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Updated: Jun 25, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Electrophilic Fluorine-Mediated Povarov Cyclization: Access to Fluorinated Quinolines via in Situ Generated
Zhi-Chao Qi1, Zhi-Hao Xu1, Meng-Xiao Bi1
1College of Food Science and Pharmaceutical Engineering, Key Laboratory of National Forestry and Grassland Administration on Pomegranate, Zaozhuang University, Zaozhuang, Shandong Province 277160, China.
Abstract:
Electrophilic fluorine-mediated synthesis of mono- and difluorinated quinolines is developed via a Povarov-type cycloaddition. The reaction involves the in situ generation of highly reactive fluoroketenimine intermediates from readily accessible phosphorus ylides under metal-free and mild conditions. The electrophilic fluorinating reagent functions as both a fluorine source and an oxidant, enabling a one-pot, step-economic cascade process. This protocol exhibits broad functional group compatibility and delivers a wide array of fluorinated quinoline derivatives in good to excellent yields. Gram-scale preparation and late-stage modification of pharmaceutical scaffolds further validated the synthetic utility of this approach.
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