.; Kállay M.; Keglevich G.; Bakó P. Asymmetric cyclopropanation reactions catalyzed by carbohydrate-based crown ethers. Tetrahedron 2018, 74, 3512–3526. 10.1016/j.tet.2018.04.087. [DOI] [Google Scholar]

[ref15] a Yang S.-M.; Karanam P.; Wang M.; Jang Y.-J.; Yeh Y.-S.; Tseng P.-Y.; Ganapuram M. R.; Liou Y.-C.; Lin W. A vinylogous Michael addition-triggered quadruple cascade reaction for the enantioselective generation of multiple quaternary stereocenters,. Chem. Commun. 2019, 55, 1398–1401. 10.1039/c8cc09219b. [DOI] [PubMed] [Google Scholar]; b Solanke P.; Pytela O.; Bureš F.; Klikar M. T-shaped D-π-A-(π-A)2 chromophores with two auxiliary electron acceptors. Dyes Pigm. 2019, 162, 755–762. 10.1016/j.dyepig.2018.10.077. [DOI] [Google Scholar]; c Matsuo Y.; Yu C.-G.; Nakagawa T.; Okada H.; Ueno H.; Sun T.-G.; Zhong Y.-W. Reduced Knoevenagel Reaction of Acetetracenylene-1,2-dione with Acceptor Units for Luminescent Tetracene Derivatives. J. Org. Chem. 2019, 84, 2339–2345. 10.1021/acs.joc.8b03083. [DOI] [PubMed] [Google Scholar]

[ref16] a Baruah B.; Bhuyan P. J. Synthesis of some complex pyrano[2,3-b]- and pyrido[2,3-b]quinolines from simple acetanilides via intramolecular domino hetero Diels-Alder reactions of 1-oxa-1,3-butadienes in aqueous medium. Tetrahedron 2009, 65, 7099–7104. 10.1016/j.tet.2009.06.036. [DOI] [Google Scholar]; b Liu J.; Wang X.; Sun C.-L.; Li B.-J.; Shi Z.-J.; Wang M. New strategy to construct fused/bridged/spiro carbocyclic scaffolds based on the design of novel 6-C synthon precursor. Org. Biomol. Chem. 2011, 9, 1572–1577. 10.1039/c0ob00660b. [DOI] [PubMed] [Google Scholar]; c Xu H.; Sha F.; Li Q.; Wu X.-Y. Catalytic asymmetric Tamura cycloaddition of homophthalic anhydrides with 2-arylidene-1,3-diones. Org. Biomol. Chem. 2018, 16, 7214–7222. 10.1039/c8ob01970c. [DOI] [PubMed] [Google Scholar]

[ref17] a Bhuyan D.; Sarmah M. M.; Dommaraju Y.; Prajapati D. Microwave-promoted efficient synthesis of spiroindenotetrahydropyridine derivatives via a catalyst- and solvent-free pseudo one-pot five-component tandem Knoevenagel/aza-Diels-Alder reaction. Tetrahedron Lett. 2014, 55, 5133–5136. 10.1016/j.tetlet.2014.07.086. [DOI] [Google Scholar]; b Madhusudhan Reddy G.; Ko C. T.; Hsieh K. H.; Lee C. J.; Das U.; Lin W. W. Expanding the Scope of Primary Amine Catalysis: Stereoselective Synthesis of Indanedione-Fused 2,6-Disubstituted trans-Spirocyclohexanones. J. Org. Chem. 2016, 81, 2420–2431. 10.1021/acs.joc.5b02921. [DOI] [PubMed] [Google Scholar]; c Xi Q.-Z.; Gan Z.-J.; Li E.-Q.; Duan Z. Bronsted Acid Tuned, Lewis Base Promoted [4+2] Annulation Reactions of Allenoates with Electron-Deficient Olefins. Eur. J. Org. Chem. 2018, 4917–4925. 10.1002/ejoc.201800917. [DOI] [Google Scholar]

[ref19] Yang W.-J.; Sun Q.; Sun J.; Yan C.-G. Domino aza/oxa-hetero-Diels–Alder reaction for construction of novel spiro[pyrido[3′,2′:5,6]pyrano[2,3-d]pyrimidine-7,5′-pyrimidine]. Org. Chem. Front. 2018, 5, 2754–2758. 10.1039/c8qo00784e. [DOI] [Google Scholar]

[ref20] Gu R.; Flidrova K.; Lehn J.-M. Dynamic Covalent Metathesis in the C=C/C=N Exchange between Knoevenagel Compounds and Imines. J. Am. Chem. Soc. 2018, 140, 5560–5568. 10.1021/jacs.8b01849. [DOI] [PubMed] [Google Scholar]

[ref21] Domingo L. R.; Sáez J. A. Understanding the mechanism of polar Diels-Alder reactions. Org. Biomol. Chem. 2009, 7, 3576–3583. 10.1039/b909611f. [DOI] [PubMed] [Google Scholar]

[ref22] a Chu J. C. K.; Dalton D. M.; Rovis T. Zn-Catalyzed Enantio- and Diastereoselective Formal [4 + 2] Cycloaddition Involving Two Electron-Deficient Partners: Asymmetric Synthesis of Piperidines from 1-Azadienes and Nitro-Alkenes. J. Am. Chem. Soc. 2015, 137, 4445–4452. 10.1021/jacs.5b00033. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Neely J. M.; Rovis T. Pyridine synthesis by [4 + 2] cycloadditions of 1-azadienes: hetero-Diels Alder and transition metal-catalysed approaches. Org. Chem. Front. 2014, 1, 1010–1015. 10.1039/c4qo00187g. [DOI] [Google Scholar]; c Reddy R. S.; Lagishetti C.; Chen S.; Kiran I. N. C.; He Y. Synthesis of Dihydrophenanthridines and Oxoimidazolidines from Anilines and Ethylglyoxylate via Aza Diels–Alder Reaction of Arynes and KF-Induced Annulation. Org. Lett. 2016, 18, 4546–4549. 10.1021/acs.orglett.6b02186. [DOI] [PubMed] [Google Scholar]; d Hatanaka Y.; Nantaku S.; Nishimura Y.; Otsuka T.; Sekikaw T. Catalytic enantioselective aza-Diels–Alder reactions of unactivated acyclic 1,3-dienes with aryl-, alkenyl-, and alkyl-substituted imines. Chem. Commun. 2017, 53, 8996–8999. 10.1039/c7cc03010j. [DOI] [PubMed] [Google Scholar]

[ref23] a Bendale A. R.; Bhatt R.; Nagar A.; Jadhav A. G.; Vidyasagar G. Schiff base synthesis by unconventional route: an innovative green approach. Der. Pharma. Chemica. 2011, 3, 34–38. [Google Scholar]; b Kaupp G. Mechanochemistry: the varied applications of mechanical bond-breaking. CrystEngComm 2009, 11, 388–403. 10.1039/b810822f. [DOI] [Google Scholar]

[ref24] a Barge M.; Salunkhe R. Aqueous extract of Balanites roxburghii fruit: a green dispersant for C-C bond formation. RSC Adv. 2014, 4, 31177–31183. 10.1039/c4ra04387a. [DOI] [Google Scholar]; b Pati H. N.; Das U.; Clercq E. D.; Balzarini J.; Dimmock J. R. Molecular modifications of 2-arylidene-1-indanones leading to increased cytotoxic potencies. J. Enzyme Inhib. Med. Chem. 2007, 22, 37–42. 10.1080/14756360600958057. [DOI] [PubMed] [Google Scholar]

[ref25] Firouzeh N.; Hossein K. A Green and Highly Efficient Protocol for Catalyst-free Knoevenagel Condensation and Michael Addition of Aromatic Aldehydes with 1,3-Cyclic Diketones in PEG-400. Chin. J. Chem. 2011, 29, 2407–2410. 10.1002/cjoc.201100005. [DOI] [Google Scholar]; b Yu J.-J.; Wang L.-M.; Liu J.-Q.; Guo F.-L.; Liu Y.; Jiao N. Synthesis of tetraketones in water and under catalyst-free conditions. Green Chem. 2010, 12, 216–219. 10.1039/b913816a. [DOI] [Google Scholar]

PERMALINK

Construction of Dispiro-Indenone Scaffolds via Domino Cycloaddition Reactions of α,β-Unsaturated Aldimines with 2-Arylidene-1,3-indenediones and 2,2′-(Arylmethylene)bis(1,3-indenediones)

Wen-Juan Yang

Hui-Lin Fang

Jing Sun

Chao-Guo Yan

Abstract

1. Introduction

Figure 1.

2. Results and Discussion

Table 1. Optimizing Reaction Conditionsa.

Table 2. Synthesis of Spiropolycycles 3a–3v via the Aza/Oxa-Diels–Alder Reactiona.

Figure 2.

Table 3. Synthesis of Spiropolycycles 4a–4r via the Aza/Oxa-Diels–Alder Reactiona.

Figure 3.

Scheme 1. Proposed Concerted Reaction Mechanism.

Table 4. Synthesis of Dispirocyclohexanes 5a–5n via the Domino Cyclization Reactiona.

Scheme 2. Illustration of the Two Main Isomers of Dispiro Compounds.

Figure 4.

Scheme 3. Plausible Formation Mechanism for Dispiro Compound 5.

3. Conclusions

4. Experimental Section

4.1. General Information

4.2. General Procedure for the Synthesis of Polycyclic Compounds 3a–3v

4.3. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(4-bromophenyl)-1′-(4-methoxyphenyl)-4′-(p-tolyl)-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3a)

4.4. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(4-bromophenyl)-1′,4′-bis(4-methoxyphenyl)-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3b)

4.5. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(4-bromophenyl)-4′-(4-fluorophenyl)-1′-(4-methoxyphenyl)-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3c)

4.6. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(4-bromophenyl)-1′-(4-methoxyphenyl)-4′-(4-nitrophenyl)-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3d)

4.7. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(4-bromophenyl)-1′,4′-diphenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3e)

4.8. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(4-bromophenyl)-1′-(4-methoxyphenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3f)

4.9. (2′S,4′R,4a′S,5′S,11a′S)-1′,2′,5′-Tris(4-bromophenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3g)

4.10. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(4-nitrophenyl)-1′,4′-diphenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3h)

4.11. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Methoxyphenyl)-2′,5′-bis(4-nitrophenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3i)

4.12. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Bromophenyl)-2′,5′-bis(4-nitrophenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3j)

4.13. (2′R,4′R,4a′R,5′R,11a′S)-2′,5′-Bis(2-chlorophenyl)-1′-(4-methoxyphenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3k)

4.14. (2′R,4′R,4a′R,5′R,11a′S)-2′,5′-Bis(2-bromophenyl)-4′-phenyl-1′-(p-tolyl)-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3l)

4.15. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(3-chlorophenyl)-1′,4′-diphenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3m)

4.16. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(3-chlorophenyl)-1′-(4-methoxyphenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3n)

4.17. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Bromophenyl)-2′,5′-bis(3-chlorophenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3o)

4.18. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(3-fluorophenyl)-1′,4′-diphenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3p)

4.19. (2′S,4′R,4a′S,5′S,11a′S)-1′,2′,4′,5′-Tetraphenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3q)

4.20. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Methoxyphenyl)-2′,4′,5′-triphenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3r)

4.21. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Bromophenyl)-2′,4′,5′-triphenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3s)

4.22. (2′S,4′R,4a′S,5′S,11a′S)-1′,4′-Diphenyl-2′,5′-di-p-tolyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3t)

4.23. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Methoxyphenyl)-4′-phenyl-2′,5′-di-p-tolyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3u)

4.24. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Bromophenyl)-4′-phenyl-2′,5′-di-p-tolyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (3v)

4.25. 2-(3-(4-Methoxyphenyl)allylidene)-1H-indene-1,3(2H)-dione

4.26. General Procedure for the Synthesis of Polycyclic Compounds 4a–4r

4.27. (2′S,4′R,4a′S,5′S,11a′S)-1′-Benzyl-2′,4′,5′-triphenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4a)

4.28. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Chlorobenzyl)-2′,4′,5′-triphenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4b)

4.29. (2′S,4′R,4a′S,5′S,11a′S)-1′-Benzyl-2′,5′-bis(4-chlorophenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4c)

4.30. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(4-chlorophenyl)-1′-(4-methoxybenzyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4d)

4.31. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Chlorobenzyl)-2′,5′-bis(4-chlorophenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4e)

4.32. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Bromobenzyl)-2′,5′-bis(4-chlorophenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4f)

4.33. (2′S,4′R,4a′S,5′S,11a′S)-1′-Benzyl-2′,4′,5′-tris(4-chlorophenyl)-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4g)

4.34. (2′S,4′R,4a′S,5′S,11a′S)-1′-Benzyl-2′,5′-bis(4-chlorophenyl)-4′-(4-methoxyphenyl)-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4h)

4.35. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(3-fluorophenyl)-1′-(4-methylbenzyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4i)

4.36. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(3-fluorophenyl)-1′-(4-methoxybenzyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4j)

4.37. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Chlorobenzyl)-2′,5′-bis(3-fluorophenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4k)

4.38. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Bromobenzyl)-2′,5′-bis(3-fluorophenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4l)

4.39. (2′S,4′R,4a′S,5′S,11a′S)-1′-Benzyl-2′,5′-bis(4-bromophenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4m)

4.40. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Methylbenzyl)-4′-phenyl-2′,5′-di-p-tolyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4n)

4.41. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Chlorobenzyl)-4′-phenyl-2′,5′-di-p-tolyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4o)

4.42. (2′S,4′R,4a′S,5′S,11a′S)-1′-(4-Chlorobenzyl)-4′-phenyl-2′,5′-di-m-tolyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4p)

4.43. (2′S,4′R,4a′S,5′S,11a′S)-1′-Butyl-2′,5′-bis(3-fluorophenyl)-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4q)

4.44. (2′S,4′R,4a′S,5′S,11a′S)-2′,5′-Bis(4-bromophenyl)-1′-butyl-4′-phenyl-1′,4a′,5′,11a′-tetrahydro-2′H-spiro[indene-2,3′-indeno[2′,1′:5,6]pyrano[2,3-b]pyridine]-1,3,6′(4′H)-trione (4r)

4.45. General Procedure for the Synthesis of Dispiro Compounds 5a–5m

4.46. 2′,4′-Diphenyl-6′-(phenylamino)dispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraone (5a)

4.47. 4′-Phenyl-6′-(phenylamino)-2′-(p-tolyl)dispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraone (5b)

4.48. 2′-(2-Fluorophenyl)-4′-phenyl-6′-(phenylamino)dispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraone (5c)

4.49. 4′-((3-Chlorophenyl)amino)-2′-(2-fluorophenyl)-6′-phenyldispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraone (5d)

4.50. 2′-(2-Chlorophenyl)-4′-phenyl-6′-(phenylamino)dispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraone (5e)

4.51. 2′-(2-Chlorophenyl)-4′-((3-chlorophenyl)amino)-6′-phenyldispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraone (5f)

4.52. 2′-(2-Chlorophenyl)-4′-((4-methoxyphenyl)amino)-6′-phenyldispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraone (5g)

4.53. 2′-(4-Bromophenyl)-4′-phenyl-6′-(phenylamino)dispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraone (5h)

4.54. 2′-(2-Bromophenyl)-4′-phenyl-6′-(phenylamino)dispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraone (5i)

4.55. 2′-(2-Bromophenyl)-4′-phenyl-6′-(p-tolylamino)dispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraone (5j)

4.56. 2′-(2-Bromophenyl)-4′-((4-methoxyphenyl)amino)-6′-phenyldispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraone (5k)

4.57. 2′-(2-Bromophenyl)-4′-((4-methoxyphenyl)amino)-6′-(p-tolyl)dispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraone (5l)

4.58. 2′-(2-Bromophenyl)-4′-(4-methoxyphenyl)-6′-((4-methoxyphenyl)amino)dispiro[indene-2,1′-cyclohexane-3′,2″-indene]-1,1″,3,3″-tetraone (5m)

Table 1. Optimizing Reaction Conditions^a.

Table 2. Synthesis of Spiropolycycles 3a–3v via the Aza/Oxa-Diels–Alder Reaction^a.

Table 3. Synthesis of Spiropolycycles 4a–4r via the Aza/Oxa-Diels–Alder Reaction^a.

Table 4. Synthesis of Dispirocyclohexanes 5a–5n via the Domino Cyclization Reaction^a.