Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (+)-Discodermolide. Part 4: Preparation of Fragment C7-24
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- 作者：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
- 刊名：Organic Process Research & Development
- 出版年：2004
- 出版时间：January 2004
- 年：2004
- 卷：8
- 期：1
- 页码：113 - 121
- 全文大小：161K
- 年卷期：v.8,no.1(January 2004)
- ISSN：1520-586X
文摘
Coupling of C9-14 (4) and C15-21 (5a) fragments to produce thecis-trisubstituted olefin was achieved using Suzuki-type couplingconditions employed by Marshall (5a/tert-BuLi/B-OMe-9-BBNadded to 4/Cs2CO3/Pd(dppf)2). The terminal (Z)-diene moietywas attached to aldehyde 10 by using a sequential Nozaki-Hiyama allylation and Peterson olefination sequence; carefulmonitoring of the disappearance of both diastereomeric 
-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 traceof water was found to be crucial for complete conversion. TheC8-9 (Z)-olefin functionality was introduced on to aldehyde 13using a Still-Gennari HWE reaction. Subsequent carbamateinstallation at C-19 followed by a reduction/oxidation sequencegave the title fragment C7-24 (7) ready to be coupled with theC1-6 fragment, which is described in Part 2 of this series.
-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 traceof water was found to be crucial for complete conversion. TheC8-9 (Z)-olefin functionality was introduced on to aldehyde 13using a Still-Gennari HWE reaction. Subsequent carbamateinstallation at C-19 followed by a reduction/oxidation sequencegave the title fragment C7-24 (7) ready to be coupled with theC1-6 fragment, which is described in Part 2 of this series.