Total syntheses of amphidinolides T1 and T4 via catalytic, stereoselective, reductive macrocyclizations
Total syntheses of amphidinolides T1 and T4 via catalytic, stereoselective, reductive macrocyclizations
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DOI：
10.1021/ja042733f
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发表时间：
2005-03-30
影响因子：
15
通讯作者：
Jamison, TF
中科院分区：
文献类型：
--
作者：
Colby, EA;O'Brien, KC;Jamison, TF
这项工作描述了使用两个镍催化的炔烃还原偶联反应全合成两栖类内酯 T1 和 T4，一种情况是与环氧化物（分子间）反应，另一种情况是与醛（分子内）反应。后者用于实现大环化，形成 C-C 键，并在两种天然产物合成中安装选择性 > 10:1 的立体中心。研究并讨论了分子间炔醛还原偶联反应用于连接关键片段的替代方法；结果发现，大环化（即分子内炔-醛偶联）在几个方面（非对映选择性、产率和合成长度）都更优越。炔烃-环氧化物还原偶联在构建相当于两种天然产物分子的大约一半的关键片段方面发挥了重要作用。在一种情况下（T4系列），炔烃-环氧化物偶联在二炔偶联中表现出非常高的位点选择性。还提出了在大环化中观察到的立体选择性模型。
Described in this work are total syntheses of amphidinolides T1 and T4 using two nickel-catalyzed reductive coupling reactions of alkynes, with an epoxide in one case (intermolecular) and with an aldehyde in another (intramolecular). The latter was used to effect a macrocyclization, form a C-C bond, and install a stereogenic center with > 10:1 selectivity in both natural product syntheses. Alternative approaches in which intermolecular alkyne-aldehyde reductive coupling reactions would serve to join key fragments were investigated and are also discussed; it was found that macrocyclization (i.e. intramolecular alkyne-aldehyde coupling) was superior in several respects (diastereoselectivity, yield, and length of syntheses). Alkyne-epoxide reductive couplings were instrumental in the construction of key fragments corresponding to approximately half of the molecule of both natural products. In one case (T4 series), the alkyne-epoxide coupling exhibited very high site selectivity in a coupling of a diyne. A model for the stereoselectivity observed in the macrocyclizations is also proposed.