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Synlett 2005(13): 2077-2079  
DOI: 10.1055/s-2005-871953
LETTER
© Georg Thieme Verlag Stuttgart · New York

Total Synthesis of (R)-(+)-Kavain via (MeCN)2PdCl2-Catalyzed Isomerization of a cis Double Bond and Sonochemical Blaise Reaction

Fang-Dao Wang, Jian-Min Yue*
State Key Laboratory of Drug Research, Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zuchongzhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, P. R. China
Fax: +86(21)50806718; e-Mail: jmyue@mail.shcnc.ac.cn;
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Publication History

Received 2 May 2005
Publication Date:
12 July 2005 (online)

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Abstract

From the chiral source 2,3-O-isopropylidene-d-glyceraldehyde 2, the natural product (R)-(+)-kavain 1a was efficiently synthesized in a total yield of 25% via (MeCN)2PdCl2-catalyzed isomerization of the cis double bond of an olefin as the key step and sonochemical Blaise reaction. The chiral center adjacent to the cis double bond was retained without protection of the free allylic hydroxy during the isomerization process.

Key words

kavain - total synthesis - (MeCN)2PdCl2-catalyzed - isomerization - cis double bond - sonochemical Blaise reaction

    References

  • 1 Sotheeswaran S. Chem. Aust.  1987,  377 
    Google Scholar
  • 2 He X.-G. Lin L.-Z. Lian L.-Z. Planta Med.  1997,  63:  70 
    Google Scholar
  • 3a Gleitz J. Friese J. Beile A. Ameri A. Peters T. Eur. J. Pharmacol.  1996,  315:  89 
    Google Scholar
  • 3b Seitz U. Ameri A. Pelzer H. Gleitz J. Peters T. Planta Med.  1997,  63:  303 
    Google Scholar
  • 3c Capasso A. Calignano A. Acta Ther.  1988,  14:  249 
    Google Scholar
  • 4 Gleitz J. Beile A. Wilkens P. Ameri A. Peters T. Planta Med.  1997,  63:  27 
    Google Scholar
  • 5a Kostermans D. Nature (London)  1950,  166:  788 
    CrossrefGoogle Scholar
  • 5b Fowler EMF. Henbest HB. J. Chem. Soc.  1950,  3642 
    CrossrefGoogle Scholar
  • 5c Klohs MW. Keller F. Williams RE. J. Org. Chem.  1959,  24:  1829 
    CrossrefGoogle Scholar
  • 5d Izawa T. Mukaiyama T. Chem. Lett.  1975,  161 
    CrossrefGoogle Scholar
  • 5e Israili ZH. Smissman EE. J. Org. Chem.  1976,  41:  4070 
    CrossrefGoogle Scholar
  • 5f Dziadulewicz E. Giles M. Moss WO. Gallagher T. Harman M. Hursthouse MB. J. Chem. Soc., Perkin Trans. 1  1989,  1793 
    CrossrefGoogle Scholar
  • 5g Spino C. Mayes N. Desfossés H. Sotheeswaran S. Tetrahedron Lett.  1996,  37:  6503 
    CrossrefGoogle Scholar
  • 5h Pierres C. George P. Hijfte LV. Ducep J.-B. Hibert M. Mann A. Tetrahedron Lett.  2003,  44:  3645 
    CrossrefGoogle Scholar
  • 6 Smith TE. Djang M. Velander AJ. Downey CW. Carroll KA. Alphen SV. Org. Lett.  2004,  6:  2317 
    CrossrefGoogle Scholar
  • 7 Blaise EE. C. R. Hebd. Seances Acad. Sci.  1901,  132 478. 
    Google Scholar
  • 8 Schmid CR. Bryant JD. Dowlatzedah M. Phillips JL. Prather DE. Schantz RD. Sear NL. Vianco CS. J. Org. Chem.  1991,  56:  4056 
    CrossrefGoogle Scholar
  • 9 Annunziata R. Cinquini M. Cozzi F. Gennari C. Raimondi L. J. Org. Chem.  1987,  52:  4674 
    CrossrefGoogle Scholar
  • 10 For a review see: Sonnet PE. Tetrahedron  1980,  36:  557 
    CrossrefGoogle Scholar
  • 11 Yu JQ. Gaunt MJ. Spencer JB. J. Org. Chem.  2002,  67:  4627 
    CrossrefPubMedGoogle Scholar
  • 13a Lee AS.-Y. Cheng R.-Y. Pan O.-G. Tetrahedron Lett.  1997,  38:  443 
    Article in Thieme ConnectGoogle Scholar
  • 13b Narkunan K. Uang B.-J. Synthesis  1998,  1713 
    Article in Thieme ConnectGoogle Scholar
  • 15 Soriente A. Rosa MD. Stanzione M. Villano R. Scettri A. Tetrahedron: Asymmetry  2001,  12:  959 
    CrossrefGoogle Scholar
  • 16 (R)-(+)-Kavain 1a: white crystals; mp 115-116 °C (lit.18 105-106 °C); [α]D 20 +110.2 (c 1.1, EtOH), {lit.18 [α]D 20 +105 (c 1, EtOH)}. IR (KBr): 1704.8, 1623.8, 1392.4, 1247.7, 1230.4 cm-1. 1H NMR (400 MHz, CDCl3): δ = 2.58-2.53 (dd, J = 4.4, 16.9 Hz), 2.71-2.64 (dd, J = 10.7, 16.9 Hz), 3.77 (s, 3 H), 5.07 (m, 1 H), 5.20 (s, 1 H), 6.29-6.24 (dd, J = 6.2, 16.1 Hz), 6.76 (d, J = 16.1 Hz), 7.41-7.26 (m, 5 H). EI-MS: m/z = 230 (M+). Anal. Calcd for C14H14O3: C, 73.03; H, 6.13. Found: C, 73.33; H, 6.12.
  • 17 Dharmaratne HRW. Nanayakkara NPD. Khan IA. Phytochemistry  2002,  59:  429 
    CrossrefGoogle Scholar
  • 18 Borsche W. Peitzsch W. Ber. Dtsch. Chem. Ges. B.  1930,  63:  2414 
    Google Scholar
12

Isomerization of the cis double bond: A solution of nitriles 5 (145 mg, 0.84 mmol) and bis(acetonitrile)palladium(II) chlorine (17.5 mg, 0.07 mmol) in benzene (5 mL) was stirred at reflux for ca. 5 h until the cis form of 5 was fully consumed (monitored by TLC). After removal of the solvent in vacuo, the residue was dissolved in EtOAc (50 mL) and filtered to remove the insoluble solid. The EtOAc soluble fraction was then purified by flash column chromatography on silica gel (EtOAc-petroleum ether, 1:4) to afford the desired pure trans form of 5 (132 mg, 91%) as a colorless oil. 1H NMR (400MHz, CDCl3): δ = 2.25 (br, 1 H), 2.63-2.69 (dd, J = 6.2, 16.7 Hz, 1 H), 2.69-2.75 (dd, J = 5.5, 16.7 Hz, 1 H), 4.652 (m, 1 H), 6.25 (dd, J = 6.7, 15.9 Hz, 1 H), 6.74 (d, J = 15.9 Hz, 1 H), 7.27-7.40 (m, 5 H); EI-MS: m/z =173 (M+).

14

Sonochemical reactions: A mixture of the trans form of 5 (205 mg, 1.18 mmol) and activated Zn (0.80 g, 12.3 mmol) in anhyd THF (10 mL) was subjected to ultrasonic irradiation at 50 °C for 10 min and then methyl bromoacetate (0.70 ml, 5.86 mmol) was added dropwise under a nitrogen atmosphere. The resultant mixture was irradiated under the same conditions for another 5 h, then acidified with 2 M HCl (to pH 3), stirred at r.t. for 10 min, and diluted with EtOAc (60 mL). The organic phase was washed with sat. NaHCO3 (20 mL), brine (20 mL), and then dried over anhyd Na2SO4. After evaporation of the solvent in vacuo, the residue was purified by column chromatography on silica gel (petroleum ether-EtOAc, 10:3) to afford the desired product 6 (206 mg, 70%), as a pale yellow oil. [α]D 20 +19.4 (c 1.15, CHCl3), {lit.15 [α]D 25 +20.2 (c 1.0, CHCl3)}. 1H NMR (400MHz, CDCl3): δ = 2.88 (d, J = 6.1 Hz, 2 H), 3.53 (s, 2 H), 3.75 (s, 3 H), 4.79 (m, 1 H), 6.22 (dd, J = 6.2, 15.9 Hz, 1 H), 6.67 (dd, J = 1.1, 15.9 Hz, 1 H), 7.25-7.39 (m, 5 H). EIMS: m/z = 248 (M+).