General Synthesis of N-Alkylindoles from N,N-Dialkylanilines via [4 + 1] Annulative Double C-H Functionalization.
General Synthesis of N-Alkylindoles from N,N-Dialkylanilines via [4 + 1] Annulative Double C-H Functionalization.
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DOI：
10.1021/jacs.3c10751
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发表时间：
2023-11
影响因子：
15
通讯作者：
Bowen Zhang;Frederik R Erb;A. Vasilopoulos;E. Voight;E. Alexanian
中科院分区：
文献类型：
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作者：
Bowen Zhang;Frederik R Erb;A. Vasilopoulos;E. Voight;E. Alexanian
在合成和药物化学中，从简单的结构单元合成吲哚和新型多环杂环化合物的策略使合成成为流水线。在此，我们报告了一种通过容易获得的N，N-二烷基苯胺的双位点选择性C（sp3）-H/C（sp2）-H [4 + 1]成环来进行N-烷基吲哚的C-H官能化方法。该协议的特点是通过调谐的N-tBu酰胺基自由基和添加磺酰基重氮偶联伴侣的位点选择性氢原子转移，这促进了（杂）芳族核心的高度位点选择性均裂芳族取代。成环产物的温和脱羧使得能够将碳炔等同物整体引入到N，N-二烷基苯胺支架中。此外，吲哚化的位点选择性和温和条件有利于在后期功能化（LSF）设置中直接接近N-烷基吲哚支架。
Strategies enabling the construction of indoles and novel polycyclic heterocycles from simple building blocks streamline syntheses in synthetic and medicinal chemistry. Herein, we report a C-H functionalization approach to N-alkylindoles proceeding via a double, site-selective C(sp3)-H/C(sp2)-H [4 + 1] annulation of readily accessed N,N-dialkylanilines. This protocol features a site-selective hydrogen atom transfer by a tuned N-tBu amidyl radical and addition of a sulfonyl diazo coupling partner, which promotes highly site-selective homolytic aromatic substitution of the (hetero)aromatic core. Mild decarboxylation of the annulation product enables the overall introduction of a carbyne equivalent into the N,N-dialkylaniline scaffold. Furthermore, the site-selectivity and mild conditions of the indolization facilitate direct access to N-alkyl indole scaffolds in late-stage functionalization (LSF) settings.