Asymmetric Dearomative [4 + 2] Photocycloadditions of Quinolines with Alkenes Enabled by Organocatalytic Activation

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Authors: Junyu Zhou, Zichun Zhang, Minmin Zhu, Hesi Yang, Xinyi Cai, Xiaoming Feng, Haipeng Hu, Yangbin Liu
Cited by: 3
References: 69

Abstract

Dearomative photocycloaddition of planar arenes represents a powerful strategy for constructing three-dimensional molecular architectures and modulating the metabolic profiles of bioisosteres, with significant implications for medicinal chemistry. In particular, the catalytic asymmetric variants of these transformations offer efficient access to enantioenriched polycyclic and spirocyclic scaffolds. While impressive advances have been made with naphthalenes and indoles, the catalytic asymmetric dearomative photocycloaddition of bicyclic azaarenes─specifically quinolines─remains challenging because of the inherently low reactivity of aromatic systems and difficulties in controlling regio-, diastereo-, and enantioselectivity. In contrast to previous excited-state metal complexes, we herein report a cooperative catalytic system that integrates photoenergy transfer and chiral Brønsted acid catalysis to achieve asymmetric dearomatization of quinolines via a visible-light-driven [4 + 2] cycloaddition. This protocol employs a chiral N -triflyl-phosphoramide organocatalyst to regulate reactivity and selectivity simultaneously. A broad range of enantioenriched bridged polycyclic tetrahydroquinoline frameworks bearing multiple contiguous stereocenters are obtained in good yields with high regio-, diastereo-, and enantioselectivities (up to 89% yield, > 20:1 rr, > 20:1 dr, 95% ee). The synthetic utility is demonstrated through diverse product derivatizations, and a plausible reaction mechanism is proposed based on combined control experiments and DFT calculations.

Fields of Study & Subjects

Radical Photochemical Reactions Asymmetric Hydrogenation and Catalysis Catalytic C–H Functionalization Methods

Publication details

Journal / source
Journal of the American Chemical Society
Publisher
American Chemical Society (ACS)
Volume
148
Issue
24
Pages
25062–25074
Publication date
15 May 2026
Language
EN