HETEROCYCLES

Short Paper | Special issue | Vol. 86, No. 2, 2012, pp. 1541-1547
Received, 29th June, 2012, Accepted, 8th August, 2012, Published online, 24th August, 2012.
DOI: 10.3987/COM-12-S(N)75

■ Synthesis of a Novel Non-Benzenoid Quinone, 3,10-Dihydro-2,4-dimethyl-7,13-methanocyclohepta[11]annulene-3,10-dione, from 8H-7,9-Bis(methoxycarbonyl)-5,11-methano[11]annuleno[c]furan-8-one

Shigeyasu Kuroda,* Naoko Matsumoto, Yanmei Zhang, Ryuta Miyatake, Yurie Fujiwara, and Mitsunori Oda*

Department of Chemistry, Faculty of Science, Shinshu University, Asahi, Matsumoto 390-8621, Japan

Abstract

8H-7,9-Bis(methoxycarbonyl)-5,11-methano[11]anuleno[c]furan- 8-one (3) undergoes [4+3] cycloaddition with an oxyallyl species generated from 2,4-dibromo-3-pentanone in the presence of KI and copper, followed by dehydration in fluorosulfuric acid to give cyclohepta[11]annulenedione diester 9. After hydrolysis of the ester groups, decarboxylation yielded the title quinone 6. The 1H NMR spectrum of 6 in D2SO4 indicates generation of its protonated dicationic species.

We have previously found the efficient synthesis of 6H-cyclohepta[c]furan-5,7-dicarbaldehyde (2) from furan-3,4-dicarbaldehyde (1) by aldol condensation with pentanedial and developed a novel synthetic method for brigded [11]annulenones, 8H-7,9-bis(methoxycarbonyl)-5,11-methano[11]anuleno[c]furan-8-one (3) and its nor-ester compound 4 from 2. We also disclosed [4+2] cycloaddition of 3 and 4 with dimethyl acetylenedicarboxylate (DMAD) at their furan ring to present potentiality for extension of their carbon framework.1 Later, we reported that the furan moiety of 2, after modification of their formyl groups, undergoes [4+3] cycloaddition with an oxyallyl species2 generated from 2,4-dibromo-3-pentanone and, then, was converted into a tropone-annulated methano[10]annulene derivative 5.3 These results indicate that the formyl groups and the furan functionallity of compound 2 are

advantageous to elaborate π-bond-extended methano-bridged compounds. In this short paper, we describe synthesis of a new non-benzenoid quinone4 of bridged cyclohepta[11]annulene, 3,10-dihydro-2,4-dimethyl-7,13-methanocyclohepta[11]anulene-3,10-dione (6), based on the reactivity of 2, and its protonation.

The synthesis of 6 from 3 is shown in Scheme 3. Compound 3 undergoes [4+3] cycloaddition with an oxyallyl reagent generated from 2,4-dibromo-3-pentanone in the presence of KI and copper. The product was isolated as a mixture of two inseparable stereoisomers in 95% yield. The 1H NMR spectrum of this mixture indicates that it constitutes two stereoisomers in ratio of 4:1. Signals for the two methyl groups on the seven-membered ring appear to be equivalent for both stereoisomers and those of the two methyl groups of the esters do in the same way, suggesting that these isomers are symmetrical through a plane containing bridging methylene carbon and hydrogens. Since both isomers have coupling constants of 4.4 Hz between adjacent methine protons on the seven-membered ring, relative stereochemistry between the methyl groups and the ether group is assigned as trans (7 and 8) for both isomers, based on

previously analyzed NMR data by Hoffmann et al.6 However, the stereochemical relationship between the oxa and methano bridges for each product is obscure from these spectral data. Dehydration of a mixture of 7 and 8 in fluorosulfuric acid gave diketo-diester 9 in 58% yield. Finally, two ester groups in 9 were removed by hydrolysis in KOH/MeOH and subsequent thermal decarboxylation in the presence of copper metal to give the title compound 6 in 40% yield. Compound 6 was isolated as stable yellow microcrystals. Its structure was confirmed by spectroscopic analysis. Typical features are as follows; the carbonyl and C=C absorption bands in the IR spectrum were observed at 1576 and 1608 cm–1, respectively.7 The bridging methylene protons in the 1H NMR spectrum in CDCl3 resonate at 0.53 and 2.18 ppm with a coupling constant of 11.6 Hz.8 The long-wave absorption in the UV-vis spectrum of 6 in CH2Cl2 was found at 438 nm. Generation of the cationic species was studied by 1H NMR analysis. The chemical shifts in the 1H NMR spectrum of 6 in CDCl3 and acid media are shown in Scheme 4, accompanied with those of 31 and 4,9-methano[11]anulenone (11).9 As seen in heptalenediones,5,10 sufficient duplicated protonation of 6 was not observed in CF3CO2D, probably because of retardation in the second protonation. Acidity of D2SO4 was found strong enough to generate the dicationic species.11,12 The 1H NMR spectrum in D2SO4 shows clear a down-field shift of the peripheral ring protons and a up-field shift of the bridging methylene protons, indicating that 6D22+ is diatropic and exist as a full conjugated 14π-electronic dicationic structure. Beside shift values for all protons, changes of average shifts of the bridging and peripheral protons are also shown in Scheme 4. The magnitude of these shifts in 6 is greater than that seen in 3. While the down-field shift of the peripheral protons for 6 is greater than that of 11, the up-field shift of the bridging methylene protons for 6 is less than that for 11, probably because of a deshielding effect by the neighboring tropylium ring.

We have demonstrated that the title cyclohepta[11]annulenedione 6 can be synthesized from 3 and protonation of 6 generates diatropic dicationic species 6D22+. As far as we know, 6D22+ is the first example of a 14π-electronic dicationic structure having a methano-bridged [7]annuleno[11]annulene system. Completion of the synthesis of 6 in this study and our previous syntheses of 4 and 5 through cyclization using two formyl groups and the furan moiety prove importance of 2 as a versatile synthetic precursor for bridged annulenes and annulenones.

EXPERIMENTAL
Melting points were measured on a Yanaco MP-3. IR spectra were recorded on a Perkin-Elmer Spectrum RX 1 spectrometer. UV spectra were measured on a Shimadzu UV-1600 spectrometer. 1H and 13C NMR spectra were recorded with tetramethylsilane as internal standard on a JEOL α400 NMR instrument. Mass spectra were measured on a JMS-700 mass spectrometer. Column chromatography was done with Merck Kieselgel 60 Art 7734. Compound 3 was prepared by the previously reported method.1
[4+3] Cycloaddition reaction of 3 with 2,4-dibromo-3-pentanone in the presence of KI and copper
A mixture of KI (452 mg, 2.76 mM) and copper powder (177 mg, 2.76 mM) was charged in a 50 mL three-necked flask and heated under vacuumed at 150 ˚C on an oil bath for 3 h. After being cooled to room temperature, the flask was fitted with a condenser and dropping funnel, and 2,4-dibromo-3-pentanone (1,11 g, 4.60 mM), 3 (300 mg, 0.920 mM), and 30 mL of dry MeCN was added to the flask. This mixture was refluxed for 2 h under nitrogen atmosphere. Solids were removed by filtration and the filtrate was poured into 40 mL of water and extracted with CH2Cl2 (30 mL x 3). The combined organic layer was washed with brine and was dried over MgSO4. The solvent was removed and the residue was purified by silica gel column chromatography with AcOEt/Hexane (20/80) to give 395 mg (95% yield) of a mixture of 7 and 8 (4:1) as yellow solids. Mp 85–98 ˚C. 1H NMR (CDCl3) of the major stereoisomer in the mixture, δ = 8.04 (s, 2H), 7.19 (s, 2H), 5.26 (d, J = 4.4 Hz, 2H), 3.85 (s, 6H), 3.14 (qd, J = 7.2, 4.4 Hz, 2H), 2.03 (d, J = 12.0 Hz, 1H), 0.93 (d, J = 7.2 Hz, 6H), –0.16 (d, J = 12.0 Hz, 1H) ppm; 13C NMR (CDCl3) of the major stereoisomer in the mixture, δ = 207.5, 191.9, 164.3, 145.6, 139.9, 125.3, 123.8, 116.5, 86.5, 52.6, 50.7, 32.9, 9.8 ppm; 1H NMR (CDCl3) of the minor stereoisomer in the mixture, δ = 8.00 (s, 2H), 7.09 (s, 2H), 5.39 (d, J = 4.4 Hz, 2H), 3.85 (s, 6H), 3.25 (qd, J = 7.2, 4.4 Hz, 2H), 2.10 (d, J = 12.0 Hz, 1H), 1.21 (d, J = 7.2 Hz, 6H), 0.12 (d, J = 12.0 Hz, 1H) ppm; 13C NMR (CDCl3) of the minor stereoisomer in the mixture, δ = 207.0, 192.4, 164.3, 145.6, 140.0, 126.3, 123.0, 119.7, 84.0, 52.6, 49.5, 31.9, 9.8 ppm; IR (KBr) of the mixture, νmax = 1712s, 1698vs, 1691vs, 1681vs 1574m, 1360s, 1282s, 1236s, 1282s, 755s cm–1; UV-vis (CH2Cl2) of the mixture, λmax = 260 (log ε = 4.75), 302 (5.00), 377 (4.18) nm; MS (70 eV) of the mixture, m/z (rel int) = 410 (M+, 100), 353 (65), 326 (9), 267 (9), 239 (9), 168 (17), 152 (9). HRMS m/z Calcd for C23H22O7 (M+) 410.1366, found 410.1360.
3,10-Dihydro-9,11-bis(methoxycarbonyl)-2,4-dimethyl-7,13-methanocyclohepta[11]anulene-3,10-dione (9)
To a solution of a mixture of 7 and 8 (705 mg, 1.72 mM) in 10 mL of CH2Cl2 at 0 ˚C was added dropwise 1.72 g (17.2 mM) of fluorosulfuric acid and the mixture was stirred at the same temperature for 2 h. Then, the resulted reddish brown mixture was poured into 100 mL of water and was extracted with CH2Cl2 (30 mL x 3). The combined organic layer was washed with a saturated aqueous NaHCO3 solution and brine. After dryness over MgSO4, the solvent was removed and the residue was purified by silica gel column chromatography with AcOEt/Hexane (25/75) to give 391 mg (58% yield) of 9 as yellow powder. Mp 275–277˚C. 1H NMR (CDCl3), δ = 7.89 (s, 2H), 7.62 (s, 2H), 7.14 (s, 2H), 3.86 (s, 6H), 2.55 (d, J = 13.0 Hz, 1H), 2.38 (s, 6H), 0.58 (d, J = 13.0 Hz, 1H) ppm; 13C NMR (CDCl3) δ = 193.7, 187.2, 164.4, 145.2, 140.5, 139.0, 138.0, 134.5, 127.9, 120.0, 52.9, 30.7, 23.5 ppm; IR (ART) νmax = 1725s, 1709s, 1665m, 1609m, 1593s, 1582m, 1432m, 1267s, 1223s cm–1; UV-vis (CH2Cl2) λmax = 260 (log ε = 4.75), 302 (5.00), 377 (4.18) nm; MS (70 eV) m/z (rel int) = 392 (M+, 28), 364 (18), 336 (100), 305 (24), 277 (20), 202 (15). HRMS m/z Calcd for C23H20O6 (M+) 392.1260, found 392.1268.
3,10-Dihydro-2,4-dimethyl-7,13-methanocyclohepta[11]anulene-3,10-dione (6)
To a solution of 9 (100 mg, 0.255 mM) in 20 mL of MeOH and 1 mL of water was added 286 mg (0.510 mM) of potassium hydroxide. The mixture was refluxed on an oil bath for 2 h. Then, the resulted mixture was poured into 30 mL of 1M HCl and was extracted with EtOAc (20 mL x 3). The combined organic layer was washed with water and brine. After dryness over MgSO4, the solvent was removed and the residue was resolved in 5 mL of DMF. To this solution was added 32.6 mg (2.55 mM) of copper powder and the suspension was refluxed for 2.5 h. After removal of solids by filtration, the filtrate was mixed with 50mL of water and was extracted with AcOEt (20 mL x 3). The combined organic layer was washed with water and brine. After dryness over MgSO4, the solvent was removed and the residue was purified by silica gel column chromatography with AcOEt/Hexane (20/80) to give 28.1 mg (40% yield) of 6 as yellow microcrystals. Mp 228–229 ˚C. 1H NMR (CDCl3) δ = 7.66 (s, 2H), 7.24 (d, J = 12.4 Hz, 2H), 7.00 (s, 2H), 6.20 (d, J = 12.4 Hz, 2H), 2.36 (s, 6H), 2.18 (d, J = 11.6 Hz, 1H), 0.53 (d, J = 11.6 Hz, 1H) ppm; 13C NMR (CDCl3) δ = 194.4, 187.3, 144.0, 138.8, 138.7. 137.0. 130.3, 130.2, 127.7, 33.5, 23.5 ppm; IR (ART) νmax = 1608m, 1576s cm–1; UV-vis (CH2Cl2) λmax = 238 (log ε = 4.37), 250 (4.38), 321 (5.10), 367 (4.34), 438 (3.37) nm; MS (70 eV) m/z (rel int) = 276 (M+, 48), 220 (100), 219 (36), 205 (64), 189 (21). HRMS m/z Calcd for C19H16O2 (M+) 276.1150, found 276.1155.

References

1. Y. Zhang, N. Takezawa, Y. Horino, A. Takai, Y. Tsuji, R. Miyatake, M. Oda, and S. Kuroda, Heterocycles, 2009, 77, 241. CrossRef
2. H. M. R. Hoffmann, Angew. Chem., Int. Ed. Engl., 1970, 12, 819; CrossRef R. Noyori and Y. Hayakawa, Org. React., 1983, 29, 168.
3. S. Kuroda, N. Matsumoto, Y. Zhang, T. Abe, Y. Horino, Y. Fujiwara, and M. Oda, Heterocycles, 2012, 84, 275. CrossRef
4. For review articles on non-benzenoid quinones, see followings; a) R. West and J. Niu, 'Nonbenzenoid Aromatics,' Vol. 1, ed. by J. P. Snyder, Academic Press, Inc., New york and London, 1969, Ch. 16, pp. 311-345; b) T. A. Turney, 'The Chemistry of the Quinonoid Compounds,' Part 2, ed. by S. Patai, John Wiley & Sons, London-NewYork-Sydney-Tranto, 1974, Ch. 16, pp. 857–875; c) A. T. Balaban, M. Banciu, and V. Ciorba,, 'Annulenes, Benzo-, Hetero-, Homo-Derivatives and their Valence Isomers,' CRC Press, Boka Raton, 1987, Vol. III, Ch. 9, pp. 106–115; d) M. Nakagawa, 'The Chenistry of Annulenes,' Osaka Univ. Press, Osaka, 1996, 1974, Ch. 8 (Annulenediones), pp. 413–433.
5. For our related synthesis of 2,4-dimethylheptalene-3,8-dione from 5H-cyclohepta[c]fura-5-one, see following; K. Kato, M. Oda, S. Kuroda, N. Morita, and T. Asao, Chem. Lett., 1979, 8, 43. CrossRef
6. H. M. R. Hoffmann, K. E. Clemens, and R. H. Smithers, J. Am. Chem. Soc., 1972, 94, 3940. CrossRef
7. Two peaks for the two carbonyl groups were not observed; Expansion of the IR spectrum of 6 in a range between 1500–1700 cm–1 shows only the two C=O and C=C absorption peaks. These C=O and C=C absorptions are resemble to those of tropone itself (νC=O at 1570 cm–1 and νC=C at 1594 cm–1); K. Krebs and B. Schrader, Ann., 1967, 709, 46.
8. Assignment of bridging methylene protons in these annulenones were made by W-letter type long-range couplings with peripheral hydrogens.
9. a) W. Grimme, J. Reisdorff, W. Hünemann, and E. Voge, J. Am. Chem. Soc., 1970, 92, 6335; CrossRef b) T. Uehara and A. Ichida, Bull. Chem. Soc. Jpn., 1980, 53, 3375. CrossRef
10. S. Kuroda and T. Asao, Tetrahedron lett., 1977, 18, 289. CrossRef
11. The solution of 6 in D2SO4 appeared red, having λmax = 242 (log ε = 4.27), 279 (3.92), 361 (4.89), 469 (3.90) nm.
12. Compound can be recovered from the D2SO4 solution by neutralization with NaHCO3 and subsequent extraction with CH2Cl2.