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

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 intermolecular 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.

Keywords

Dearomatization / Energy transfer / Excited state proton transfer / Indole / Spiroindoline

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