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Enantioselective Dearomative [2π + 2σ] Photocycloaddition of Naphthalene Derivatives with Bicyclo[1.1.0]butanes Enabled by Gd(III) Catalysis

Wenjie Shen, Xin-Xuan Zou, Muzi Li, Yuan‐Zheng Cheng, Shu‐Li You

2025Journal of the American Chemical Society52 citationsDOI

Abstract

The cycloaddition reactions of bicyclo[1.1.0]butanes with alkenes, imines, nitrones, or aziridines have served as an efficient platform to create conformationally restricted saturated bicyclic scaffolds. However, the use of readily available aromatics in such reactions, especially in an asymmetric manner, remains underexplored. Herein, we report a highly regio- and enantioselective dearomative [2π + 2σ] photocycloaddition reaction between naphthalene derivatives and bicyclo[1.1.0]butanes, enabled by Gd(III) catalysis. Bicyclo[1.1.0]butanes and naphthalenes adorned with a diverse array of functional groups are well-tolerated under mild conditions, affording enantioenriched pharmaceutically important bicyclo[2.1.1]hexanes in 30-96% yields with 81-93% ee and 12:1 → >20:1 rr. The synthetic versatility of this reaction is further demonstrated by the facile removal of directing group and derivatizations of the dearomatized product. UV-vis absorption spectroscopy studies suggest the involvement of an excited naphthalene species in the reaction process.

Topics & Concepts

ChemistryBicyclic moleculeNaphthaleneEnantioselective synthesisCatalysisCombinatorial chemistryMedicinal chemistryOrganic chemistryStereochemistryRadical Photochemical ReactionsCyclopropane Reaction MechanismsOxidative Organic Chemistry Reactions
Enantioselective Dearomative [2π + 2σ] Photocycloaddition of Naphthalene Derivatives with Bicyclo[1.1.0]butanes Enabled by Gd(III) Catalysis | Litcius