Innate and guided C-H functionalization logic.
Innate and guided C-H functionalization logic.
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固有的和引导的 C-H 功能化逻辑。
DOI：
10.1021/ar200194b
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发表时间：
2012-06-19
影响因子：
18.3
通讯作者：
Baran, Phil S.
中科院分区：
文献类型：
--
作者：
Brueckl, Tobias;Baxter, Ryan D.;Ishihara, Yoshihiro;Baran, Phil S.
有机物的燃烧或许是人类所利用的最古老且最常见的化学转化。在此过程中以牺牲C - H键为代价生成C - O键可被视为C - H官能化的最基本形式。这说明了“C - H官能化”这一术语的极其宽泛性，因为它可以描述实际上任何C - H键向C - X键（X为除H以外的任何元素）的转化。因此，区分我们所认为的C - H官能化逻辑的两个不同类别可能是有用的：“导向型”和“本征型”。顾名思义，导向型C - H官能化是由外部试剂或导向基团（共价结合或短暂结合）引导，以牺牲特定靶向的C - H键来引入新的官能团。相反，本征型C - H官能化可广义地定义为在没有其他导向力的情况下，仅基于自然反应活性模式将C - H键交换为新官能团的反应。
体现这种区别的两种底物是二氢葑醇和异烟酸。羟基化或芳基化的C - H官能化过程分别可以在每个分子的多个位置发生。本征型官能化导致的取代模式是由经历C - H断裂的底物的固有偏向（空间位阻或电子效应）所决定的，而导向型官能化导致的取代模式是由外部导向力控制的，例如金属络合或试剂的空间位阻。尽管在不完全符合单一类别的情况下，导向型和本征型C - H官能化之间的区别可能并不总是清晰的，但在分析反应活性模式和合成策略时，这是一个有用的概念。我们必须强调，尽管在导向型和本征型C - H官能化之间进行完全严格的区分可能不切实际，但我们仍然发现它在合成的规划阶段是一个有用的工具。
在这篇综述中，我们通过“导向型”和“本征型”的描述来追溯我们自己在合成中C - H官能化领域的研究。我们展示了利用本征反应活性如何有利于实现杂环和羰基化合物之间独特的键构建，从而实现快速且可规模化的全合成。导向型和本征型官能化被协同使用，以可控的方式创造了一整个萜烯家族。我们接着讨论了高含氮量复杂生物碱的合成，这需要发明一种独特的化学选择性本征型C - H官能化方案。这些发现促使我们开发了一系列本征型C - H官能化反应，用于构建对大多数有机化学家（药物化学家）有重要意义的C - C键。无论是导向型还是本征型，C - H官能化逻辑的策略性使用都能对合成效率产生显著的积极影响。
The combustion of organic matter is perhaps the oldest and most common chemical transformation utilized by mankind. The generation of a C–O bond at the expense of a C–H bond during this process may be considered the most basic form of C–H functionalization. This illustrates the extreme generality of the term ‘C–H functionalization,’ as it can describe the conversion of literally any C–H bond into a C–X bond (X being anything except H). Therefore, it may be of use to distinguish between what, in our view, are two distinct categories of C–H functionalization logic: ‘guided’ and ‘innate.’ Guided C–H functionalizations, as the name implies, are guided by external reagents or directing groups (covalently or fleetingly bound) to install new functional groups at the expense of specifically targeted C–H bonds. Conversely, innate C–H functionalizations may be broadly defined as reactions that exchange C–H bonds for new functional groups based solely on natural reactivity patterns in the absence of other directing forces. Two substrates that illustrate this distinction are dihydrojunenol and isonicotinic acid. The C–H functionalization processes of hydroxylation or arylation, respectively, can take place at multiple locations on each molecule. Innate functionalizations lead to substitution patterns that are dictated by the inherent bias (steric or electronic) of the substrate undergoing C–H cleavage, whereas guided functionalizations lead to substitution patterns that are controlled by external directing forces such as metal complexation or steric bias of the reagent. Although the distinction between guided and innate C–H functionalizations may not always be clear in cases that do not fit neatly into a single category, it is a useful convention to consider when analyzing reactivity patterns and strategies for synthesis. We must emphasize that although a completely rigorous distinction between guided and innate C–H functionalization may not be practical, we have nonetheless found it to be a useful tool at the planning stage of synthesis. In this Account, we trace our own studies in the area of C–H functionalization in synthesis through the lens of ‘guided’ and ‘innate’ descriptors. We show how harnessing innate reactivity can be beneficial for achieving unique bond constructions between heterocycles and carbonyl compounds, enabling rapid and scalable total syntheses. Guided and innate functionalizations were used synergistically to create an entire family of terpenes in a controlled fashion. We continue with a discussion of the synthesis of complex alkaloids with high nitrogen content, which required the invention of a uniquely chemoselective innate C–H functionalization protocol. These findings led us to develop a series of innate C–H functionalization reactions for forging C–C bonds of interest to the largest body of practicing organic chemists: medicinal chemists. Strategic use of C–H functionalization logic can have a dramatically positive effect on the efficiency of synthesis, whether guided or innate.
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影响因子：
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