Synlett 2011(5): 722-724  
DOI: 10.1055/s-0030-1259677
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthetic Studies toward the Total Synthesis of Chlorahololide A

Shan Qian, Gang Zhao*
Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Rd., Shanghai 200032, P. R. of China
Fax: +86(21)64166128; e-Mail: zhaog@mail.sioc.ac.cn;
Further Information

Publication History

Received 25 December 2010
Publication Date:
22 February 2011 (online)

Abstract

The highly stereoselective synthesis of core framework 4, a pivotal intermediate for the total synthesis of chlorahololide A, is reported. The approach features t-BuCu-mediated stereoselective reduction of α,β-unsaturated diketone 8, Wharton transposition, Simmons-Smith cyclopropanation and cascade enol lactonization.

    References and Notes

  • 1 Yang SP. Gao ZB. Wang FD. Liao SG. Chen HD. Zhang CR. Hu GY. Yue JM. Org. Lett.  2007,  9:  903 
  • 2 Liu Y. Nan FJ. Tetrahedron Lett.  2010,  51:  1374 
  • 3a Deng LS. Ma ZX. Zhang YZ. Zhao G. Synlett  2007,  87 
  • 3b Deng LS. Ma ZX. Zhao G. Synlett  2008,  728 
  • 3c Ye ZQ. Deng LS. Qian S. Zhao G. Synlett  2009,  2469 
  • 3d Wu H. Zhang HL. Zhao G. Tetrahedron  2007,  63:  6454 
  • 4 Kwabata J. Fukushi Y. Tahara S. Mizutani J. Phytochemistry  1990,  29:  2332 
  • 5a Micheli RA. Hajos ZG. Cohen N. Parrish DR. Portland LA. Sciamanna W. Scott MA. Wehrli PA. J. Org. Chem.  1975,  40:  675 
  • 5b Isaacs RCA. Grandi MJD. Danishefsky SJ. J. Org. Chem.  1993,  58:  3938 ; and references therein
  • 6a Corey EJ. Huang AX. J. Am. Chem. Soc.  1999,  121:  710 
  • 6b Daniewski AR. Kiegiel J. J. Org. Chem.  1988,  53:  5534 
  • 7 Hwu JR. Wetzel JM. J. Org. Chem.  1985,  50:  3946 
  • 8 Ito Y. Hirao T. Saegusa T. J. Org. Chem.  1978,  43:  1011 
  • 9 Yadav VK. Kapoor KK. Tetrahedron  1995,  51:  8573 
  • 10a Hoveyda AH. Evans DA. Fu GC. Chem. Rev.  1993,  93:  1307 
  • 10b Lebel H. Marcoux JF. Molinaro C. Charette AB. Chem. Rev.  2003,  103:  977 
  • 11 Wharton PS. Bohlen DH. J. Org. Chem.  1961,  26:  3615 
  • 12 Grandi MJD. Coburn CA. Isaacs RCA. Danishefsky SJ. J. Org. Chem.  1993,  58:  7728 
  • 13 Charette AB. Lebel H. J. Org. Chem.  1995,  60:  2966 
  • 16 Thompson CF. Jamison TF. Jacobsen EN. J. Am. Chem. Soc.  2000,  122:  10482 
  • 17a Nair V. Sinhababu A. J. Org. Chem.  1978,  43:  5013 
  • 17b Caglioti L. Tetrahedron  1966,  22:  487 
  • 18 Dess DB. Martin JC. J. Org. Chem.  1983,  48:  4155 
  • 19 Tatsuta K. Shohei Y. Kurihara K. Tanabe K. Shinei R. Okonogi T. Tetrahedron Lett.  1997,  38:  1439 
14

The same operative procedure should be conducted to ensure that the starting material is completely consumed. For details, see the Supporting Information.

15

See the Supporting Information for details. CCDC 804060 (4) and 804061 (14) contain the supplementary crystallogra-phic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

20

Data of the Core Fragment 4
[α]D ²8 56.2 (c 0.12, CHCl3); mp 133-135 ˚C. IR (film): 2921, 2850, 1735, 1464, 1374, 1265, 1045 cm. ¹H NMR (400 MHz, CDCl3): δ = 6.16 (s, 1 H), 4.39 (t, J = 5.2 Hz, 1 H), 2.60-2.40 (m, 2 H), 2.20-2.10 (m, 1 H), 1.89 (s, 3 H), 1.80-1.65 (m, 1 H), 1.65-1.50 (m, 1 H), 1.30-1.20 (m, 1 H), 1.09 (s, 3 H), 0.91 (s, 9 H), 1.80-1.65 (m, 1 H), 0.10 (s, 3 H), 0.07 (s, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 171.2, 149.4, 149.3, 122.1, 121.0, 72.9, 61.9, 42.1, 29.1, 26.2, 25.8, 23.3, 21.4, 18.2, 12.1, 8.5, -4.7, -5.3. ESI-MS: m/z = 369.2 [M + Na]+. ESI-HRMS: m/z calcd for C20H30O3SiNa+ [M + Na]+: 369.1862; found: 369.1856.