西南医科大学付强研究小组揭示了具有酰胺官能团的吲哚衍生物的能量转移介导的三重态激发态质子转移脱芳化。相关论文于2025年2月24日发表在《中国化学》杂志上。

在这项研究中，课题组研究人员报道了一种可见光催化的带有酰胺基团的吲哚衍生物的分子内脱芳化，通过能量转移合成了螺旋吲哚啉。该方法能够以中高收率高效地生成一系列羟基取代螺啉，在轻度反应条件下具有优异的非对映选择性(>20:1)。对照实验证实了能量传递途径参与了反应机理。密度泛函理论（DFT）进一步揭示了吲哚核与吡啶环之间的π-π堆叠相互作用，以及激发态下吡啶氮与六氟异丙醇（HFIP）之间氢键的增强。这些相互作用促进了能量转移介导的三态激发态分子内质子转移（T-ESPT），这对于激活其他酰胺功能至关重要。该成果代表了利用酰胺基团的反应性进行脱芳转化的罕见例子。

据介绍，具有酰胺官能团的吲哚衍生物的去芳构化提出了一个重大挑战，因为酰胺羰基的固有稳定性是由氮孤对离域引起的，从而增加了共振稳定性。

附：英文原文

Title: Energy Transfer-Mediated, Triplet Excited State Proton Transfer-Enabled Dearomatization of Indole Derivatives with Amide Functionalities

Author: Li Yang, Yi Pan, Peng Zhang, Liping Shi, Sheng Huang, Yijing Shu, Zhijie Zhang, Yimou Gong, Li Wang, Kai-Chung Lau, Qiang Fu

Issue&Volume: 2025-02-24

Abstract: The dearomatization of indole derivatives bearing amide functionalities presents a significant challenge due to the inherent stability of the amide carbonyl group, resulting from nitrogen lone-pair delocalization that imparts increased resonance stabilization. In this study, we report a visible-light photocatalytic intramolecular dearomatization of indole derivatives with amide groups, achieving the synthesis of spiroindolines via energy transfer. This method enables the efficient formation of a range of hydroxyl-substituted spiroindolines in moderate to high yields, with excellent diastereoselectivity (>20 : 1) under mild reaction conditions. Control experiments confirmed the involvement of an energy transfer pathway in the reaction mechanism. Density Functional Theory (DFT) calculations further revealed π-π stacking interactions between the indole core and pyridine ring, along with the strengthening of hydrogen bonding between the pyridine nitrogen and hexafluoroisopropanol (HFIP) in the excited state. These interactions facilitated the energy transfer-mediated triplet excited state intramolecular proton transfer (T-ESPT), crucial for activating the otherwise amide functionality. This protocol represents a rare example of harnessing the reactivity of amide groups for dearomative transformations.

DOI: 10.1002/cjoc.202401146

Source: https://onlinelibrary.wiley.com/doi/full/10.1002/cjoc.202401146