Synthesis and solid-state fluorescence properties of pentacyclic 7-substituted-indeno[1′,2′:4,5]pyrido[2,1-a]isoindol-5-ones

Abstract

With the aim to design fluorescent solids, a series of indeno[1′,2′:4,5]pyrido[2,1-a]isoindol-5-ones with various substituents was prepared. In these π-extended pentacyclic derivatives, the presence of a methyl group in the 7-position was found to have a critical influence on the fluorescence properties in the solid state. Crystal packing of the non-substituted derivatives shows strong π–π interactions causing quenching of the fluorescence. In contrast, by introducing a methyl substituent in the 7-position we obtained compounds with fluorescence quantum yield up to 32% in the solid state.

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Introduction

Solid-state organic luminescent compounds^1,2 have received considerable attention for practical use in organic electroluminescence devices (OLED),³ solid-state dye laser⁴ and sensors.⁵ Only a few compounds exhibit strong fluorescence both in solution and in the solid state because most of them undergo fluorescence quenching in aggregation state. Indeed, strong intermolecular interactions between neighbouring fluorophores generally lead to fluorescence quenching in the solid state.⁶

We have recently described the synthesis of N-containing pentacyclic compounds via a cascade reaction between 2,5-dihalopyridines and 2-formylbenzeneboronic acids.⁷ Most of the compounds exhibited excellent fluorescence properties in solution,⁸ but not in the solid state. However, compounds 1 and 2 bearing a methyl group in 7-position (Fig. 1) were identified as fluorescent solids. Introduction of a methyl substituent in 7-position could prevent strong intermolecular packing through π⋯π interactions in the solid state thus avoiding quenching of the fluorescence. In the non-substituted pentacycles (for instance 3 and 4), the fluorescence is quenched as a result of strong π⋯π stacking interactions in such extended π-conjugated systems.⁷ Based on these preliminary observations, we report herein the preparation and the photophysical study of new derivatives bearing a methyl or aryl substituent in 7-position. The fluorescence measurements confirm that all compounds with a methyl group in 7-position possess high quantum yields of fluorescence in the solid state whereas they are low in case of the aryl substituted compounds. The crystal structures of selected compounds were analysed in order to investigate the influence of the crystal packing on the fluorescence properties.

Fig. 1 Fluorescent pentacyclic compounds.

Results and discussion

Synthesis

Pentacyclic compounds bearing an electron-donating substituent (OCH₃) were prepared starting from pyridine 5 (Scheme 1). The cascade reaction of 5 with 3 eq. of boronic acid 6b yielded 7b. Alternatively, the reaction of 5 with one eq. of 2-formylbenzeneboronic acid 6a furnished intermediate 8 in moderate yield along with pentacycle 1 which formation was initiated in situ by a competitive second Suzuki coupling. Next, the reaction of 8 with 1.5 eq. of 6b gave pentacycle 9b having one methoxy substituent. Compounds 7b and 9b represent the analogues with a methyl substituent in 7-position of 7a and 9a, respectively (see Fig. 2 for the structures of 7a and 9a).

Scheme 1 Synthesis of pentacycles 7b and 9b.

Fig. 2 Overview of the pentacyclic compounds.

In order to extend the family of 7-substituted pentacycles, it was necessary to access to new 2-chloro-5-bromo-pyridines (Scheme 3) bearing a substituent in 6-position. For this purpose, the trihalopyridine substrate 11 was chosen as the key compound since it could allow a selective cross-coupling in 6-position. Pyridine 11 was prepared from 2-amino-6-bromo-pyridine 12 in two steps with an overall good yield.

Electrophilic bromination of 12 furnished the dibromoaminopyridine 13,⁹ followed by the replacement of the amino group by a chlorine through a Sandmeyer-type reaction to give 11 (Scheme 2). The cross-coupling of 11 in 6-position was performed with 1 eq. of various boronic acids to deliver the expected 2-chloro-5-bromo-6-arylpyridines 10a–e in good yields. Little change of the procedure allowed obtaining the pyridine-substituted derivative 10f in good yield. The Sonogashira coupling of 11 with a slight excess of phenylacetylene performed also smoothly to give 14 in good yield (Scheme 3).

Scheme 2 Synthesis of trihalopyridine 11.

Scheme 3 Synthesis of 6-substituted 2-chloro-5-bromopyridines.

Pyridine 10a was then reacted with 2.5 eq. of 2-formylphenylboronic acid 6a under standard conditions to give the expected pentacycle 15a in low yield and a large amount of non-cyclized bis-aldehyde 16. Obviously the presence of the bulky phenyl group reduced the pyridine nitrogen reactivity toward the aldehyde^10,11 thus increasing the stability of 16.¹² Moreover, when bis-aldehyde 16 was subjected to the same reaction conditions, pentacycle 15a was formed in good yield. When the catalyst was omitted the pentacycle was still formed although in a lower yield of 20% because of the important formation of degradation products (Scheme 4).

Scheme 4 Synthesis of pentacycle 15a under standard conditions.

Nevertheless, these experiments suggest that a more robust palladium catalyst could allow performing the cascade reaction in a single step. The bulky monophosphine ligand such as XPhos (2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl) has shown high performances in Suzuki coupling¹³ and other palladium-catalyzed reactions.¹⁴ The cascade reaction was then performed with catalytic system [Pd(OAc)₂, XPhos] and it was noticed that 5 eq. of 2-formylphenylboronic acid 6a were needed for the reaction to go to completion (Scheme 5). Under these conditions, the yield for pentacycle 15a could be increased to 53%. Pyridines 10b–d reacted smoothly to give compounds 15b–d in good yields whereas a moderate yield for 15f was obtained with bipyridine 10f. Complex mixtures were obtained after the reaction of substrates 10e and 14. As for pentacycle 1,⁷ the relative syn configuration was confirmed for compounds 2, 15a and 15d by XRD and was applied to the other compounds of the series 15b–c and 15f (vide infra).§

Scheme 5 Cascade reaction of 6-substituted pyridines 10 and 14.

To summarize, the structures of all the compounds considered in this study are depicted in Fig. 2.

Photophysical properties

In CH₂Cl₂ solution. The photophysical properties of compounds 1–4 are very similar: as an example, the absorption and emission spectra of 2 are reported as solid black lines in Fig. 3 and 4, respectively. Compounds 1–4 display the same lowest-energy absorption band, a bright emission at ca. 500 nm, with an intensity decay of few ns, insensitive to the presence of dioxygen in solution (Table 1), thus pointing to a fluorescent excited state. These results demonstrate that the presence of the methyl substituents in position 7 and/or 13 does not significantly affect the optical properties in solution.

Fig. 3 Absorption spectra of compounds 2 (solid black line), 7b (dashed gray line), 9b (dashed dotted black line) and 15a (dashed dotted dotted gray line) in CH₂Cl₂ solution.

Fig. 4 Normalized emission spectra of compounds 2 (solid black line), 7b (dashed gray line), 9b (dashed dotted black line) and 15a (dashed dotted dotted gray line) in CH₂Cl₂ solution. λ_ex = 400 nm.

Table 1 Most relevant photophysical data for all the compounds in air-equilibrated CH₂Cl₂ solution and in solid state at 298 K

	Absorption		Emission^a
	CH2Cl2		CH2Cl2			Solid
	λ (nm)	ε (M^−1 cm^−1)	λmax (nm)	τ (ns)	Φem^a	λ (nm)	Φem
a Fluorescence quantum yields in solution were measured using as standard perylene in air equilibrated EtOH solution (Φem = 0.92) and in solid state by an integrating sphere (see Experimental section).b No emission detected in the solid state.c These data are not reported because the sample is not fully stable in solution.d Data not available.
1	421	22 000	500	4.60	0.67	520	0.31
2	425	17 000	512	5.27	0.77	531	0.29
3	423	18 000	497	4.30	0.62	—^b	—^b
4	424	—^c	505	—^c	0.71	—^b	—^b
7a	430	18 000	518	0.7	0.11	—^d	—^d
7b	432	20 000	523	0.47	0.07	549	0.32
9a	422	17 000	498	5.10	0.78	—^d	—^d
9b	423	21 000	501	5.05	0.79	544	0.21
15a	423	16 700	502	4.88	0.74	552	0.09
15b	422	16 200	502	4.60	0.67	569	0.06
15c	421	16 700	501	4.79	0.62	586	0.08
15d	422	16 500	503	5.27	0.77	517	0.07
15f	421	17 900	501	5.33	0.73	557	0.06

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Upon appending one (9b) or two methoxy units (7b) at the external phenyl rings, a new band at ca. 330 nm arises in the absorption spectra and it can be attributed to electronic transitions of the methoxybenzene units. The emission spectrum of 9b is similar to the previously discussed spectrum of 2 (Fig. 3) with a remarkably high emission quantum yield (Table 1). On the other hand, compound 7b displays a weak emission band with no vibronic structure, a red-shifted maximum and a shorter lifetime. The photophysical properties of compounds 7b and 9b are very similar, in terms of energy, lifetime and emission quantum yield, to the corresponding previously investigated analogues 7a and 9a lacking the methyl substituent in position 7 (Fig. 2).⁸ This experimental finding points to the fact that the methyl substituent in that position does not affect the electronic properties of the chromophores in solution.

Compounds 15a–d and 15f have the same photophysical properties and the absorption (Fig. 3) and emission spectra (Fig. 4) of compound 15a, reported as a representative example, are very similar also from a quantitative point of view (Table 1) to those of compound 1.

In solid state. As previously discussed, highly luminescent organic molecules in solution are often not emissive in the solid state. We thus decided to investigate the emission spectra and the emission quantum yield in the solid state of all the above reported compounds. Compounds 3 and 4, as well as compounds 15a–d and 15f, which are all strongly emissive in CH₂Cl₂ solution, are either completely quenched or poorly emissive as a powder (Table 1). On the contrary, compounds 1, 2, 7b and 9b display a strong emission (Φ_em ca. 30%) in the solid state. The emission spectra in the solid state of two representative examples (1 and 15a) are reported in Fig. 5.

Fig. 5 Emission spectra of compounds 1 (gray line) and 15a (black line) as a powder. λ_ex = 400 nm. These spectra are not corrected for the reabsorption of the emitted light.

It is worth noting that compound 7b is poorly emissive in solution. Indeed, based on the previous investigation,⁸ for the lower emitting compounds the fluorescent excited state is mainly deactivated by non radiative pathways which are strongly inhibited in rigid environment (as in the solid state or in film): this may explain the strong increase of emission quantum yield in the case of 7b.

The discussed emission properties in the solid state are not a function of the degree of crystallinity, as demonstrated by comparing the emission quantum yields measured for powder samples and drop-cast solutions on glass slides.

To sum up these results, we can conclude that: (i) compounds with a methyl substituent in position 7 are the most emissive in solid, (ii) lower emission intensities are displayed by the phenyl substituted compounds, (iii) while compounds 3 and 4 bearing no substituent are not emissive. Therefore, the presence of a methyl or phenyl substituent in position 7 does strongly affect the emissive properties in the solid state, but not in solution (see above).

X-ray diffraction analysis

Crystal structures were determined by single crystal X-ray diffraction for compounds 2, 15a and 15d; the structures of 1, 4 and 7a were published in a previous article.⁷ In all investigated structures, the OH and R¹ group in 7-position are in syn conformation. Moreover, in 15a and 15d the same molecular synthons formed by O, C–H⋯O hydrogen bonding are observed (Fig. 6). These synthons are built from four molecules around an inversion center in 15a, and about a pseudo inversion center in the non-centrosymmetric structure of 15d; in this latter structure, the loss of inversion symmetry is induced by the ordering of the dichloromethane solvent molecules that are cocrystallised together with the pentacyclic compound. A similar molecular arrangement was also found in 3,10-dimethoxy related pentacycle 7a but not in 4 and 1–2.⁷ The molecular packing in 15a presents π⋯π interactions involving the pentacyclic backbone by its concave side (3.59 Å) and the phenyl group in 7-position (3.42 Å) separately.

Fig. 6 Molecular synthon about inversion center (left part of the figure) formed by O, C–H⋯O hydrogen bonds and π⋯π interactions (displayed as black lines) in 15a. Hydrogen atoms not involved in intermolecular bonding are omitted for clarity.

On the contrary, in 15d π⋯π interactions couple together p-CHO–C₆H₄ groups and pentacyclic backbones by their concave side (3.67 Å).

These packing are noticeably different from the one displayed by other related compounds. In the case of 4, the presence of the H atom in 7-position induces strong molecular packing through C–H⋯N hydrogen bond (H⋯N = 2.55 Å; C–H⋯N = 164.9°) and π⋯π interactions (3.67 Å) involving the whole pentacyclic backbone, through its concave and convex sides (Fig. 7a). The molecular packing is also different in the case of 1 where it is driven by multiple C–H⋯O, π hydrogen bonds and contacts with no π⋯π interactions (Fig. 7b). As what is observed for 15a, 2 presents π⋯π interactions involving the pentacyclic backbone by it concave side (3.42 Å) but cannot display the additional stacking interactions observed in 15a due to the non-aromatic nature of the R¹ (methyl) group (Fig. 8).

Fig. 7 Molecular packing of (a) 4, showing the strong π⋯π interaction involving the whole pentacyclic backbone together with the C–H⋯N, O hydrogen bond (displayed as black lines) and of (b) 1 hydrogen atoms not involved in hydrogen bonding are omitted for clarity.

Fig. 8 Molecular packing of 2, showing the π⋯π interaction involving the concave side of the pentacycle; the methyl group precludes such interaction from the convex side of the molecule.

Correlating these structural features to the photophysical properties shows that intermolecular π⋯π interactions are detrimental to fluorescence in the solid state. Indeed, with strong π⋯π overlap as in 4 involving both side of the molecule, no fluorescence is observed in the solid state despite of a good quantum yield in solution, while a small solid state quantum yield is obtained when this overlap is reduced (15a and 15d). In these last compounds, hydrogen bonding can also participate to the fluorescence quenching by bringing the molecules in close proximity one to each other. The highest yield is obtained for the crystal structure displaying no π⋯π interactions (1) or with only the concave side of the molecule (2), where the quantum yield is only halved going from solution to solid state.

Conclusions

We have succeeded in designing fluorescent solids by slight structural modification of the pentacyclic framework of indeno[1′,2′:4,5]pyrido[2,1-a]isoindol-5-ones. Indeed, the original pentacyclic compounds exhibited high fluorescence in solution but led to non-fluorescent solids due to π–π interactions which maintained the molecules in close proximity thus leading to fluorescence quenching. The introduction of a methyl group on the central pyridine ring close to the nitrogen (7-position) induced weaker π–π interactions and increased fluorescence in the solid state. Aryl groups on the same 7-position did not have the same improving effect on the solid state fluorescence due to additional π–π interactions between the added aryl groups.

Experimental

General remarks

Toluene and dioxane were distilled over sodium/benzophenone and stored over sodium. All other solvents and reagents were used as received. TLC was performed on silica gel plates and visualized with a UV lamp (254 nm). Chromatography was performed on silica gel (70–230 mesh). Melting points were measured on a Totoli apparatus. Proton and carbon NMR spectra were recorded on Bruker AC-200, AC-250 or AM-400 Fourier transform spectrometers using an internal deuterium lock. Chemical shifts are quoted in parts per million (ppm) downfield of tetramethylsilane. Coupling constants J are quoted in Hz. Mass spectra with electronic impact (MS-EI) were recorded from a Shimadzu QP 2010 apparatus. High resolution mass spectra were recorded from a Brucker micrOTOFQ (APCI-TOF).

Photophysical measurements

UV-Vis absorption spectra were recorded in solution with quartz cuvettes (optical pathlength 1 cm and 5 cm, Hellma®) by using a Perkin Elmer λ650 spectrophotometer. Corrected fluorescence emissions, excitation spectra and emission lifetimes were recorded in solution with an Edinburgh FLS920 spectrofluorimeter equipped with Hamamatsu H5773-04 phototube and a TCC900 card for data acquisition in time-correlated single-photon counting experiments (22 ps time resolution) by using a continuous 450 W Xenon arc lamp or a PicoQuant LDH-P-C-405 pulsed diode laser as excitation source. Fluorescence quantum yields were measured following the method of Demas and Crosby¹⁵ (standard used: perylene in air equilibrated EtOH solution, Φ_em = 0.92).¹⁶ Solid emission spectra and solid emission quantum yields were measured by an Edinburgh FLS920 spectrofluorimeter equipped with a barium sulfate coated integrating sphere (LabSphere, 4P-GPS-040-SF), a continuous 450 W Xenon arc lamp as light source and a Hamamatsu H5773-04 phototube, following the procedure described by De Mello et al.¹⁷ The experimental errors are within: ±2 nm of the band maximum, 5% of the molar absorption coefficient, 10% of the lifetime measurements, and 15% of the emission quantum yield in solid.

Single crystal X-ray diffraction

Single crystals were obtained by slow evaporation from dichloromethane solutions. Diffraction experiments were performed on a SuperNova CCD diffractometer (Agilent Technologies) using the CuKα radiation (λ = 1.5418 Å) for 2, 15a and 15d. Data collections under dinitrogen stream were obtained at 100 K for 15a and 110 K for 2 and 15d, respectively. The structures were solved by direct methods with the program SIR-92 ¹⁸ and full matrix least-square refinements on F2 in SHELX-97 ¹⁹ were performed with anisotropic displacements for non-H atoms. Hydrogen atoms were located in difference Fourier maps and refined isotropically according to the riding model.

3,10-Dimethoxy-7,8-dihydro-8-hydroxy-7-methyl-indeno[1′,2′:4,5]pyrido[2,1-a]isoindol-5-one (7b)

To a degassed toluene solution (12 mL) containing Pd(PPh₃)₄ (116 mg, 0.1 mmol) and pyridine 5 (206.5 mg, 1 mmol), degassed solution of boronic acid 6b (3 mmol) in methanol (3 mL) and aqueous solution (4 mL) of Na₂CO₃ (636 mg, 6 mmol) and NaBr (103 mg, 1 mmol) were successively added. After heating for 12 h at 100 °C, the reaction mixture was cooled to room temperature, extracted with ethyl acetate (3 × 20 mL) and dried over anhydrous magnesium sulphate (MgSO₄). After filtration on Celite and concentration, the residue was purified by chromatography on silica gel (cyclohexane/ethyl acetate) to give compound 7b (150 mg, 42%); mp 152–154 °C; ¹HNMR (CDCl₃, 200 MHz) δ 7.58 (d, J = 8.4 Hz, 1H), 7.40 (d, J = 8.4 Hz, 1H), 7.29 (d, J = 2.3 Hz, 1H), 7.10–7.17 (m, 2H), 6.89 (ddd, J = 8.4, 2.3, 0.6 Hz, 1H), 6.37 (d, J = 6.3 Hz, 1H), 6.19 (d, J = 6.3 Hz, 1H), 5.51 (s, 1H, OH), 5.34 (d, J = 0.6 Hz, 1H), 3.89 (s, 3H, OCH₃), 3.87 (s, 3H, OCH₃), 1.25 ppm (s, 3H, CH₃); ¹³CNMR (CDCl₃, 50 MHz) δ 169.7, 161.3, 160.8, 145.4, 141.8, 132.3, 129.6, 128.4, 128.35, 122.5, 121.4, 120.6, 116.6, 110.2, 108.6, 105.6, 103.0, 79.7, 67.7, 55.8, 55.6, 17.5 ppm. HRMS m/z calcd for C₂₂H₁₉NNaO₄ (M + Na): 384.1206, found: 384.1206.

2-(6-Chloro-2-methyl-pyridin-3-yl)-benzaldehyde (8)

To a degassed toluene solution (15 mL) containing Pd(PPh₃)₄ (173 mg, 0.15 mmol) and pyridine 5 (620 mg, 3 mmol) were successively added degassed solutions of 2-formylbenzeneboronic acid 6a (450 mg, 3 mmol) in methanol (6 mL) and Na₂CO₃ (636 mg, 6 mmol) in water (6 mL). After heating for 12 h at 100 °C, the reaction mixture was cooled to room temperature, extracted with ethyl acetate and dried over MgSO₄. After concentration, the residue was purified by chromatography on silica gel (cyclohexane/ethyl acetate) to give 8 (320 mg, 46%). Mp 88–90 °C; ¹HNMR (CDCl₃, 200 MHz) δ 9.81 (s, 1H, CHO), 8.04 (dd, J = 7.5, 1.3 Hz, 1H), 7.70 (dt, J = 7.5, 1.3 Hz, 1H), 7.59 (dt, J = 7.6, 1.4 Hz, 1H), 7.47 (d, J = 8.2 Hz, 1H), 7.28 (d, J = 8.2 Hz, 2H), 2.31 ppm (s, 3H, CH₃); ¹³CNMR (CDCl₃, 50 MHz) δ 190.9, 157.2, 150.2, 141.2, 140.0, 134.1, 133.7, 132.0, 130.7, 129.0, 128.8, 121.2, 22.9 ppm. MS (70 eV): m/z (%) 231 (M⁺, 100), 216 (58), 202 (33), 166 (33); HRMS m/z calcd for C₁₃H₁₁ClNO (M + H): 232.0524, found: 232.0532.

3-Methoxy-7,8-dihydro-8-hydroxy-7-methyl-indeno[1′,2′:4,5]pyrido[2,1-a]isoindol-5-one (9b)

To a degassed toluene solution (2 mL) containing Pd(PPh₃)₄ (25 mg, 0.022 mmol) and pyridine 8 (50 mg, 0.216 mmol) were successively added degassed solution of boronic acid 6b (58 mg, 0.324 mmol) in methanol (1 mL) and aqueous solution (1 mL) of Na₂CO₃ (69 mg, 0.648 mmol) and NaBr (22.3 mg, 0.216 mmol). After heating for 12 h at 100 °C, the reaction mixture was cooled to room temperature, extracted with ethyl acetate and dried over MgSO₄. After concentration, the residue was purified by chromatography on silica gel (cyclohexane/ethyl acetate) to give 9b (34 mg, 48%). Mp 132–134 °C; ¹HNMR (CDCl₃, 400 MHz) δ 7.61 (d, J = 6.4 Hz, 1H), 7.58 (d, J = 8.4 Hz, 1H), 7.48 (d, J = 6.4 Hz, 1H), 7.37 (dt, J = 7.2, 1.2 Hz, 1H), 7.33 (t, J = 6.4 HZ, 1H), 7.30 (d, J = 2.0 Hz, 1H), 7.14 (dd, J = 8.4, 2.4 Hz, 1H), 6.50 (d, J = 6.2 Hz, 1H), 6.18 (d, J = 6.2 Hz, 1H), 5.55 (br s, 1H, OH), 5.23 (d, J = 2.0 Hz, 1H), 3.89 (s, 3H, OCH₃), 1.25 (s, 3H, CH₃); ¹³CNMR (CDCl₃, 100 MHz) δ 169.7, 161.0, 143.2, 141.8, 135.8, 133.4, 129.8, 129.4, 128.5, 128.2, 125.0, 121.6, 121.1, 120.6, 112.4, 105.8, 102.4, 79.8, 67.6, 55.8, 17.4 ppm. HRMS m/z calcd for C₂₁H₁₇NNaO₃ (M + Na): 354.1111, found: 354.1101.

2-Amino-5,6-bromopyridine (13)

To a solution of 6-amino-2-bromopyridine 12 (3.46 g, 20 mmol) in DMF (100 mL) was added NBS (3.56 g, 20 mmol). The solution was stirred at room temperature for 6 h. The progress of the reaction was monitored by TLC. After disappearance of starting material, the mixture was poured into 200 mL of cold water. The product precipitated immediately. After filtration and drying, 13 was obtained as a white powder (4 g, 80%). Mp 149–151 °C; ¹H NMR (CDCl₃, 200 MHz) δ 4.65 (s, 2H, NH₂), 6.37 (d, J = 8.5 Hz, 2H), 7.56 ppm (d, J = 8.5 Hz, 1H); ¹³CNMR (CDCl₃, 50 MHz) δ 156.7, 142.6, 140.9, 109.5, 108.6 ppm. MS (70 eV): m/z (%) 252 (M⁺, 100), 171 (42), 92 (65), 64 (40), 41 (42); HRMS m/z calcd for C₅H₅Br₂N₂: 250.8814 (M + H), found: 250.8810.

2,3-Dibromo-6-chloropyridine (11)

To a solution of 2-amino-5,6-bromopyridine 13 (3.65 g, 14.5 mmol) in conc. HCl (35 mL) at −20 °C was added NaNO₂ (2 g, 29 mmol) slowly by small portions and the mixture was stirred at room temperature for 4 h. NaOH 10 M was added until pH 11 and the product was extracted with ethyl acetate (3 × 150 mL). The organic phase was washed with brine (100 mL) and dried over MgSO₄ and concentrated. The crude was purified by chromatography on silica gel (cyclohexane/ethyl acetate 4/1) to give 11 as a white powder (2.73 g, 70%). Mp 67–69 °C; ¹HNMR (CDCl₃, 200 MHz) δ 7.82 (d, J = 8.0 Hz, 1H), 7.18 ppm (d, J = 8.0 Hz, 1H); ¹³CNMR (CDCl₃, 50 MHz) δ 148.8, 143.5, 142.4, 124.3, 122.4 ppm. MS (70 eV): m/z (%) 271 (M⁺, 85), 192 (72), 110 (50), 75 (100), 50 (76); HRMS m/z calcd for C₅H₃Br₂ClN: 269.8315 (M + H), found: 269.8305.

General procedure for the preparation of 3-bromo-6-chloro-2-arylpyridine (10)

To a degassed toluene solution (4 mL) containing Pd(PPh₃)₄ (58 mg, 0.05 mmol) and 11 (269 mg, 1 mmol) were successively added degassed solutions of the corresponding boronic acid (1 mmol) in methanol (2 mL) and Na₂CO₃ (212 mg, 2 mmol) in water (2 mL). After heating for 6 h at 100 °C, the reaction mixture was cooled to room temperature, extracted with ethyl acetate and dried over MgSO₄. After concentration, the residue was purified by chromatography on silica gel (cyclohexane/ethyl acetate) to give the desired compounds.

3-Bromo-6-chloro-2-phenylpyridine (10a)

Yield: 92% (247 mg); mp 104–106 °C; ¹HNMR (CDCl₃, 250 MHz) δ 7.91 (d, J = 8.4 Hz, 1H), 7.75–7.65 (m, 2H), 7.50–7.40 (m, 3H), 7.16 ppm (d, J = 8.4 Hz, 1H); ¹³CNMR (CDCl₃, 62.5 MHz) δ 158.3, 149.6, 143.7, 138.1, 129.3, 129.2, 128.0, 123.8, 117.8 ppm. MS (70 eV): m/z (%) 269 (M⁺, 35), 188 (100), 153 (50), 76 (40), 50 (35); HRMS m/z calcd for C₁₁H₈BrClN (M + H): 267.9523, found: 267.9531.

3-Bromo-6-chloro-2-(4-methoxyphenyl)pyridine (10b)

Yield: 97% (289 mg); mp 93–95 °C; ¹HNMR (CDCl₃, 200 MHz) δ 7.90 (d, J = 8.0 Hz, 1H), 7.70 (d, J = 9.0 Hz, 2H), 7.13 (d, J = 8.0 Hz, 1H), 6.99 (d, J = 8.0 Hz, 1H), 3.87 ppm (s, 3H, OCH₃); ¹³CNMR (CDCl₃, 50 MHz) δ 160.3, 157.7, 149.5, 143.7, 130.9, 130.5, 123.2, 117.5, 113.3, 55.2 ppm. MS (70 eV): m/z (%) 299 (M⁺, 100), 218 (95), 175 (40), 140 (75), 113 (45), 63 (55); HRMS m/z calcd for C₁₂H₁₀BrClNO (M + H): 297.9629, found: 297.9640.

3-Bromo-6-chloro-2-(4-(methylthio)phenyl)pyridine (10c)

Yield: 64% (201 mg); mp 116–118 °C; ¹HNMR (CDCl₃, 200 MHz) δ 7.89 (d, J = 8.0 Hz, 1H), 7.66 (d, J = 8.5 Hz, 2H), 7.31 (d, J = 8.5 Hz, 1H), 7.13 (d, J = 8.0 Hz, 1H), 2.52 ppm (s, 3H, SCH₃); ¹³CNMR (CDCl₃, 50 MHz) δ 157.5, 149.6, 143.7, 140.4, 134.4, 129.7, 125.3, 123.6, 117.6, 15.2 ppm. MS (70 eV): m/z (%) 315 (M⁺, 100), 219 (18), 140 (20); HRMS m/z calcd for C₁₂H₁₀BrClNS (M + H): 313.9400, found: 313.9386.

4-(3-Bromo-6-chloropyridin-2-yl)benzaldehyde (10d)

Yield: 97% (287 mg); mp 143–145 °C; ¹HNMR (CDCl₃, 200 MHz) δ 10.10 (s, 1H, CHO), 8.01–7.96 (m, 3H), 7.86 (d, J = 8.0 Hz, 2H), 7.24 ppm (d, J = 8.5 Hz, 1H); ¹³CNMR (CDCl₃, 50 MHz) δ 191.8, 157.0, 150.0, 143.9, 143.7, 136.5, 130.2, 129.4, 124.7, 117.9 ppm. MS (70 eV): m/z (%) 297 (M⁺, 100), 266 (20), 216 (100), 187 (25), 152 (52), 125 (32), 75 (47), 50 (60); HRMS m/z calcd for C₁₂H₈BrClNO (M + H): 295.9472, found: 295.9476.

3-Bromo-6-chloro-2-[4-(dimethylamino)phenyl]pyridine (10e)

Yield: 61% (190 mg); ¹HNMR (CDCl₃, 200 MHz) δ 3.03 (s, 6H, N(CH₃)₂), 6.77 (d, J = 8.8 Hz, 2H), 7.04 (d, J = 8.3 Hz, 1H), 7.73 (d, J = 8.8 Hz, 2H), 7.85 ppm (d, J = 8.3 Hz, 1H); ¹³CNMR (CDCl₃, 50 MHz) δ 40.1, 111.0, 117.0, 122.2, 125.5, 130.56, 143.7, 149.3, 150.8, 158.0 ppm. MS (70 eV): m/z (%) 312 (M⁺, 100), 195 (26), 152 (22), 42 (30); HRMS m/z calcd for C₁₃H₁₃BrClNO (M + H): 310.9945, found: 310.9948.

4-(3-Bromo-6-chloropyridin-2-yl)pyridine (10f)

Pyridine 11 (272 mg, 1 mmol), 4-pyridine boronic acid (85% purity, 174 mg, 1.41 mmol) and Pd(PPh₃)₄ (58 mg, 0.05 mmol) were placed in a Schlenk tube under argon. Degassed dioxane (7 mL) and a degassed solution of aqueous Na₂CO₃ (1 M, 3 mL, 3 mmol) were added and the mixture was heated under reflux for 18 h. After heating cooling to room temperature, the mixture was extracted with ethyl acetate and dried over MgSO₄. After concentration, the residue was purified by chromatography on silica gel (cyclohexane/ethyl acetate 4/1) to give pyridine 10f as a white powder (150 mg, 56%). Mp 115–117 °C; ¹HNMR (CDCl₃, 200 MHz) δ 8.75 (s, 2H), 7.95 (d, J = 8.5 Hz, 1H), 7.61 (d, J = 4.0 Hz, 2H), 7.25 ppm (d, J = 8.5 Hz, 1H); ¹³CNMR (CDCl₃, 50 MHz) δ 155.5, 150.1, 149.7, 145.4, 144.0, 125.1, 123.7, 117.7 ppm. MS (70 eV): m/z (%) 270 (M⁺, 44), 189 (100), 162 (30), 127 (24); HRMS m/z calcd for C₁₀H₇BrClN₂ (M + H): 268.9476, found: 268.9484.

3-Bromo-6-chloro-2-(phenylethynyl)pyridine (14)

An oven-dried resealable tube was charged with 11 (269 mg, 1 mmol), CuI (5 mg, 0.03 mmol) and PdCl₂(PPh₃)₂ (7 mg, 0.01 mmol) then placed under argon. Degassed acetonitrile (1.5 mL) and triethylamine (0.2 mL, 1.5 mmol) were added. Finally, phenylacetylene (112.3 mg, 1.1 mmol) was added and the mixture was heated at 60 °C for 12 h. After cooling, the mixture was extracted with ethyl acetate (3 × 15 mL), dried and concentrated. The residue was purified by chromatography on silica gel (cyclohexane/ethyl acetate 3/1) to give 14 as a white product (200 mg, 68%). Mp 148–150 °C; ¹HNMR (CDCl₃, 200 MHz) δ 7.15 (d, J = 8.4 Hz, 1H), 7.37–7.41 (m, 3H), 7.62–7.67 (m, 2H), 7.85 ppm (d, J = 8.4 Hz, 1H). ¹³CNMR (CDCl₃, 50 MHz) δ 149.6, 143.4, 142.1, 132.2, 129.6, 128.4, 124.4, 122.1, 121.4, 95.4, 86.5 ppm. MS (70 eV): m/z (%) 252 ([M − C₃H₃]⁺, 99), 171 (45), 92 (83), 64 (100), 41 (86); HRMS m/z calcd for C₁₃H₈BrClN (M + H): 291.9523, found: 291.9503.

Cascade reaction of 10a under standard conditions. Formation of 16 and 15a

To a degassed toluene solution (7.5 mL) containing Pd(PPh₃)₄ (58 mg, 0.05 mmol) and pyridine 10a (134 mg, 0.5 mmol), degassed solutions of 2-formylbenzeneboronic acid 6a (186 mg, 1.25 mmol) in methanol (1.25 mL) and Na₂CO₃ (265 mg, 2.5 mmol) in water (2.5 mL) were successively added. After heating for 12 h at 100 °C, the reaction mixture was cooled to room temperature, extracted with ethyl acetate (3 × 20 mL) and dried over anhydrous MgSO₄. After filtration on Celite and concentration, the residue was purified by chromatography on silica gel (cyclohexane/ethyl acetate 9/1) to give 16 (90 mg, 61%) and 15a (30 mg, 15%).

2-[2-(6-Phenyl-pyridin-2-yl)-benzaldehyde]-benzaldehyde (16)

¹HNMR (CDCl₃, 200 MHz) δ 10.35 (s, 1H, CHO), 9.84 (s, 1H, CHO), 8.05 (d, J = 7.4 Hz, 1H), 8.00–7.00 ppm (m, 14H). MS (70 eV): m/z (%) 363 (M⁺, 80), 286 (100), 258 (30), 202 (30), 77 (80), 51 (65).

7,8-Dihydro-8-hydroxy-7-phenyl-indeno[1′,2′:4,5]pyrido[2,1-a]isoindol-5-one (15a)

Mp 237–239 °C; ¹HNMR (CDCl₃, 250 MHz) δ 7.98 (d, J = 7.3 Hz, 1H), 7.74 (d, J = 7.8 Hz, 1H), 7.66 (dt, J = 7.4, 1.9 Hz, 2H), 7.57 (dt, J = 7.4, 1.9 Hz, 2H), 7.50–7.38 (m, 2H), 7.18–7.05 (m, 3H), 6.82 (dd, J = 8.0, 1.9 Hz, 2H), 6.62 (d, J = 6.3 Hz, 1H), 6.32 (d, J = 6.3 Hz, 1H), 5.98 (brs, 1H, OH), 4.86 (d, J = 1.9 Hz, 1H); ¹³CNMR (CDCl₃, 62.5 MHz) δ 170.7, 144.1, 142.0, 137.9, 137.4, 135.2, 135.1, 132.5, 129.9, 129.6, 128.9, 128.2, 127.7, 126.4, 124.9, 123.9, 121.0, 120.6, 113.6, 104.4, 81.4, 73.3 ppm. MS (70 eV): m/z (%) 363 (M⁺, 95), 286 (100), 258 (32), 202 (20), 77 (55), 51 (30); HRMS m/z calcd for C₂₅H₁₇NNaO₂ (M + Na): 386.1151, found: 386.1176.

General procedure for the preparation of pentacycles (15)

An oven-dried resealable tube was charged with Pd(OAc)₂ (11.2 mg, 0.05 mmol, 5.0 mol%), XPhos ligand (24 mg, 0.05 mmol, 5.0 mol%), 2-formylbenzeneboronic acid (750 mg, 5 mmol), K₃PO₄ (1.37 g, 7.0 mmol) and pyridine 10 or 14 (1.0 mmol). The flask was evacuated and backfilled with argon then degassed dioxane (6 mL) was added through the rubber septum. After heating for 12 h at 100 °C, the reaction mixture was cooled to room temperature, extracted with ethyl acetate (3 × 20 mL) and dried over MgSO₄. After filtration on Celite and concentration, the residue was purified by chromatography on silica gel (cyclohexane/ethyl acetate) to give the pentacycles.

7,8-Dihydro-8-hydroxy-7-(4-methoxy-phenyl)-indeno[1′,2′:4,5]pyrido[2,1-a]isoindol-5-one (15b)

Yield: 52% (102 mg); mp 159–161 °C; ¹HNMR (CDCl₃, 400 MHz) δ 7.94 (d, J = 7.2 Hz, 1H), 7.80–7.45 (m, 5H), 7.50–7.40 (m, 2H), 6.77 (d, J = 9.0 Hz, 2H), 6.63 (d, J = 9.0 Hz, 2H), 6.61 (d, J = 6.2 Hz, 1H), 6.32 (d, J = 6.2 Hz, 1H), 5.94 (s, 1H), 4.91 (br s, 1H, OH), 3.65 ppm (s, 3H, OCH₃); ¹³CNMR (CDCl₃, 100 MHz) δ 170.6, 158.9, 144.0, 142.1, 137.2, 135.1, 134.9, 132.4, 129.95, 129.9, 129.5, 128.9, 127.65, 127.6, 124.8, 123.8, 121.0, 120.5, 113.6, 113.3, 104.4, 81.2, 72.7, 55.0 ppm. HRMS m/z calcd for C₂₆H₁₉NNaO₃ (M + Na): 416.1257, found: 416.1265.

7,8-Dihydro-8-hydroxy-7-(4-methylthio-phenyl)-indeno[1′,2′:4,5]pyrido[2,1-a]isoindol-5-one (15c)

Yield: 50% (100 mg); mp 97–99 °C; ¹HNMR (CDCl₃, 400 MHz) δ 7.94 (d, J = 7.8 Hz, 1H), 7.73 (d, J = 7.8 Hz, 1H), 7.68–7.62 (m, 2H), 7.60–7.54 (m, 2H), 7.48–7.38 (m, 2H), 6.90 (d, J = 9.0 Hz, 2H), 6.76 (d, J = 9.0 Hz, 2H), 6.62 (d, J = 6.0 Hz, 1H), 6.33 (d, J = 6.0 Hz, 1H), 5.69 (m, 1H), 4.90 (d, J = 2.5 Hz, 1H, OH), 2.33 ppm (s, 3H, SCH₃); ¹³CNMR (CDCl₃, 100 MHz) δ 170.6, 143.9, 141.8, 138.0, 137.2, 135.1, 134.9, 134.7, 132.5, 129.9, 129.6, 128.9, 127.6, 126.9, 126.1, 124.8, 123.9, 121.0, 120.5, 113.5, 104.3, 81.3, 72.9, 15.4 ppm. HRMS m/z calcd for C₂₆H₁₉NNaO₂S (M + Na): 409.1029, found: 432.1047.

7,8-Dihydro-8-hydroxy-7-(4-formyl-phenyl)-7H-indeno[1′,2′:4,5]pyrido[2,1-a]isoindol-5-one (15d)

Yield: 71% (139 mg); mp 151–153 °C; ¹HNMR (CDCl₃, 400 MHz) δ 9.85 (s, 1H, CHO), 7.95 (d, J = 7.2 Hz, 1H), 7.75 (d, J = 7.6 Hz, 1H), 7.70–7.63 (m, 2H), 7.62–7.54 (m, 2H), 7.60 (d, J = 8.6 Hz, 2H), 7.46 (dt, J = 7.2, 1.2 Hz, 1H), 7.42 (t, J = 7.6 Hz, 1H), 7.00 (d, J = 8.6 Hz, 2H), 6.63 (d, J = 6.0 Hz, 1H), 6.32 (d, J = 6.0 Hz, 1H), 5.99 (d, J = 2.4 Hz, 1H), 4.84 ppm (d, J = 2.5 Hz, 1H, OH); ¹³CNMR (CDCl₃, 50 MHz) δ 191.6, 170.5, 144.8, 143.6, 141.0, 137.0, 135.5, 134.9, 132.7, 130.1, 129.7, 129.4, 129.2, 127.3, 127.1, 124.8, 123.9, 121.1, 120.6, 114.1, 104.3, 81.4, 73.1 ppm. HRMS m/z calcd for C₂₆H₁₇NNaO₃ (M + Na): 414.1101, found: 414.1107.

7,8-Dihydro-8-hydroxy-7-(4-pyridyl)-7H-indeno[1′,2′:4,5]pyrido[2,1-a]isoindol-5-one (15f)

Yield (22%, 40 mg); mp 135–137 °C; ¹HNMR (CDCl₃, 200 MHz) δ 8.32 (d, J = 6.2 Hz, 2H), 7.96 (d, J = 7.2 Hz, 1H), 7.78–7.51 (m, 5H), 7.50–7.40 (m, 2H), 6.70 (d, J = 6.2 Hz, 2H), 6.63 (d, J = 6.4 Hz, 1H), 6.33 (d, J = 6.4 Hz, 1H), 5.98 (s, 1H), 4.85 ppm (br s, 1H, OH); ¹³CNMR (CDCl₃, 50 MHz) δ 170.4, 149.1, 147.5, 143.4, 140.5, 136.8, 134.9, 134.85, 132.9, 130.3, 129.9, 129.3, 127.3, 124.9, 124.0, 121.5, 121.1, 120.7, 114.2, 104.1, 81.2, 72.7 ppm. HRMS m/z calcd for C₂₄H₁₇N₂O₂ (M + H): 365.1285, found: 365.1269.

Acknowledgements

This research is supported by CNRS, Université de Lorraine, Ministère de l'Enseignement Supérieur et de la Recherche (Grant to Z.C.), the European Commission ERC Starting Grant (PhotoSi, 278912) and MAE (DirezioneGenerale per la Promozione del Sistema Paese). The authors thank the Service Commun de Diffraction X (Université de Lorraine) for providing access to crystallographic experimental facilities.

Notes and references

1. (a) M. Shimizu and T. Hiyama, Chem.–Asian J., 2010, 5, 1516; (b) Y. Hong, J. W. Y. Lam and B. Z. Tang, Chem. Commun., 2009, 4332 and references therein (c) Y. Hong, J. W. Y. Lam and B. Z. Tang, Chem. Soc. Rev., 2011, 40, 5361.
2. For some recent examples of highly luminescent solids, see: (a) O. Bolton, K. Lee, H. J. Kim, K. Y. Lin and J. Kim, Nat. Chem., 2011, 3, 205; (b) G. Bergamini, A. Fermi, C. Botta, U. Giovanella, S. Di Motta, F. Negri, R. Peresutti, M. Gingras and P. Ceroni, J. Mater. Chem. C, 2013, 1, 2717; (c) L. Chen, Y. Jiang, H. Nie, P. Lu, H. H. Y. Sung, I. D. Williams, H. Sing Kwok, F. Huang, A. Qin, Z. Zhao and B. Z. Tang, Adv. Funct. Mater., 2014, 24, 3621.
3. (a) Highly Efficient OLEDs with Phosphorescent Materials, ed. H. Yersin, Wiley-VCH, Berlin, 2007; (b) G. M. Farinola and R. Ragni, Chem. Soc. Rev., 2011, 40, 3467.
4. (a) I. D. W. Samuel and G. A. Turnbull, Chem. Rev., 2007, 107, 1272; (b) S. Forget and S. Chénais, Organic Solid-State Lasers, Springer Series in Optical Science, 2013, vol. 175; (c) G. M. Akselrod, E. R. Young, K. W. Stone, A. Palatnik, V. Bulovic and Y. R. Tischler, Phys. Rev. B: Condens. Matter Mater. Phys., 2014, 90, 035209.
5. See e.g.: (a) S. W. Thomas III, G. D. Joly and T. M. Swager, Chem. Rev., 2007, 107, 1339; (b) M. Schferling, Angew. Chem., Int. Ed., 2012, 51, 3532.
6. H. Langhals, T. Potrawa, H. Nöth and G. Linti, Angew. Chem., Int. Ed. Engl., 1989, 28, 478.
7. Z. Chamas, O. Dietz, E. Aubert, Y. Fort and V. Mamane, Org. Biomol. Chem., 2010, 8, 4815.
8. Z. Chamas, E. Marchi, A. Modelli, Y. Fort, P. Ceroni and V. Mamane, Eur. J. Org. Chem., 2013, 2316.
9. P. Eastwood, J. Gonzalez, S. Paredes, A. Nueda, T. Domenech, J. Alberti and B. Vidal, Bioorg. Med. Chem. Lett., 2010, 20, 1697.
10. V. Mamane and Y. Fort, Tetrahedron Lett., 2006, 47, 2337.
11. V. Mamane, F. Louërat, J. Iehl, M. Abboud and Y. Fort, Tetrahedron, 2008, 64, 10699.
12. The stability of 16 was however reduced in solution which prevented obtaining clean ¹³C NMR analysis.
13. For a review, see: R. Martin and S. L. Buchwald, Acc. Chem. Res., 2008, 41, 1461.
14. For an example from our laboratory, see: M. Abboud, E. Aubert and V. Mamane, Beilstein J. Org. Chem., 2012, 8, 253.
15. J. N. Demas and G. A. Crosby, J. Phys. Chem., 1971, 75, 991.
16. M. Montalti, A. Credi, L. Prodi and M. T. Gandolfi, in Handbook of Photochemistry, Taylor & Francis, London, 3rd edn, 2006, ch. 10.
17. J. C. De Mello, H. F. Wittmann and R. H. Friend, Adv. Mater., 1997, 9, 230.
18. A. Altomare, G. Cascarano, C. Giacovazzo, A. Guagliardi, M. C. Burla, G. Polidori and M. Camalli, J. Appl. Crystallogr., 1994, 27, 435.
19. G. M. Sheldrick, SHELXL-97, University of Göttingen, Germany, 1997.

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Footnotes

† Electronic supplementary information (ESI) available: Copy of ¹H and ¹³C NMR spectra of all compounds, ORTEP view of compounds 2, 15a and 15d. CCDC 1027764–1027766. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4ra12155d

‡ New address: Institut de Chimie de Strasbourg, UMR 7177, Equipe LASYROC, 1 rue Blaise Pascal, 67008 Strasbourg, France, E-mail: E-mail: vmamane@unistra.fr.

§ 2: C₂₁H₁₇NO₂, M_r = 315.36, crystal dimensions: 0.19 × 0.15 × 0.09 mm, triclinic, space group P1̄, a = 8.3902(4) Å, b = 9.4235(5) Å, c = 10.5655(5) Å, α = 68.634(5)°, β = 86.055(4)°, γ = 83.059(4)°, V = 771.97(7) ų, T = 110(2) K, Z = 2, ρ_calcd = 1.357 g cm⁻³, μ = 0.688 mm⁻¹, 8377 reflections collected, 3099 unique reflections, R_int = 0.0408, 2θ_max = 152.34°, 223 parameters, R₁ = 0.0636, wR₂ = 0.1703, ρ_min = −0.241 e Å⁻³, ρ_max = 0.359 e Å⁻³. 15a: C₂₅H₁₇NO₂, M_r = 363.40, crystal dimensions: 0.23 × 0.18 × 0.09 mm, monoclinic, space group P2₁/c, a = 10.6552(3) Å, b = 8.1691(2) Å, c = 20.6721(6) Å, β = 104.472(3)°, V = 1742.28(8) ų, T = 110(2) K, Z = 4, ρ_calcd = 1.385 g cm⁻³, μ = 0.702 mm⁻¹, 9695 reflections collected, 3235, unique reflections, R_int = 0.0146, 2θ_max = 140.26°, 254 parameters, R₁ = 0.0379, wR₂ = 0.0910, ρ_min = −0.263 e Å⁻³, ρ_max = 0.283 e Å⁻³. 15d: 2(C₂₆H₁₇NO₃), CH₂Cl₂, M_r = 867.74, crystal dimensions: 0.20 × 0.14 × 0.09 mm, orthorhombic, space group Pna2₁, a = 26.5772(4) Å, b = 11.8718(2) Å, c = 12.8742(2) Å, V = 4062.06(11) ų, T = 100(2) K, Z = 4, ρ_calcd = 1.419 g cm⁻³, μ = 1.914 mm⁻¹, 40 982 reflections collected, 7997, unique reflections, R_int = 0.0151, 2θ_max = 145.80°, 571 parameters, R₁ = 0.0356, wR₂ = 0.0961, refined inversion twin population parameter (Flack parameter): 0.244(10). ρ_min = −0.277 e Å⁻³, ρ_max = 0.498 e Å⁻³.

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