Rh(II)-Catalyzed Selective C(sp3)–H/C(sp2)–H Bonds Cascade Insertion to Construct [6–8–6] Benzo-Fused Scaffold

IF 4.9 1区 化学 Q1 CHEMISTRY, ORGANIC
Tao Yu, Feifei Fang, Haowen Shou, Yazhou Li, Zhiyan Qu, Feiyang Chen, Yu Zhang, Jiang Wang, Hong Liu
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引用次数: 0

Abstract

The fused eight-membered carbocycles (EMCs) play vital roles in the medicinal and biological investigations of many natural products and marketed drugs. The traditional synthesis of [6–8–6] benzo-fused derivatives involves multistep reactions and low yields, making the development of a one-step synthesis method a more challenging work. Here, we present a novel strategy for one-step construction of [6–8–6] benzo-fused scaffold from propargyl diazoacetates substituted with benzyl-nitrogen heterocyclic ring via Rh(ll)-catalyzed carbene/alkyne metathesis (CAM) and selective C–H bond insertion. This method exhibits a specific substrate scope, simple operation, mild reaction conditions, and high atom efficiency. Mechanistically, the process involves sequential CAM, 1,3-H-shift, intramolecular nucleophilic attack, and selective C(sp3)–H/C(sp2)–H bonds cascade insertion. Notably, the unique spirocyclic zwitterionic intermediate generated in this sequence contributes to N-heterocycle migration and fused eight-membered carbocycle formation. Additionally, the C(sp3)–H bond insertion connected to the oxygen atom rather than the nitrogen atom has been unexpectedly confirmed with the assistance of the spirocyclic zwitterionic intermediate. Overall, our findings open up a new avenue for the construction of [6–8–6] benzo-fused scaffold.

Abstract Image

Rh(II)催化选择性C(sp3) -H /C(sp2) -H键级联插入构建[6-8-6]苯并熔接支架
融合八元碳环(EMCs)在许多天然产物和上市药物的医学和生物学研究中发挥着重要作用。传统的[6-8-6]苯并衍生物的合成涉及多步反应和低收率,使得一步合成方法的开发更具挑战性。本研究提出了一种以苯氮杂环取代的丙炔重氮乙酸酯为原料,通过Rh(ll)催化的碳炔复合反应(CAM)和选择性的碳氢键插入,一步构建[6-8-6]苯并融合支架的新策略。该方法具有底物范围广、操作简单、反应条件温和、原子效率高等特点。从机理上讲,这一过程包括连续的CAM、1,3-H移位、分子内亲核攻击和选择性的C(sp3) -H /C(sp2) -H键级联插入。值得注意的是,在这个序列中产生的独特的螺环两性离子中间体有助于n -杂环的迁移和融合八元碳环的形成。此外,在螺环两性离子中间体的帮助下,C(sp3) -H键插入连接到氧原子而不是氮原子,这一发现出乎意料地得到了证实。总之,我们的研究结果为[6-8-6]苯融合支架的构建开辟了一条新的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Organic Letters
Organic Letters 化学-有机化学
CiteScore
9.30
自引率
11.50%
发文量
1607
审稿时长
1.5 months
期刊介绍: Organic Letters invites original reports of fundamental research in all branches of the theory and practice of organic, physical organic, organometallic,medicinal, and bioorganic chemistry. Organic Letters provides rapid disclosure of the key elements of significant studies that are of interest to a large portion of the organic community. In selecting manuscripts for publication, the Editors place emphasis on the originality, quality and wide interest of the work. Authors should provide enough background information to place the new disclosure in context and to justify the rapid publication format. Back-to-back Letters will be considered. Full details should be reserved for an Article, which should appear in due course.
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