Synlett 2017; 28(03): 316-322
DOI: 10.1055/s-0036-1588116
letter
© Georg Thieme Verlag Stuttgart · New York

Microwave-Assisted Tandem Reactions towards a New Synthesis of Cyclohepta[b]chromene-9,11-diones

Joana L. C. Sousa
Department of Chemistry & QOPNA, University of Aveiro, 3810-193 Aveiro, Portugal   Email: [email protected]
,
Artur M. S. Silva*
Department of Chemistry & QOPNA, University of Aveiro, 3810-193 Aveiro, Portugal   Email: [email protected]
› Author Affiliations
Further Information

Publication History

Received: 20 August 2016

Accepted after revision: 14 November 2016

Publication Date:
05 December 2016 (online)


Abstract

A microwave-assisted new synthesis of functionalized cyclohepta[b]chromene-9,11-diones has been described for the first time. The key step involves the reaction of (E)-3-bromo-2-styrylchromones with 1-(prop-1-en-2-yl)pyrrolidine and provides benzo[1,3]cyclopropa[1,2-b]chromene-4,5-diones by a tandem 1,6-conjugate addition/ Michael-initiated ring-closure/imine hydrolysis sequence. The second step involves an acid-catalyzed cyclopropane ring-expansion reaction of these polycyclic compounds to afford the expected cyclohepta[b]chromene-9,11-diones.

Supporting Information

 
  • References and Notes

  • 1 Gomes A, Freitas M, Fernandes E, Lima JL. F. C. Mini-Rev. Med. Chem. 2010; 10: 1
    • 2a Kelkar AS, Letcher RM, Cheung K.-K, Chiu K.-F, Brown GD. J. Chem. Soc., Perkin Trans. 1 2000; 3732
    • 2b Patoilo DT, Silva AM. S, Pinto DC. G. A, Santos CM. M, Tomé AC, Cavaleiro JA. S. Tetrahedron Lett. 2012; 53: 2722
    • 3a Silva EM. P, Silva AM. S, Cavaleiro JA. S. Synlett 2011; 2740
    • 3b Silva EM. P, Grenda K, Cardoso IN, Silva AM. S. Synlett 2013; 24: 2375
    • 3c Pinto DC. G. A, Silva AM. S, Cavaleiro JS, Foces-Foces C, Llamas-Saiz AL, Jagerovic N, Elguero J. Tetrahedron 1999; 55: 10187
  • 4 Pinto DC. G. A, Silva AM. S, Almeida LM. P. M, Cavaleiro JA. S, Lévai A, Patonay T. J. Heterocycl. Chem. 1998; 35: 217
  • 5 Ferreira JP. A, Silva VL. M, Elguero J, Silva AM. S. Tetrahedron 2013; 69: 9701
  • 6 Santos CM. M, Silva AM. S, Cavaleiro JA. S. Eur. J. Org. Chem. 2009; 2642
  • 7 Csaky AG, de la Herran G, Murcia MC. Chem. Soc. Rev. 2010; 39: 4080
  • 8 Talhi O, Brodziak-Jarosz L, Panning J, Orlikova B, Zwergel C, Tzanova T, Philippot S, Pinto DC. G. A, Paz FA. A, Gerhäuser C, Dick TP, Jacob C, Diederich M, Bagrel D, Kirsch G, Silva AM. S. Eur. J. Org. Chem. 2016; 965
    • 9a Silva EM. P, Silva AM. S. Synthesis 2012; 44: 3109
    • 9b Silva EM. P, Grenda K, Cardoso IN, Silva AM. S. Synlett 2013; 24: 2375
  • 10 Sousa JL. C, Talhi O, Mendes RF, Paz FA. A, Bachari K, Silva AM. S. Eur. J. Org. Chem. 2016; 3949
  • 11 de la Hoz A, Diaz-Ortiz A, Moreno A. Chem. Soc. Rev. 2005; 34: 164
    • 12a Pinto DC. G. A, Silva AM. S, Brito CM, Sandulache A, Carrillo JR, Prieto P, Díaz-Ortiz A, de la Hoz A, Cavaleiro JA. S. Eur. J. Org. Chem. 2005; 2973
    • 12b Albuquerque HM. T, Santos CM. M, Cavaleiro JA. S, Silva AM. S. Eur. J. Org. Chem. 2015; 4732
    • 12c Silva VL. M, Silva AM. S, Pinto DC. G. A, Elguero J, Cavaleiro JA. S. Eur. J. Org. Chem. 2009; 4468
  • 13 Gaspar A, Matos MJ, Garrido J, Uriarte E, Borges F. Chem. Rev. 2014; 114: 4960
  • 14 Ramesh P, Reddy NS, Venkateswarlu Y, Reddy MV. R, Faulkner DJ. Tetrahedron Lett. 1998; 39: 8217
  • 15 Nishizawa M, Inoue A, Hayashi Y, Sastrapradja S, Kosela S, Iwashita T. J. Org. Chem. 1984; 49: 3660
  • 16 Bentley R. Nat. Prod. Rep. 2008; 25: 118
  • 17 General Procedure for the Synthesis of Benzo[1,3]cyclopropa[1,2-b]chromene-4,5-diones 2a–c Pyrrolidine (8.3 μL, 0.099 mmol) was added to a solution of the appropriate (E)-3-bromo-2-styrylchromone 1ac (0.066 mmol) in acetone (1 mL) in a closed vessel. The mixture was heated at 100 °C under microwave irradiation (monomode apparatus) for 20 min. Then, the solvent was evaporated under reduced pressure, and the obtained residue was purified by preparative TLC using CH2Cl2 as eluent to give the desired products 2ac as an inseparable mixture of diastereomers: 2a (13.9 mg, 69%), 2b (15.7 mg, 71%), and 2c (11.4 mg, 51%). rel-(2S,4aR,4bR)- and rel-(2R,4aR,4bR)-2-Phenyl-2,3,4a,4b-tetrahydro-1H-benzo[1,3]cyclopropa[1,2-b]chromene-4,5-dione (2a) White solid. 1H NMR (500.13 MHz, CDCl3): aliphatic region: d1 : δ = 2.46–2.58 (m, 3 H, Hb-1 and H-3), 2.53 (d, J = 4.9 Hz, 1 H, H-4a), 2.83 (d, J = 4.9 Hz, 1 H, H-4b), 2.91 (ddd, J = 1.7, 6.2, 15.1 Hz, 1 H, Ha-1), 3.41–3.48 (m, 1 H, H-2) ppm; d2: δ = 2.41–2.47 (m, 1 H, H-3), 2.59 (d, J = 4.6 Hz, 1 H, H-4a), 2.69–2.77 (m, 3 H, H-1 and H-3), 2.97–3.04 (m, 1 H, H-2), 3.10 (d, J = 4.6 Hz, 1 H, H-4b) ppm; aromatic region: d1 and d2 : δ = 6.98–7.00 (m, 2 H, H-9), 7.07–7.14 (m, 2 H, H-7), 7.22–7.27 (m, 4 H, H-2′,6′), 7.28–7.32 (m, 2 H, H-4′), 7.36–7.40 (m, 4 H, H-3′,5′), 7.51–7.55 (m, 2 H, H-8), 7.88 and 7.89 (2 dd, J = 1.7, 7.9 Hz, 2 H, H-6) ppm. 13C NMR (125.77 MHz, CDCl3): δ = 31.5 (C-4a of d2), 31.8 (C-4a of d1), 33.9 (C-1 of d2), 34.1 (C-4b of d2), 34.5 (C-2 of d2), 38.6 (C-1 of d1), 40.9 (C-2 of d1), 41.6 (C-4b of d1), 42.8 (C-3 of d1), 44.6 (C-3 of d2), 67.7 (C-10a of d2), 70.0 (C-10a of d1), 117.8 (C-5a of d2), 117.87 and 117.88 (C-9), 118.4 (C-5a of d1), 122.69 and 122.73 (C-7), 126.6 and 126.7 (C-2′,6′), 127.1 and 127.3 (C-6), 127.48 and 127.52 (C-4′), 129.07 and 129.11 (C-3′,5′), 136.3 and 136.4 (C-8), 141.6 and 141.9 (C-1′), 156.3 and 156.4 (C-9a), 185.9 and 186.3 (C-5), 201.8 (C-4 of d2), 203.0 (C-4 of d1) ppm. MS (EI): m/z (%) = 305 (14) [M•+ + H]+, 304 (100) [M•+], 276 (32), 275 (11), 261 (28), 247 (21), 200 (20), 199 (17), 187 (26), 186 (73), 185 (14), 172 (75), 171 (54), 159 (41), 158 (39), 144 (49), 121 (35). HRMS (EI): m/z calcd for C20H16O3: 304.1099; found: 304.1101.
  • 18 General Procedure for the Synthesis of Cyclohepta[b]chromene-9,11-diones 3a–c The appropriate benzo[1,3]cyclopropa[1,2-b]chromene-4,5-dione 2ac (0.045 mmol) was refluxed in glacial acetic acid (1 mL) with a drop of sulfuric acid for 2 h. After this period, the reaction mixture was poured into ice and water. Then, this aqueous mixture was extracted with EtOAc (2 × 10 mL), and the obtained residue was purified by preparative TLC using a (9:1) mixture of CH2Cl2–EtOAc as eluent. Two fractions were obtained: 7-aryl-6,7,8,10-tetrahydrocyclohepta[b]chromene-9,11-diones 3ac (higher Rf value) in 55–73% yield and 6-aryl-2-(2-hydroxyphenyl)-6,7-dihydrobenzofuran-4(5H)-ones 6ac in 16–20% yield. 7-Phenyl-6,7,8,10-tetrahydrocyclohepta[b]chromene-9,11-dione (3a) Yield 8.4 mg (61%); white solid; mp 134–136 °C. 1H NMR (300.13 MHz, CDCl3): δ = 2.88–3.00 (m, 2 H, H-8), 3.21 (d, J = 6.9 Hz, 2 H, H-6), 3.63–3.72 (m, 1 H, H-7), 3.86 and 3.92 (ABq, J AB = 17.2 Hz, 2 H, H-10), 7.26–7.36 (m, 5 H, H-2′,3′,4′,5′,6′), 7.36–7.45 (m, 2 H, H-2 and H-4), 7.67 (td, J = 1.6, 7.8 Hz, 1 H, H-3), 8.25 (dd, J = 1.6, 7.9 Hz, 1 H, H-1) ppm. 13C NMR (75.47 MHz, CDCl3): δ = 38.0 (C-10), 39.4 (C-6), 41.1 (C-7), 49.1 (C-8), 115.4 (C-10a), 117.8 (C-4), 122.6 (C-11a), 125.3 (C-2), 126.2 (C-1), 126.5 (C-2′,6′), 127.4 (C-4′), 129.1 (C-3′,5′), 133.7 (C-3), 143.3 (C-1′), 155.9 (C-4a), 164.1 (C-5a), 176.2 (C-11), 207.2 (C-9) ppm. ESI-MS: m/z (%) = 305 (4) [M + H]+, 327 (100) [M + Na]+, 631 (16) [2M + Na]+. HRMS (EI): m/z calcd for C20H16O3: 304.1099; found: 304.1105. 2-(2-Hydroxyphenyl)-6-phenyl-6,7-dihydrobenzofuran-4(5H)-one (6a) Yield 2.7 mg (20%); white solid; mp 269–272 °C. 1H NMR (500.13 MHz, DMSO-d 6): δ = 2.57 (dd, J = 3.9, 16.2 Hz, 1 H, H-5), 2.91 (dd, J = 12.4, 16.2 Hz, 1 H, H-5), 3.25 (d, J = 8.0 Hz, 2 H, H-7), 3.62–3.68 (m, 1 H, H-6), 6.90 (ddd, J = 1.1, 7.3, 7.8 Hz, 1 H, H-5′), 6.98 (dd, J = 1.1; 8.2 Hz, 1 H, H-3′), 7.08 (s, 1 H, H-3), 7.18 (ddd, J = 1.7, 7.3, 8.2 Hz, 1 H, H-4′), 7.27 (tt, J = 1.3; 7.3 Hz, H-4′′), 7.34–7.38 (m, 2 H, H-3′′,5′′), 7.42–7.44 (m, 2 H, H-2′′,6′′), 7.68 (dd, J = 1.7, 7.8 Hz, 1 H, H-6′), 10.37 (s, 1 H, 2′-OH) ppm. 13C NMR (125.77 MHz, DMSO-d 6): δ = 30.3 (C-7), 40.3 (C-6), 44.5 (C-5), 104.5 (C-3), 116.1 (C-3′), 116.2 (C-1′), 119.3 (C-5′), 122.1 (C-3a), 125.2 (C-6′), 126.8 (C-4′′), 127.1 (C-2′′,6′′), 128.6 (C-3′′,5′′), 128.9 (C-4′), 143.1 (C-1′′), 150.9 (C-2), 153.8 (C-2′), 165.3 (C-7a), 192.6 (C-4) ppm. MS (EI): m/z (%) = 305 (10) [M•+ + H]+, 304 (64) [M•+], 200 (87), 173 (12), 172 (100), 171 (33), 121 (76). HRMS (EI): m/z calcd for C20H16O3: 304.1099; found: 304.1096.
  • 19 Hewitt RJ, Harvey JE. J. Org. Chem. 2010; 75: 955
  • 20 General Procedure for the Synthesis of Dimers 13 and 14 A solution of (E)-3-bromo-2-styrylchromone 1a (50 mg, 0.15 mmol) in acetone (5 mL) at r.t. was irradiated with a 500 W halogen lamp for 16 h. After this period, the solvent was evaporated to dryness, and the obtained residue was purified by preparative TLC using CH2Cl2 as eluent. Mixture of two Diastereomers dM and dm (64:36) of (E)-8a-Bromo-2-(3-bromo-4-oxo-4H-chromen-2-yl)-1-phenyl-2a-styryl-1,2,2a,8a-tetrahydro-8H-cyclobuta[b]chromen-8-one (13) Yield 17.5 mg (18%); white solid. 1H NMR (500.13 MHz, CDCl3): dM-13: δ = 4.72 (d, J = 12.4 Hz, 1 H, H-1), 5.20 (d, J = 12.4 Hz, 1 H, H-2), 6.75 (d, J = 15.8 Hz, 1 H, H-α), 7.16 (d, J = 15.8 Hz, 1 H, H-β), 7.52 (dd, J = 0.6, 8.5 Hz, 1 H, H-8′′), 7.66–7.73 (m, 2 H, H-5 and H-7′′), 7.86 (dd, J = 1.6, 7.9 Hz, H-7), 8.15 (dd, J = 1.4, 8.0 Hz, 1 H, H-5′′) ppm; dm-13 δ = 5.16 (d, J = 11.1 Hz, 1 H, H-1), 5.27 (d, J = 11.1 Hz, 1 H, H-2), 6.76 and 6.80 (ABq, J AB = 15.9 Hz, 2 H, H-α and H-β), 7.05 (dd, J = 0.6, 8.4 Hz, 1 H, H-4), 7.59 (ddd, J = 1.8, 7.2, 8.4 Hz, 1 H, H-5), 7.63–7.66 (m, 1 H, H-7′′), 8.06 (dd, J = 1.7, 7.9 Hz, 1 H, H-7), 8.26 (dd, J = 1.5, 8.0 Hz, 1 H, H-5′′) ppm; dM- and dm-13: δ = 7.16–7.47 (m, 26 H, H-4-dM, H-6, H-2′,3′,4′,5′,6′, H-6′′, H-8′′, H-2′′′,3′′′,4′′′,5′′′,6′′′) ppm. 13C NMR (125.77 MHz, CDCl3): dM-13: δ = 48.2 (C-2), 49.2 (C-1), 64.5 (C-8a), 85.3 (C-2a), 111.3 (C-3′′), 117.4 (C-8′′), 119.6 (C-4), 119.9 (C-7a), 121.9 (C-4′′a), 123.5 (C-α), 123.7 (C-6), 126.1 (C-6′′), 126.6 (C-5′′), 126.8 (C-2′′′,6′′′), 127.31 (C-2′,6′), 128.15 and 128.4 (C-4′,4′′′), 128.17 (C-7), 128.66 (C-3′′′,5′′′), 128.9 (C-3′,5′), 133.0 (C-β), 133.4 (C-1′), 134.22 (C-7′′), 135.7 (C-1′′′), 137.5 (C-5), 155.2 (C-8′′a), 156.8 (C-3a), 158.68 (C-2′′), 172.0 (C-4′′), 184.6 (C-8) ppm; dm-13: δ = 47.3 (C-1), 51.7 (C-2), 69.6 (C-8a), 88.9 (C-2a), 112.4 (C-3′′), 117.8 (C-8′′), 118.20 (C-7a), 118.23 (C-4), 122.1 (C-4′′a), 123.0 (C-6), 126.0 (C-6′′), 126.4 (C-α), 126.5 (C-5′′), 127.1 (C-2′′′,6′′′), 127.27 and 127.4 (C-4′,4′′′), 127.6 (C-2′,6′), 128.6 and 128.69 (C-3′,5′,3′′′,5′′′), 128.8 (C-7), 133.6 (C-β), 134.17 (C-7′′), 135.5 (C-1′′′), 136.1 (C-1′), 137.4 (C-5), 155.5 (C-8′′a), 158.74 (C-2′′), 159.8 (C-3a), 172.4 (C-4′′), 185.4 (C-8) ppm. 2,2′-(3,4-Diphenylcyclobutane-1,2-diyl)bis(3-bromo-4H-chromen-4-one) (14) Yield 15.9 mg (16%); white solid; mp 280–282 °C. 1H NMR (300.13 MHz, CDCl3): δ = 4.95 (dd, J = 7.4, 10.2 Hz, 2 H, H-3′′,4′′), 5.29 (dd, J = 7.4, 10.2 Hz, 2 H, H-1′′,2′′), 7.07 (t, J = 7.3 Hz, 2 H, H-4′′′,4′′′′), 7.19 (t, J = 7.6 Hz, 4 H, H-3′′′,5′′′,3′′′′,5′′′′), 7.31–7.40 (m, 8 H, H-6,6′,8,8′,2′′′,6′′′,2′′′′,6′′′′), 7.64 (ddd, J = 1.6, 7.3, 8.6 Hz, 2 H, H-7,7′), 8.13 (dd, J = 1.6, 8.0 Hz, 2 H, H-5,5′) ppm. 13C NMR (75.47 MHz, CDCl3): δ = 43.3 (C-3′′,4′′), 45.9 (C-1′′,2′′), 111.3 (C-3,3′), 117.3 (C-8,8′), 121.6 (C-10,10′), 125.8 (C-6,6′), 126.4 (C-5,5′), 126.9 (C-2′′′,6′′′,2′′′′,6′′′′), 127.4 (C-4′′′,4′′′′), 128.7 (C-3′′′,5′′′,3′′′′,5′′′′), 134.0 (C-7,7′), 137.3 (C-1′′′,1′′′′), 154.9 (C-9,9′), 163.3 (C-2,2′), 172.0 (C-4,4′) ppm. ESI-MS: m/z (%) = 653 (79Br, 43) [M + H]+, 655 (81Br, 83) [M + H]+, 675 (79Br, 53) [M + Na]+, 677 (81Br, 100) [M + Na]+, 691 (79Br, 17) [M + K]+, 693 (81Br, 32) [M + K]+. ESI-HRMS: m/z calcd for [C34H22 79Br2O4 + H]+: 652.9963; found: 652.9955.