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Synthesis of Fluorinated Pyrrolo[2,1-<i>a</i>]isoquinolines through Decarboxylative/Dehydrofluorinative [3 + 2] Cycloaddition Aromatization of Isoquinolinium <i>N</i>-Ylides with Difluoroenoxysilanes

Wenxue Xi, Yiheng Zhang, Haijian Wu, Jinshan Li, Yurong Wang, Jianguo Yang, Zhiming Wang, Weijun Yao

2023Organic Letters18 citationsDOI

Abstract

A decarboxylative/dehydrofluorinative formal [3 + 2] cycloaddition aromatization of isoquinolinium N -ylides with difluoroenoxysilanes has been developed. This methodology provides a facile and straightforward synthetic pathway to afford highly functionalized fluorinated pyrrolo[2,1- a ]isoquinolines in good to excellent yields under mild conditions. Moreover, gram-scale and synthetic derivatization experiments for the late-stage functionalization of drug molecules have also been demonstrated.

Topics & Concepts

AromatizationChemistryCycloadditionDerivatizationCombinatorial chemistryMoleculeSurface modificationOrganic chemistryCatalysisHigh-performance liquid chromatographyPhysical chemistryFluorine in Organic ChemistrySynthesis and Reactivity of HeterocyclesCyclopropane Reaction Mechanisms
Synthesis of Fluorinated Pyrrolo[2,1-<i>a</i>]isoquinolines through Decarboxylative/Dehydrofluorinative [3 + 2] Cycloaddition Aromatization of Isoquinolinium <i>N</i>-Ylides with Difluoroenoxysilanes | Litcius