Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (+)-Discodermolide. Part 4: Preparation of Fragment C7-24

Stuart J. Mickel, Gottfried H. Sedelmeier, Daniel Niederer, Friedrich Schuerch, Manuela Seger, Klaus Schreiner, Robert Daeffler, Adnan Osmani, Dominique Bixel, Olivier Loiseleur, Jacques Cercus, Hans Stettler, Karl Schaer, Remo Gamboni, Andrew Bach, Guang-Pei Chen, Weichun Chen, Peng Geng, George T. Lee, Eric LoeserJoesph McKenna, Frederick R. Kinder Jr, Kurt Konigsberger, Kapa Prasad, Timothy M. Ramsey, Noela Reel, Oljan Repic, Larry Rogers, Wen-Chung Shieh, Run-Ming Wang, Llladar Waykole, Song Xue, Gordon John Florence, Ian Paterson

Research output: Contribution to journalArticlepeer-review

89 Citations (Scopus)

Abstract

Coupling Of C9-14 (4) and C15-21 (5a) fragments to produce the cis-trisubstituted olefin was achieved using Suzuki-type coupling conditions employed by Marshall (5a/tert-BuLi/B-OMe-9-BBN added to 4/Cs2CO3/Pd(dPPf)(2)). The terminal (Z)-diene moiety was attached to aldehyde 10 by using a sequential Nozaki-Hiyama allylation and Peterson olefination sequence; careful monitoring of the disappearance of both diastereomeric beta-hydroxysilanes was found to be essential for achieving a high yield. In the oxidation of alcohols 12 and 16 to 13 and 7, respectively, using iodobenzene diacetate and TEMPO, addition of a trace of water was found to be crucial for complete conversion. The C8-9 (Z)-olefin functionality was introduced on to aldehyde 13 using a Still-Gennari HWE reaction. Subsequent carbamate installation at C-19 followed by a reduction/oxidation sequence gave the title fragment C7-24 (7) ready to be coupled with the C1-6 fragment, which is described in Part 2 of this series.

Original languageEnglish
Pages (from-to)113-121
Number of pages9
JournalOrganic Process Research & Development
Volume8
Issue number1
DOIs
Publication statusPublished - Jan 2004

Keywords

  • STEREOSELECTIVE SYNTHESIS
  • KETONES

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