Total Synthesis of Hamigerans and Analogues Thereof. Photochemical Generation and Diels−Alder Trapping of Hydroxy-o-quinodimethanes

K. C. Nicolaou,* David L. F. Gray, and Jinsung Tae
Contribution from the Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, and Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093
J. Am. Chem. Soc., 2004, 126 (2), pp 613–627
DOI: 10.1021/ja030498f
Publication Date (Web): December 17, 2003
Copyright © 2004 American Chemical Society
*

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

, kcn@scripps.edu

Abstract

Abstract Image

A number of naturally occurring substances, including hamigerans, contain ring systems which are fused to an aromatic nucleus. A general and streamlined method for the construction of such benzannulated bi- and polycyclic carbon frameworks has been developed, and its scope and limitations were explored. On the basis of the photoenolization of substituted benzaldehydes and subsequent Diels−Alder (PEDA) trapping of the generated hydroxy-o-quinodimethanes, this method was optimized to set the stage for the total synthesis of several naturally occurring members of the hamigeran class. Specifically, the developed synthetic technology served as the centerpiece process for the successful asymmetric synthesis of hamigerans A (2), B (3), and E (7). In addition to the PEDA reactions, several other novel reaction processes are described, including a high-yielding decarbonylative ring contraction and an oxidative decarboxylation of a hydroxyl β-keto ester to afford an α-diketone. A number of analogues of these biologically active natural products were also prepared by application of the developed technology.

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History

  • Published In Issue January 21, 2004
  • Received August 18, 2003

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