Download PDF
Synlett 2012; 23(6): 867-872
DOI: 10.1055/s-0031-1290304
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of 1-Indanonyl Oxepanes

Meng-Yang Chang*
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C., Fax: +886(7)3125339   Email: mychang@kmu.edu.tw
,
Nien-Chia Lee
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C., Fax: +886(7)3125339   Email: mychang@kmu.edu.tw
› Author Affiliations
Further Information

Publication History

Received: 20 December 2011

Accepted after revision: 25 January 2012

Publication Date:
28 February 2012 (online)

    Permissions and Reprints All articles of this category


Abstract

A variety of 1-indanonyl oxepanes with the novel structure of indanonyl oxepanes was prepared from reaction of hydroxybenzaldehydes via a series of reasonable transformations, including the regioselective PhBCl2-mediated allylation (or Claisen rearrangement), one-pot reaction of ring-closing metathesis and the Wittig olefination, hydrogenation, and the Friedel–Crafts intramolecular cyclization.

Key words

heterocycles - metalation - metathesis - Wittig reaction - fused ring systems
 

  • References and Notes

    • 6a Aono T, Kishimoto S, Araki Y, Noguchi S. Chem. Pharm Bull. 1978; 26: 1776
      CrossrefSearch in Google Scholar
    • 6b Schuler G, Gorls H, Boland W. Eur. J. Org. Chem. 2001; 1663
    • 6c Girijia T, Shanker PS, Subba RaoG. S. R. J. Chem. Soc., Perkin Trans. 1 1991; 1467
    • 6d Lauchli R, Schuler G, Boland W. Phytochemistry 2002; 61: 807
      CrossrefSearch in Google Scholar
  • 8 Chattopadhyay SK, Biswas T, Maity S. Synlett 2006; 2211
    Thieme Connect
  • 9 Tsai J.-C, Li S.-R, Chen L.-Y, Chen PY, Jhong JY, Shu C.-J, Lo Y.-F, Lin C.-N, Wang E.-C. J. Chin. Chem. Soc. 2008; 55: 1317
    Search in Google Scholar

    • For Friedel–Crafts acylation reaction, see:

    • 12a Heaney H In Comprehensive Organic Synthesis. Vol. 2. Trost BM, Fleming I. Pergamon Press; Oxford: 1991: 733
      CrossrefSearch in Google Scholar
    • 12b Olah GA. Friedel–Crafts Chemistry. John Wiley and Sons; New York: 1973
      Search in Google Scholar
    • 12c For reviews on the intramolecular Friedel–Crafts acylation reaction, see: Heaney H. In Comprehensive Organic Synthesis. Vol. 2. Trost BM, Fleming I. Pergamon Press; Oxford: 1991: 753
      CrossrefSearch in Google Scholar
    • 12d Sethna S In Friedel–Crafts and Related Reactions. Vol. 3. Olah GA. Interscience; New York: 1964: 911
      Search in Google Scholar
  • 13 CCDC 846976 (1a), 845967 (1c), 853005 (1f), 853004 (1g), and 845966 (7) contain the supplementary crystallographic data for this paper. This data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html [or from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44(1223)336033; e-mail: deposit@ccdc.cam.ac.uk ]
  • 14 Representative Synthetic Transformation of Skeleton 1 from 5 A solution of 5 (0.4 mmol) and aq NaOH (6 M, 5 mL) in THF (10 mL) was refluxed for 6 h. The reaction was traced by TLC until 5 was completely consumed. The reaction solution was cooled to r.t. and concentrated until one third of the solution remained. The remained solution was extracted with EtOAc (3 × 10 mL). The aqueous phase was cooled in an ice-bath and acidified by adding concentrated aq HCl to pH 2. The aqueous solution was extracted with EtOAc (3 × 20 mL), and the extracts were washed with brine. The combined organic layers were washed with brine, dried, filtered, and evaporated to afford a crude acid product under reduced pressure. Without purification, PPA (3 mL) was added to a solution of the crude acid product in CH2Cl2 (5 mL) at r.t. The reaction mixture was stirred at r.t. for 4 h. Saturated aq NaHCO3 (10 mL) was added to the reaction mixture, and the residue was extracted with CH2Cl2 (3 × 30 mL). The combined organic layers were washed with brine, dried, filtered, and evaporated to afford the crude product under reduced pressure. Purification on silica gel (hexanes–EtOAc = 3:1) afforded skeleton 1. Representative Data for Compound 1a Colorless solid; mp 135–136 °C (recrystallized from hexanes and EtOAc). ESI-HRMS: m/z ] calcd for C13H15O2 203.1072 [M+ + 1; found: 203.1073. 1H NMR (400 MHz, CDCl3): δ = 7.54 (d, J = 8.0 Hz, 1 H), 6.98 (d, J = 8.0 Hz, 1 H), 4.10 (dd, J = 5.2, 5.6 Hz, 2 H), 3.02 (t, J = 5.6 Hz, 2 H), 2.85–2.82 (m, 2 H), 2.69–2.66 (m, 2 H), 2.05–1.99 (m, 2 H), 1.82–1.76 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 205.94, 166.03, 155.93, 132.40, 131.52, 122.75, 121.61, 77.31, 73.29, 36.48, 31.60, 27.83, 24.88. Anal. Calcd for C13H14O2: C, 77.20; H, 6.98. Found: C, 77.51; H, 7.34. Single-crystal X-ray diagram shows that the crystal of compound 1a was grown by slow diffusion of EtOAc into a solution of compound 1a in CH2Cl2 to yield colorless prism. The compound crystallizes in the triclinic crystal system, space group P-1, a = 8.4928(2) Å, b = 10.5935(2) Å, c = 12.4192(2) Å, V = 1032.67(4) Å3, Z = 4, d calcd = 1.301 g/cm3, F(000) = 432, 2θ range 1.69–26.40°; R indices (all data): R1 = 0.0938, wR2 = 0.1850. Compound 1c Colorless solid; mp 126–127 °C (recrystallized from hexanes and EtOAc). ESI-HRMS: calcd for C14H17O3 [M+ + 1]: 233.1178; found: 233.1182. 1H NMR (400 MHz, CDCl3): δ = 7.06 (s, 1 H), 4.11 (dd, J = 5.2, 5.6 Hz, 2 H), 3.83 (s, 3 H), 2.94–2.92 (m, 2 H), 2.82–2.79 (m, 2 H), 2.63–2.60 (m, 2 H), 2.04–1.98 (m, 2 H), 1.79–1.73 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 206.28, 155.54, 151.99, 147.87, 132.36, 131.62, 102.86, 73.48, 55.94, 36.12, 31.50, 27.90, 24.54, 24.32; Anal. Calcd for C14H16O3: C, 72.39; H, 6.94. Found: C, 72.68; H, 7.23. Single-crystal X-ray diagram shows that the crystal of compound 1c was grown by slow diffusion of EtOAc into a solution of compound 1c in CH2Cl2 to yield colorless prism. The compound crystallizes in the triclinic crystal system, space group P-1, a = 8.4193(10) Å, b = 8.6260(10) Å, c = 9.7658(12) Å, V = 593.29(12) Å3, Z = 2, d calcd = 1.300 g/cm3, F(000) = 248, 2θ range 2.25–26.38°; R indices (all data): R1 = 0.0978, wR2 = 0.1994. Compound 1f Colorless solid; mp 75–76 °C (recrystallized from hexanes and EtOAc). ESI-HRMS: m/z calcd for C13H15O2 [M+ + 1]: 203.1072; found: 203.1074. 1H NMR (400 MHz, CDCl3): δ = 7.32 (s, 1 H), 7.24 (s, 1 H), 4.02–3.98 (m, 2 H), 3.05–3.02 (m, 2 H), 2.89–2.86 (m, 2 H), 2.68–2.65 (m, 2 H), 2.00–1.95 (m, 2 H), 1.77–1.72 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 206.36, 160.07, 150.58, 144.26, 136.50, 127.76, 115.29, 73.93, 36.89, 34.82, 32.07, 25.98, 25.10. Anal. Calcd for C13H14O2: C, 77.20; H, 6.98. Found: C, 77.39; H, 7.14. Single-crystal X-ray diagram shows that the crystal of compound 1f was grown by slow diffusion of EtOAc into a solution of compound 1f in CH2Cl2 to yield colorless prism. The compound crystallizes in the monoclinic crystal system, space group P1 21/c 1, a = 20.6470(13) Å, b = 6.1783(4) Å, c = 17.7204(10) Å, V = 2093.3(2) Å3, Z = 8, d calcd = 1.283 g/cm3, F(000) = 864, 2θ range 1.06–26.71°; R indices (all data): R1 = 0.0883, wR2 = 0.1083. Compound 1g Colorless solid; mp 107–108 °C (recrystallized from hexanes and EtOAc). ESI-HRMS: m/z calcd for C13H15O2 [M+ + 1]: 203.1072; found: 203.1076. 1H NMR (400 MHz, CDCl3): δ = 7.17 (s, 2 H), 4.00–3.98 (m, 2 H), 3.46–3.43 (m, 2 H), 2.99–2.96 (m, 2 H), 2.68–2.65 (m, 2 H), 2.00–1.95 (m, 2 H), 1.74–1.67 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 207.91, 160.25, 150.89, 135.42, 134.41, 127.42, 124.38, 73.42, 37.69, 32.17, 24.90, 24.55, 24.20. Anal. Calcd for C13H14O2: C, 77.20; H, 6.98. Found: C, 77.41; H, 6.76. Single-crystal X-ray diagram shows that the crystal of compound 1g was grown by slow diffusion of EtOAc into a solution of compound 1g in CH2Cl2 to yield colorless prism. The compound crystallizes in the monoclinic crystal system, space group P1 21/n 1, a = 9.0400(9) Å, b = 8.6174(9) Å, c = 13.6389(14) Å, V = 1044.01(18) Å3, Z = 4, d calcd = 1.287 g/cm3, F(000) = 432, 2θ range 2.50–26.37°; R indices (all data): R1 = 0.0630, wR2 = 0.1108
  • 15 Isabelle ME, Wightman RH, Avdovich HW, Laycock DE. Can. J. Chem. 1980; 58: 1344
    CrossrefSearch in Google Scholar
  • 17 Han X, Armstrong DW. Org. Lett. 2005; 7: 4205
    CrossrefSearch in Google Scholar