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DOI: 10.1055/s-0034-1380696
One-Pot Synthesis of Novel Cyclopentene-Fused Octahydropyridoquinolines and Octahydrophenanthrolines
Publication History
Received: 02 February 2015
Accepted after revision: 09 April 2015
Publication Date:
26 May 2015 (online)
Abstract
New cyclopentene-fused octahydropyridoquinolines and octahydrophenanthrolines were prepared by a stereoselective three-component cyclocondensation of benzene-1,4-diamine, cyclopenta-1,3-diene, and an aromatic aldehyde. Single-crystal X-ray diffraction data provided evidence for the formation of cyclopentene-fused octahydropyridoquinolines and octahydrophenanthrolines with a syn-planar arrangement of the cyclopentene rings. The cyclocondensation of benzene-1,4-diamine, cyclopenta-1,3-diene, and formaldehyde gave new type of polycyclic compound containing four cyclopentene moieties oriented in a mutually antiplanar manner.
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Key words
Diels–Alder reactions - electrophilic aromatic substitutions - heterocycles - polycycles - fused-ring systemsThe multicomponent coupling strategy is recognized as an effective and powerful approach that permits ready access to polycarbocycles and to polyheterocycles.[1] Among nitrogen heterocycles, quinolines and their derivatives are a class of organic compounds that are attracting interest from both synthetic and medicinal chemists.[2] A three-component modification of the Povarov reaction, which can also be classified as a formal [4+2] cycloaddition of an aromatic imine (Schiff base) with a nucleophilic olefin (the aza-Diels–Alder reaction) is an important tool for the synthesis of quinoline derivatives.[1b] [3] By using this method, cyclopentene-fused tetrahydroquinolines have been synthesized from arylamines, aromatic aldehydes, and cyclopenta-1,3-diene.[4] The involvement of aromatic diamines in a similar reaction provides a rapid route for the synthesis of diazaheterocycles fused to two cyclopentene moieties. Whereas the reaction of aromatic amines, aldehydes, and alkenes has been widely used, there are only a few reports on the use of isomeric benzenediamines in similar reactions.[5] We investigated the cyclocondensation of benzene-1,4-diamine with cyclopenta-1,3-diene and various aromatic aldehydes or formaldehyde, and we synthesized several novel octahydropyridoquinolines and octahydrophenanthrolines fused to cyclopentene moieties.
Benzene-1,4-diamine (1) has two free ortho positions at each amine group, and a three-component condensation involving this substrate would be expected to give two regioisomeric bis adducts with distant and close cyclopentene moieties. The trifluoroacetic acid-catalyzed reaction of benzene-1,4-diamine 1, an aromatic aldehyde 2, and cyclopenta-1,3-diene in a 1:2:6 molar ratio in acetonitrile at room temperature for 20 minutes gave a 1:1 mixture of products 3 and 4, which were easily separated by column chromatography (Scheme [1]).


Note that a Povarov monoadduct (involving one of the two amine groups) was not formed, even when an equimolar amount of the aldehyde was used. It is likely that adduct formation at the second amine group occurs at a higher rate.
The structures of newly prepared compounds 3a–d and 4a–d were established by using one- and two-dimensional 1H and 13C NMR spectroscopy, mass spectrometry, and IR spectroscopy and they were confirmed by single-crystal X-ray diffraction studies on compounds 3a, 4a, and 4b.
MALDI/TOF mass spectrometry showed that compound 3a [Rf = 0.58 (hexane–EtOAc, 3:1)] and compound 4a [Rf = 0.47 (hexane–EtOAc, 3:1)] have identical molecular masses. The sets of pairwise-matching signals of all atoms in the 1H and 13C NMR spectra of the less-polar compound 3a suggested that this compound has a C 2-symmetric structure. The coupling constants of 8 Hz for the vicinal protons at the stereogenic carbon centers indicate that they have a cis-arrangement with respect to one another, in agreement with the endo,cis-direction of the Povarov reaction. A single-crystal X-ray structure determination of 3a confirmed the NMR-based assignment of a cis,cis relative stereochemistry. The octahydropyridoquinoline core is relatively flat, and the cyclopentene moieties are coplanar and syn-oriented relative to the molecular plane (Figure [1]).


The symmetrically arranged stereogenic carbon atoms in positions 3a and 9a, 4 and 10, and 6b and 12b have the corresponding pairwise-identical S*, R*, and S* relative configurations, respectively, and the structure (3aS*,4R*,6bS*,9aS*,10R*,12bS*)-4,10-bis(2-fluorophenyl)-3,3а,4,5,6b,9,9a,10,11,12b-decahydrocyclopenta[c]cyclopenta[4,5]pyrido[2,3-g]quinoline can be assigned to compound 3a.
The more-polar compound 4a has a CS -symmetric structure, and its 1H and 13C spectra also contain a set of pairwise-identical chemical shifts, although the symmetrically arranged stereogenic carbon atoms 1 and 6, 6a and 12a, and 9a and 9 have pairwise-opposite relative configurations 1S* and 6R*, 6aS* and 12aR*, and 9aR* and 9dS*, respectively. The coupling constant (9 Hz) of the vicinal protons at the stereogenic carbon centers confirms their cis-orientation. A single-crystal X-ray structure determination of 4a (Figure [2]) confirmed the NMR assignments and established that 4a has the structure (3aS*,4R*,6bS*,9aS*,10R*,12bS*)-4,10-bis(2-fluorophenyl)-3,3a,4,5,6b,9,9a,10,11,12b-decahydrocyclopenta[c]cyclopenta[4,5]pyrido[2,3-g]quinoline. Remarkably, the signal of the ortho-aromatic protons H-3 and H-4 in 4a is manifested as a broad singlet (w1/2 = 30 Hz), whereas the signal for the para-aromatic protons H-6 and H-12 in 3a is a narrow singlet.


The similarities of the 1H and 13C NMR spectra of compounds 3b–d to those of 3a, in conjunction with the single-crystal X-ray diffraction data for 3a (Figure [1]), indicate that the compounds belong to the pyridoquinoline series. The similarities among the spectra of compounds 4a–d, in conjunction with the X-ray data for compounds 4a (Figure [2]) and 4b (Figure [3]), unambiguously confirms that these compounds belong to the 4,7-phenanthroline series.


The piperidine rings in crystals of 3a, 4a, and 4b have a boat-type conformation with an equatorial aryl group at the flagpole C4 and C10 atoms in 3a (Figure [1]) or at the C1 and C6 carbon atoms in 4a and 4b (Figures [2] and 3).
A stepwise mechanism[6] for the formation of isomeric pentacyclic core of compounds 3 and 4 is shown in Scheme [2]. Diamine 1 reacts with the aldehyde to form the bisimine ion A in the presence of trifluoroacetic acid as a catalyst. Nucleophilic attack by cyclopenta-1,3-diene at the carbon atom of one of the iminium moieties A gives the carbenium ion B, which undergoes a Friedel–Crafts-type alkylation to form intermediate C. This tautomerizes to give the imine ion D. The second iminium moiety in intermediate D can undergoes similar bond-forming and bond-breaking steps to form carbenium ion E. The subsequent intramolecular electrophilic substitution at one of the two ortho-positions of the benzene ring can occur in two ways: route a or route b. Subsequent deprotonation and rearomatization of the resulting intermediate F or F′ leads to the corresponding pyridoquinoline derivative 3 or the phenanthroline derivative 4, respectively.


The use of formaldehyde as a coupling partner in three-component reactions gives interesting results.[5a] [7] The three-component reaction of formaldehyde, cyclopenta-1,3-diene, and aniline or its para-substituted derivatives gave high yields of the corresponding benzodicyclopentaquinolizines with an antiplanar arrangement of the cyclopentene rings.[8] We found that the reaction of benzene-1,4-diamine (1) with formaldehyde and cyclopenta-1,3-diene in acetonitrile gave the nonacyclic compound 5 containing four mutually antiplanar cyclopentene moieties (Scheme [3]).


The structure of compound 5 was determined by means of single-crystal X-ray diffraction (Figure [4]). As can be seen, the symmetric structure of compound 5 contains a planar central pentacyclic moiety annulated to four antiplanar cyclopentene rings.
The signals in the NMR spectra of compound 5 were assigned by using one- and two-dimensional methods. The 13C NMR spectrum of nonacycle 5 should contain eight signals as a result of its centrosymmetric structure, but we observed seven signals. The eighth signal of aromatic atoms C18b and C18c was detected in the HMBC spectrum [long-range correlations of H 7, 9, 16, 18 (δ = 3.12 ppm) and C18b, 18c (δ = 137.04 ppm)]. The MALDI/TOF mass spectrum of compound 5 contains the corresponding molecular ion. On the basis of these results we assigned the structure (3аR*,3dR*,6aS*,9aS*,12aR*,12dR*,15aS*,18aS*)-1,3a,3d,6, 6a,7,9,9a,10,12a,12d,15,15a,16,18,18a-hexadecahydrodicyclopenta[a,k]biscyclopenta[4,5]pyrido[1,2,3-de:3′,2′,1′-gh]-4,7-phenanthroline to compound 5.


In conclusion, we have developed the three-component acid-catalyzed one-pot cyclocondensation of benzene-1,4-diamine with an aromatic aldehyde and cyclopenta-1,3-diene that results in stereoselective formation of novel cyclopentene-fused octahydropyridoquinolines and octahydrophenanthrolines. The reaction of benzene-1,4-diamine with formaldehyde and cyclopenta-1,3-diene gives a 4,7-phenanthroline-type polycyclic compound with four mutually antiplanar cyclopentene moieties.
The starting materials were purchased from Acros Organics. One-dimensional (1H and 13C) and two-dimensional (COSY, NOESY, HSQC, and HMBC) NMR spectra of all compounds were recorded on a Bruker Avance-400 spectrometer at 400.13 MHz for 1H and 100.62 MHz for 13C or on a Bruker Avance III 500 spectrometer at 500.17 MHz for 1H and 125.78 MHz for 13C; the spectrometers were equipped with broadband observer probe. All the measurements were performed by the standard Bruker methods. Chemical shifts are given in ppm relative to TMS as the internal standard. IR spectra were recorded on Bruker VE Vertex-70v spectrometer using KBr pellets. Mass spectra were recorded on a Bruker Autoflex III instrument operated in the MALDI-TOF regime with positive ionization using 2,5-dihydroxybenzoic acid or α-cyano-4-hydroxycinnamic acid as the matrix. Melting points were determined on a Boetius hot-stage microscope. Elemental analysis was performed on Carlo Erba EA-1108 CHN-OS analyzer. Column chromatography was performed on silica gel (<0.06 mm). TLC was performed on precoated silica gel plates (Silufol); spots were visualized with I2 vapor.
Single crystals of 3a, 4a, 4b, and 5 were grown from solutions in 1:1 hexane–EtOAc soln at r.t. X-ray diffraction data were collected on a XCalibur Eos diffractometer by using graphite-monochromated Mo-Kα radiation (λ = 0.71073 Å). Data were collected and processed by using the CrysAlisPro program (Oxford Diffraction Ltd., Versions 1.171.36.28 and 1.171.36.20). Structure solution and refinement were performed with SHELXL97.[9] The structure was refined by a full-matrix least-square technique, using anisotropic thermal parameters for nonhydrogen atoms and a riding model for hydrogen atoms. These X-ray crystallographic data have been deposited at the Cambridge Crystallographic Data Center.[10]
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Decahydrocyclopenta[c]cyclopenta[4,5]pyrido[2,3-g]quinolines 3a–d and Decahydrocyclopenta[a,k]-4,7-phenanthrolines 4a–d; General Procedure
TFA (0.15 mL, 2 mmol), freshly distilled cyclopenta-1,3-diene (0.5 ml, 6 mmol), and aryl aldehyde 2a–d (2 mmol) were added sequentially to a solution of diamine 1 (0.11 g, 1 mmol) in MeCN (5 mL). The mixture was stirred for 0.3 h under argon until the starting amine disappeared [TLC, hexane–EtOAc (3:1)]. The solvent was evaporated, and the residue was diluted with sat. aq NaHCO3 (1 mL) and extracted with EtOAc (3 × 5 mL). The organic layer was concentrated and the residue was purified by column chromatography (silica gel, hexane).
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(3aS*,4R*,6bS*,9aS*,10R*,12bS*)-4,10-Bis(2-fluorophenyl)-3,3a,4,5,6b,9,9a,10,11,12b-decahydrocyclopenta[c]cyclopenta[4,5]pyrido[2,3-g]quinoline (3a)
Off-white solid; yield: 130 mg (28%); mp 132–134 °C (hexane).
IR (KBr): 3349 (NH), 3050 (–CH=CH–), 1616 and 1455 (Ar), 1111 (Ar–F) cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.81–1.87 and 2.61–2.67 (m, 4 H, CH2, H-3, CH2, H-9), 3.13 (dd, J = 9.2, 2.8 Hz, 2 H, H-3a, H-9a), 4.08 (d, J = 8.0 Hz, 2 H, H-6b, H-12b), 4.87 (br s, 2 H, H-4, H-10), 5.68 (br s, 2 H, H-2, H-8), 5.83 (br s, 2 H, H-1, H-7), 6.47 (s, 2 H, H-6, H-12), 7.06–7.68 (m, 8 H, Ar).
13C NMR (100 MHz, CDCl3): δ = 31.7 (C-3, C-9), 43.1 (C-3a, C-9a), 46.3 (C-6b, C-12b), 51.6 (C-4, C-10), 115.1 (2 J C–F = 22 Hz, C-3′, C-3′′), 116.1 (C-6, C-12), 125.0 (C-6a, C-12a), 127.3 (C-5′, C-6′, C-5′′, C-6′′), 128.3 (J C–F = 8 Hz, C-4′, C-4′′), 130.3 (C-2, C-8), 130.3 (2 J C–F = 6 Hz, C-1′, C-1′′), 134.2 (C-1, C-7), 138.6 (C-5ª, C-11ª), 160.1 (1 J C–F = 245 Hz, C-2′, C-2′′).
MS (MALDI-TOF): m/z = 452 [M+].
Anal. Calcd for C30H26F2N2: C, 79.62; H, 5.79; N, 6.19. Found: C, 79.50; H, 5.70; N, 6.24.
Crystal data: C30H26N2F2, 452.53, monoclinic, P21/a (no. 14), a = 9.6504(5) Å, b = 14.5345(8) Å, c = 17.5334(10) Å, β = 97.149(5)°, V = 2440.2(2) Å3 T = 293.(2) K, Dcalcd = 1.232 g/m3, Z = 4; Reflections collected = 13736, independent reflections = 7060 (R int = 0.0235), which were used in all calculations. The final R 1 was 0.0695 [I > 2σ(I)] and wR 2 was 0.1974 (all data).[10]
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(3aS*,4R*,6bS*,9aS*,10R*,12bS*)-4,10-Bis[4-(trifluoromethyl)phenyl]-3,3a,4,5,6b,9,9a,10,11,12b-decahydrocyclopenta[c]cyclopenta[4,5]pyrido[2,3-g]quinoline (3b)
Off-white solid; yield: 150 mg (26%); mp 178–180 °C (hexane).
IR (KBr): 3370 (NH), 3050 (–CH=CH–), 1619 and 1480 (Ar), 1324 (F3C–Ar) cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.78–1.82 and 2.59–2.66 (m, 4 H, CH2, H-3, CH2, H-9), 2.94–3.03 (m, 2 H, H-3a, H-9a), 4.06 (d, J = 8.1 Hz, 2 H, H-6b, H-12b), 4.63 (d, J = 3.0 Hz, 2 H, H-4, H-10), 5.67 (br s, 2 H, H-2, H-8), 5.84 (br s, 2 H, H-1, H-7), 6.48 (s, 2 H, H-6, H-12), 7.59–7.66 (m, 8 H, Ar).
13C NMR (100 MHz, CDCl3): δ = 31.3 (C-3, C-9), 45.6 (C-6b, C-12b), 46.3 (C-3a, C-9a), 58.3 (C-4,C-10), 116.0 (C-6, C-12), 121.1 (3 J C–F = 43 Hz, C-4′, C4′′), 124.9 (C-6a, C-12a), 125.6 and 126.8 (Ar), 129.5 (1 J C–F = 218 Hz, CF3), 129.9 (C-2, C-8), 133.9 (C-1, C-7), 135.8 (C-5a, C-11a), 138.7 (C-4′, C-4′′), 147.2 (C-1′, C-1′′).
MS (MALDI-TOF): m/z = 552 [M+].
Anal. Calcd for C32H26F6N2: C, 69.56; H, 4.74; N, 5.07. Found: C, 69.46; H, 4.79; N, 4.96.
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(3aS*,4R*,6bS*,9aS*,10R*,12bS*)-4,10-Bis-(3-Chlorophenyl)-3,3a,4,5,6b,9,9a,10,11,12b–decahydrocyclopenta[c]cyclopenta[4,5]pyrido[2,3-g]quinoline (3c)
Off-white solid; yield: 130 mg (26%); mp 98–100 °C (hexane).
1H NMR (400 MHz, CDCl3): δ = 1.80–1.85 and 2.59–2.70 (m, 4 H, CH2, H-3, CH2, H-9), 2.94–2.98 (m, 2 H, H-3a, H-9a), 4.04 (d, J = 8.0 Hz, 2 H, H-6b, H-12b), 4.54 (d, J = 2.9 Hz, 2 H, H-4, H-10), 5.68 (br s, 2 H, H-2, H-8), 5.83 (br s, 2 H, H-1, H-7), 6.44 (s, 2 H, H-6, H-12), 7.28–7.48 (m, 8 H, Ar).
13C NMR (100 MHz, CDCl3): δ = 31.3 (C-3, C-9), 45.6 (C-6b, C-12b), 46.3 (C-3a, C-9a), 58.2 and 58.8 (C-4,C-10), 116.0 (C-6, C-12), 123.1 (C-6a, C-12a), 130.3 (C-2, C-8), 133.9 (C-1, C-7), 135.6 (C-3′, C-3′′), 138.2 (C-5a, C-11a), 126.7–129.7 (Ar), 145.3 (C-1′, C-1′′).
MS (MALDI-TOF): m/z = 484 [M+].
Anal. Calcd for C30H26Cl2N2: C, 74.22; H, 5.44; N, 5.77. Found: C, 74.50; H, 5.68; N, 5.83.
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(3aS*,4R*,6bS*,9aS*,10R*,12bS*)-4,10-Diphenyl-3,3a,4,5,6b,9,9a,10,11,12b-decahydrocyclopenta[c]cyclopenta [4,5]pyrido[2,3-g]-quinoline (3d)
Off-white solid; yield: 120 mg (28%); mp 112–114 °C (hexane).
1H NMR (400 MHz, CDCl3): δ = 1.80–1.86 and 2.65–2.75 (m, 4 H, CH2, H-3, CH2, H-9), 2.95–3.18 (m, 2 H, H-3a, H-9a), 4.05 (d, J = 7.9 Hz, 2 H, H-6b, H-12b), 4.59 (d, J = 3.4 Hz, 2 H, H-4, H-10), 5.68 (br s, 2 H, H-2, H-8), 5.83 (br s, 2 H, H-1, H-7), 6.46 (s, 2 H, H-6, H-12), 7.21–7.58 (m, 10 H, Ar).
13C NMR (100 MHz, CDCl3): δ = 1.5 (C-3, C-9), 45.9 (C-3a, C-9a), 46.5 (C-6b, C-12b), 58.7 (C-4, C-10), 115.4 (C-6, C-12), 124.9 (C-6a, C-12a), 126.5–128.7 (Ar), 130.3 (C-2, C-8), 134.0 (C-1, C-7), 138.6 (C-5a, C-11a), 143.3 (C-1′, C-1′′).
MS (MALDI-TOF): m/z = 416 [M+].
Anal. Calcd for C30H28N2: C, 86.50; H, 6.78; N, 6.73. Found: C, 86.73; H, 6.82; N, 6.71.
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(1R*,6S*,6aR*,9aR*,9dS*,12aS*)-1,6-Bis(2-fluorophenyl)-1,2,5,6,6a,7,9a,9d,12,12a-decahydrodicyclopenta[a,k]-4,7-phenanthroline (4a)
Off-white solid; yield: 150 mg (30%); mp 138–140 °C (hexane).
IR (KBr): 3358 (NH), 3051 (–CH=CH–), 1611 and 1454 (Ar), 1092 (Ar-F) cm–1.
1H NMR (400.17 MHz, CDCl3): δ = 2.05 (dd, J = 14.2, 9.0 Hz, 2 H, CH2, H-7, H-12) and 2.60 (dd, J = 15.0, 3.2 Hz, 2 H, CH2, H-7, H-12), 3.37 (dd, J = 9.0, 5.0 Hz, 2 H, H-6a, H-12a), 3.50 (br s, 2 H, NH, w1/2 = 24 Hz), 4.52 (d, J = 8.4 Hz, 2 H, H-9a, H-9d), 4.64 (br s, 2 H, H-1, H-6), 5.71 (br s, 2 H, H-9, H-10), 5.82 (br s, 2 H, H-8, H-11), 6.53 (br s, 2 H, H-3, H-4, w 1/2 = 30 Hz), 7.05–7.65 (m, 8 H, Ar).
13C NMR (125.78 MHz, CDCl3): δ = 33.4 (C-7, C-12), 43.3 (C-9a, C-9d), 45.3 (C-12a, C-6a), 55.2 (C-1, C-6), 115.2 (C-3′, C-3′′), 124.2 (C-3, C-4), 125.2 (C-2a, C-4a), 126.7 (C-9b, C-9c), 126.8 (C-1′, C-1′′), 127.5, 128.4, 130.9 (Ar), 131.1 (C-11, C-8), 133.2 (C-10, C-1), 160.0 (d, 1 J C–F = 233.5 Hz, C-2, C-2′′).
MS (MALDI-TOF): m/z = 452 [M+].
Anal. Calcd for C30H26F2N2: C, 79.62; H, 5.79; N, 6.19. Found: C, 79.53; H, 5.70; N, 6.32.
Crystal data: C30H26N2F2, M = 453.30, monoclinic, P21/n (no. 14), a = 5.4892(8) Å, b = 14.202(2) Å, c = 28.607(2) Å, β = 89.238(10)°, V = 2230.0(5) Å3, T = 293.(2) K, Dcalcd = 1.356 g/cm3, Z = 4; reflections collected = 5121, independent reflections = 4119 (R int = 0.0356). The final R 1 was 0.1032 [I > 2σ(I)] and wR 2 was 0.2695 (all data).[10]
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(1R*,6S*,6aR*,9aR*,9dS*,12aS*)-1,6-Bis[4-(trifluoromethyl)phenyl]-1,2,5,6,6a,7,9a,9d,12,12a-decahydrodicyclopenta[a,k]-4,7-phenanthroline (4b)
Off-white solid; yield: 180 mg (32%); mp 115–117 °C (hexane).
IR (KBr): 3351 (NH), 3051 (–CH=CH–), 1619 (Ar), 1325 (F3C–Ar) cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.01–2.08 and 2.57–2.62 (m, 4 H, CH2, H-7, H-12), 3.22–3.29 (m, 2 H, H-12a, H-6a), 4.42 (d, J = 2.9 Hz, 2 H, H-1, H-6), 4.53 (d, J = 8.0 Hz, 2 H, H-9a, H-9d), 5.74 (br s, 2 H, H-9, H-10), 5.83 (br s, 2 H, H-8, H-11), 6.51 (s, 2 H, H-3, H-4), 7.56 and 7.68 (both d, J = 8.1 Hz, 8 H, Ar).
13C NMR (100 MHz, CDCl3): δ = 33.6 (C-12, C-7), 45.6 (C-9a, C-9d), 46.1 (C-12a, C-6a), 61.4 (C-1, C-6), 115.3 (C-3, C-4), 121.1 (2 J C–F = 43 Hz, C-4′, C-4′′), 125.4 and 126.5 (Ar), 127.3 (C-9d, C-9c), 129.5 (1 J C–F = 218 Hz, CF3), 131.1 (C-11, C-8), 133.2 (C-10, C-9), 141.5 (C-2a, C-4a), 147.3 (C-1′, C-1′′).
MS (MALDI-TOF): m/z = 552 [M+].
Anal. Calcd for C32H26F6N2: C, 69.56; H, 4.74; N, 5.07. Found: C, 69.33; H, 4.79; N, 5.05.
Crystal data: C32H26N2F6, M = 552.40, orthorhombic, Pna21 (no. 33), a = 11.1207(5) Å, b = 15.0240(7) Å, c = 15.8131(5) Å, V = 2642.01(19) Å3, T = 293.(2) K, Dcalcd = 1.338 g/cm3, Z = 4; reflections collected = 6738, independent reflections = 4293 (R int = 0.0128). The final R 1 was 0.0527 [I>2σ(I)] and wR 2 was 0.1576 (all data).[10]
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(1R*,6S*,6aR*,9aR*,9dS*,12aS*)-1,6-Bis(3-chlorophenyl)-1,2,5,6,6a,7,9a,9d,12,12a-decahydrodicyclopenta[a,k]-4,7-phenanthroline (4c)
Off-white solid; yield: 140 mg (29%); mp 98–100 °C (hexane).
1H NMR (400 MHz, CDCl3): δ = 2.01–2.10 and 2.56–2.60 (m, 4 H, CH2, H-7, H-12), 3.17–3.24 (m, 2 H, H-12a, H-6a), 4.32 (d, J = 3.6 Hz, 2 H, H-1, H-6), 4.48 (d, J = 8.0 Hz, 2 H, H-9a, H-9d), 5.72 (br s, 2 H, H-9, H-10), 5.81 (br s, 2 H, H-8, H-11), 6.48 (s, 2 H, H-3, H-4), 7.28–7.48 (m, 8 H, Ar).
13C NMR (100 MHz, CDCl3): δ = 33.1 (C-12, C-7), 45.5 (C-9a, C-9d), 46.0 (C-12a, C-6a), 61.2 (C-6, C-1), 115.5 (C-3, C-4), 127.2 (C-9b, C-9c), 128.0 and 129.8 (Ar), 130.9 (C-11, C-8), 133.2 (C-10, C-9), 134.5 (C-3′, C-3′′), 141.5 (C-2a, C-4a), 144.7 (C-1′, C1′′).
MS (MALDI-TOF): m/z = 484 [M+].
Anal. Calcd for C30H26Cl2N2: C, 74.22; H, 5.40; N, 5.77. Found: C, 74.01; H, 5.58; N, 5.89.
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(1R*,6S*,6aR*,9aR*,9dS*,12aS*)-1,6-Diphenyl-1,2,5,6,6a,7,9a,9d,12,12a-decahydrodicyclopenta[a,k]-4,7-phenanthroline (4d)
Off-white solid; yield: 130 mg (30%); mp 73–75 °C (hexane).
1H NMR (400 MHz, CDCl3): δ = 1.81–1.87 and 2.64–2.71 (m, 4 H, CH2, H-7, H-12), 2.98–3.02 (m, 2 H, H-12a, H-6a), 4.06 (d, J = 8.0 Hz, 2 H, H-9a, H-9d), 4.59 (d, J = 8.2 Hz, 2 H, H-1, H-6), 5.68 (br s, 2 H, H-9, H-10), 5.82 (br s, 2 H, H-8, H-11), 6.48 (m, 2 H, H-3, H-4), 7.28–7.50 (m, 10 H, Ar).
13C NMR (100 MHz, CDCl3): δ = 35.6 (C-7, C-12), 45.4 (C-9a, C-9d), 46.1 (C-12a, C-6a), 61.7 (C-1, C-6), 116.0 (C-3, C-4), 127.1 (C-9b, C-9c), 128.7 (Ar), 130.3 (C-8, C-11), 134.0 (C-9, C-10), 141.8 (C-2a, C-4a).
MS (MALDI-TOF): m/z = 416 [M+].
Anal. Calcd for C30H28N2: C, 86.50; H, 6.78; N, 6.73. Found: C, 86.58; H, 6.70; N, 6.78.
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(3аR*,3dR*,6aS*,9aS*,12aR*,12dR*,15aS*,18aS*)-1,3a,3d,6,6a,7,9,9a,10,12a,12d,15,15a,16,18,18a-Hexadecahydrodicyclopenta[a,k]biscyclopenta[4,5]pyrido[1,2,3-de:3′,2′,1′-gh]-4,7-phenanthroline (5)
A solution of diamine 1 (0.15 g, 1.4 mmol) and TFA (0.15 mL, 2 mmol) in MeCN (15 ml) was added to a mixture of freshly distilled cyclopenta-1,3-diene (10 mmol) and 37% aq HCHO (0.83 mL, 10 mmol) at 0 °C. The mixture was stirred under argon for 1.5 h until the reaction was complete [TLC, hexane–EtOAc (3:1)]. The solvent was evaporated, and the residue was diluted with sat. aq NaHCO3 (1 mL) and extracted with EtOAc (3 × 10 mL). The organic layer was concentrated and the residue was purified by column chromatography [silica gel, hexane–EtOAc (10:1)] to give an off-white solid; yield: 85 mg (20%); mp 200–202 °C (hexane).
1H NMR (500 MHz, CDCl3): δ = 2.37 and 2.78 (d, J = 11.0 Hz, 8 H, CH2, H-1, H-6, H-10, H-15), 3.01 (m, 4 H, H-6a, H-9a, H-15a, H-18a), 3.02 and 3.12 (m, 8 H, H-7, H-9, H-16, H-18), 4.19 (br s, 4 H, H-3a, H-3d, H-12a, H-12d), 5.61 (br s, 4 H, H-2, H-5, H-11, H-14), 5.82 (m, 4 H, H-3, H-4, H-12, H-13).
13C NMR (100 MHz, CDCl3): δ = 34.0 (C-6a, C-9a, C-15a, C-18a), 38.0 (C-1, C-6, C-10, C-15), 43.9 (C-3a, C-3d, C-12a, C-12d), 56.1 (C-7, C-9, C-16, C-18), 126.0 (C-3b, C-3c, C-12b, C-12c), 131.2 (C-3, C-4, C-12, C-13), 132.9 (C-2, C-5, C-11, C-14).
MS (MALDI-TOF): m/z = 420 [M+].
Anal. Calcd for C30H32N2: C, 85.67; H, 7.67; N, 6.66. Found: C, 85.72; H, 7.70; N, 6.70.
Crystal data of 5: C30H34N2, M = 422.59, monoclinic P21 (no. 4), a = 10.7913(5) Å, b = 9.7214(4) Å, c = 11.0560(6) Å, β = 105.090(5)°, V = 1119.85(9) Å3, T = 293.(2) K, Dcalcd = 1.253 g/cm3, Z = 2; reflections collected = 3203, independent reflections = 2357 (R int = 0.0191). The final R 1 was 0.0357 [I > 2σ(I)] and wR 2 was 0.0913 (all data).[10]
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Acknowledgment
This work has been financially supported by the Russian Fund for Basic Researches (Grant 14-03-00286) and by the Program Presidium of the Russian Academy of Sciences.
Supporting Information
- Supporting information for this article is available online at http://dx.doi.org.accesdistant.sorbonne-universite.fr/10.1055/s-0034-1380696.
- Supporting Information
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References
- 1a Müller TJ. J, D’Souza DM. Pure Appl. Chem. 2008; 80: 609
- 1b Glushkov VA, Tolstikov AG. Russ. Chem. Rev. 2008; 77: 137
- 1c Orru RV. A, de Greef M. Synthesis 2003; 1471
- 1d Ramón DG, Yus M. Angew. Chem. Int. Ed. 2005; 44: 1602
- 2 Kouznetsov VV. Tetrahedron 2009; 65: 2721
- 3 Povarov LS. Russ. Chem. Rev. 1967; 36: 656
- 4 Tolstikov AG, Savchenko RG, Nedopekin DV, Afon’kina SR, Lukina ЕS, Оdinokov VN. Russ. Chem. Bull. 2011; 60: 160
- 5a Mellor JM, Merriman GD, Riviere P. Tetrahedron Lett. 1991; 32: 7103
- 5b Temme O, Laschat S, Fröhlich R, Wibbeling B, Heinze J, Hauser P. J. Chem. Soc., Perkin Trans. 2 1997; 2083
- 5c Temme O, Laschat S. J. Chem. Soc., Perkin Trans. 1 1995; 125
- 5d Yadav JC, Reddy BV. S, Chetia L, Srinivasulu G, Kunwar AC. Tetrahedron Lett. 2005; 46: 1039
- 5e Powell DA, Batey RA. Tetrahedron Lett. 2003; 44: 7569
- 6 Linkert F, Laschat S, Kotila S, Fox T. Tetrahedron 1996; 52: 955
- 7 Grieco PA, Bahsas A. Tetrahedron Lett. 1988; 29: 5855
- 8 Tolstikov AG, Savchenko RG, Lukina ЕS, Afon’kina SR, Nedopekin DV, Khalilov LM, Оdinokov VN. Russ. Chem. Bull. 2013; 62: 2377
- 9 Sheldrick GM. SHELX97 [Includes SHELXS97, SHELXL97 and CIFTAB]: Programs for Crystal Structure Analysis (Release 97-2). Institüt für Anorganische Chemie der Universität Göttingen; Germany: 1998
- 10 Crystallographic data for compounds 3a, 4a, 4b, and 5 have been deposited with the accession numbers CCDC 985712, 1002452, 943834, and 985713, respectively, and can be obtained free of charge from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK, Fax: +44(1223)336033, E-mail: deposit@ccdc.cam.ac.uk, Web site: www.ccdc.cam.ac.uk/conts/retrieving.html.
-
References
- 1a Müller TJ. J, D’Souza DM. Pure Appl. Chem. 2008; 80: 609
- 1b Glushkov VA, Tolstikov AG. Russ. Chem. Rev. 2008; 77: 137
- 1c Orru RV. A, de Greef M. Synthesis 2003; 1471
- 1d Ramón DG, Yus M. Angew. Chem. Int. Ed. 2005; 44: 1602
- 2 Kouznetsov VV. Tetrahedron 2009; 65: 2721
- 3 Povarov LS. Russ. Chem. Rev. 1967; 36: 656
- 4 Tolstikov AG, Savchenko RG, Nedopekin DV, Afon’kina SR, Lukina ЕS, Оdinokov VN. Russ. Chem. Bull. 2011; 60: 160
- 5a Mellor JM, Merriman GD, Riviere P. Tetrahedron Lett. 1991; 32: 7103
- 5b Temme O, Laschat S, Fröhlich R, Wibbeling B, Heinze J, Hauser P. J. Chem. Soc., Perkin Trans. 2 1997; 2083
- 5c Temme O, Laschat S. J. Chem. Soc., Perkin Trans. 1 1995; 125
- 5d Yadav JC, Reddy BV. S, Chetia L, Srinivasulu G, Kunwar AC. Tetrahedron Lett. 2005; 46: 1039
- 5e Powell DA, Batey RA. Tetrahedron Lett. 2003; 44: 7569
- 6 Linkert F, Laschat S, Kotila S, Fox T. Tetrahedron 1996; 52: 955
- 7 Grieco PA, Bahsas A. Tetrahedron Lett. 1988; 29: 5855
- 8 Tolstikov AG, Savchenko RG, Lukina ЕS, Afon’kina SR, Nedopekin DV, Khalilov LM, Оdinokov VN. Russ. Chem. Bull. 2013; 62: 2377
- 9 Sheldrick GM. SHELX97 [Includes SHELXS97, SHELXL97 and CIFTAB]: Programs for Crystal Structure Analysis (Release 97-2). Institüt für Anorganische Chemie der Universität Göttingen; Germany: 1998
- 10 Crystallographic data for compounds 3a, 4a, 4b, and 5 have been deposited with the accession numbers CCDC 985712, 1002452, 943834, and 985713, respectively, and can be obtained free of charge from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK, Fax: +44(1223)336033, E-mail: deposit@ccdc.cam.ac.uk, Web site: www.ccdc.cam.ac.uk/conts/retrieving.html.













