A simple and modular strategy for small molecule synthesis: Iterative Suzuki-Miyaura coupling of B-protected haloboronic acid building blocks
A simple and modular strategy for small molecule synthesis: Iterative Suzuki-Miyaura coupling of B-protected haloboronic acid building blocks
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DOI：
10.1021/ja0716204
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发表时间：
2007-05-30
影响因子：
15
通讯作者：
Burke, Martin D.
中科院分区：
文献类型：
--
作者：
Gillis, Eric P.;Burke, Martin D.
我们在此描述了一种用于小分子合成的简单且高度模块化的策略，该策略涉及B - 保护的双官能团卤代硼酸的迭代交叉偶联。为实现这一方法，我们新发现通过与三价配体N - 甲基亚氨基二乙酸络合使硼酸锥体化会抑制其对交叉偶联的反应性。这种配体在无水铃木 - 宫浦反应条件下非常稳定，但使用温和的碱水溶液（1 M氢氧化钠水溶液/四氢呋喃，10分钟，23℃或饱和碳酸氢钠水溶液/甲醇，23℃，6小时）可轻易裂解。尽管芳基、杂芳基、烯基和烷基硼酸的反应性可能有很大差异，但这种方法对于保护和解保护所有四类亲核试剂都是有效的。利用这一潜力，我们通过迭代使用铃木 - 宫浦反应，将一系列易于合成、易于纯化且高度稳定的结构单元组合在一起，首次完成了天然产物鼠李碱的全合成。
We herein describe a simple and highly modular strategy for small molecule synthesis involving the iterative cross-coupling of B-protected bifunctional haloboronic acids. Enabling this approach, we have newly discovered that the pyramidalization of boronic acids via complexation with the trivalent ligand N-methyliminodiacetic acid inhibits their reactivity towards cross-coupling. This ligand is remarkably stable to anhydrous Suzuki-Miyaura conditions yet readily cleaved using mild aqueous base (1 M aqueous NaOH/THF, 10 min, 23 degrees C or saturated aqueous NaHCO3/MeOH, 23 degrees C, 6 h). Although the reactivity of aryl, heteroaryl, alkenyl, and alkyl boronic acids can vary dramatically, this methodology is effective for protecting and deprotecting all four classes of nucleophiles. Harnessing this potential, we achieved the first total synthesis of the natural product ratanhine using the Suzuki-Miyaura reaction iteratively to bring together a collection of easily synthesized, readily purified, and highly robust building blocks.