In the past decade, single-atom skeletal editing, which involves the precise insertion, deletion, or exchange of single atoms in the core skeleton of a molecule, has emerged as a promising synthetic strategy for the rapid construction or diversification of complex molecules without laborious de novo synthetic processes. Among them, carbene-initiated skeletal editing is particularly appealing due to the ready availability and diverse reactivities of carbene species. The initial endeavors to modify the core skeleton of heteroarenes through carbon-atom insertion could date back to 1881, when Ciamician and Denstedt described the conversion of pyrroles to pyridines by trapping haloform-derived free carbene. Despite its potential synthetic value, the general applicability of this one-carbon insertion has seen limited progress due to poor yields and harsh reaction conditions. Significant advances in skeletal editing via carbene insertion were achieved only in the past 3 years by Levin, Ball, Xu, Song, Glorius, and others. The hallmark of these approaches is facile halocyclopropanation followed by regioselective ring opening facilitated by the expulsion of the halide ion. Consequently, only specially designed α-halocarbene precursors, such as haloform derivatives, α-halodiazoacetates, chlorodiazirines, and α-chlorodiazo oxime esters, can be employed to achieve Ciamician–Denstedt-type skeletal editing. This not only limits the types of functional groups installed on the ring expansion products but also prevents their widespread adoption, especially in late-stage contexts. The enduring quest to develop environmentally friendly and versatile carbene precursors, superior functional group compatibility, and potential application in late-stage diversifications and the investigation of mechanistic insights into carbon insertion reactions remain a fundamental objective.

中文翻译：

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Triftosylhydrazone 在单原子骨骼编辑中的应用


在过去的十年中，单原子骨架编辑，涉及在分子的核心骨架中精确插入、删除或交换单个原子，已成为一种很有前途的合成策略，用于快速构建或多样化复杂分子，而无需费力的从头合成过程。其中，卡宾引发的骨骼编辑特别有吸引力，因为卡宾种类的现成可用性和多种反应性。通过碳原子插入修饰杂芳烃核心骨架的最初努力可以追溯到 1881 年，当时 Ciamician 和 Denstedt 描述了通过捕获卤仿衍生的游离卡宾将吡咯转化为吡啶。尽管具有潜在的合成价值，但由于产率低和反应条件恶劣，这种单碳插入的普遍适用性进展有限。Levin、Ball、Xu、Song、Glorius 等人仅在过去 3 年中才在通过卡宾插入进行骨骼编辑方面取得了重大进展。这些方法的特点是简单的卤环丙烷化，然后通过卤化物离子的排出促进区域选择性开环。因此，只有专门设计的α-卤代卡宾前体，如卤仿衍生物、α-卤代氮唑乙酸酯、氯二氮嗪和 α-氯六氮肟酯，才能用于实现 Ciamician-Denstedt 型骨骼编辑。这不仅限制了扩环产品上安装的官能团类型，而且阻碍了它们的广泛采用，尤其是在后期环境中。 对开发环保和多功能卡宾前体、卓越的官能团相容性、在后期多样化中的潜在应用以及对碳插入反应的机理见解的研究的持久追求仍然是一个基本目标。