Taming Azide Radicals for Catalytic C-H Azidation
Taming Azide Radicals for Catalytic C-H Azidation
复制标题
DOI：
10.1021/acscatal.5b02474
复制
发表时间：
2016-02-01
期刊：
影响因子：
12.9
通讯作者：
Groves, John T.
中科院分区：
文献类型：
--
作者：
Huang, Xiongyi;Groves, John T.
尽管含有C-N-3键的分子在有机合成、化学生物学和药物发现中具有重要意义，但直接将脂肪族C-H键转化为烷基叠氮化合物的反应在合成反应中明显缺乏。利用有机分子中普遍存在的C-H键和叠氮官能团的多样性，这种转化可以在不同的学科中有广泛的应用。自由基C-H活化是实现脂肪族C-H叠氮化的一种很有吸引力的策略，因为它克服了传统有机金属方法在激活惰性脂肪族C-H键方面的许多缺点。通过氢原子抽提的自由基C-H活化与合适的叠氮化物转移试剂相结合，可以实现新的C-H叠氮化方法。从这个角度，我们回顾了自由基碳氢叠氮化反应的历史，并总结了该领域的几个重要的最新进展。到目前为止，所有的自由基C-H叠氮化都遵循一个一般的方法，包括最初的自由基C-H提取步骤和随后的叠氮转移到初始的碳心自由基。这一观点的一个特别重点是在C-H叠氮化反应中使用过渡金属催化剂的有益效果，与以前的方法相比，这种催化剂“驯服”了叠氮自由基，导致了在温和得多的条件下有效进行的反应，并提供了更广泛的底物范围和更高的区域选择性和立体选择性。
Reactions that directly transform aliphatic C-H bonds into alkyl azides are noticeably lacking in the repertoire of synthetic reactions, despite the importance of molecules containing C-N-3 bonds in organic synthesis, chemical biology, and drug discovery. Harnessing the ubiquity of C-H bonds in organic molecules and the versatility of the azide functional group, such transformations could have broad applications in various disciplines. Radical C-H activation represents an appealing strategy to achieve aliphatic C-H azidation, as it overcomes many drawbacks of conventional organometallic approaches in activating inert aliphatic C-H bonds. Novel C-H azidation methodologies could be realized by combining radical C-H activation via hydrogen atom abstraction with suitable azide-transfer reagents. In this perspective, we survey the history of radical C-H azidation and summarize several significant recent advances in the field. All radical C-H azidations to date follow a general approach comprising an initial radical C-H abstraction step and a subsequent azide transfer to the incipient carbon-centered radicals. A particular focus of this perspective is on the beneficial effects of using transition-metal catalysts in C-H azidation reactions, which have "tamed" azide radicals and led to reactions that proceed efficiently under much milder conditions and provide broader substrate scope and higher regioselectivities and stereoselectivities, compared to previous approaches.