A Highly Selective Nucleophilic and Radical Relay Difluorination of Cyclopropanes and Alkenes

J Junheng Liu (State Key Laboratory of Coordination Chemistry Jiangsu Key Laboratory of Advanced Organic Materials Chemistry and Biomedicine Innovation Center (ChemBIC) School of Chemistry and Chemical Engineering Nanjing University Nanjing 210023 China) H Haonan Bai (State Key Laboratory of Coordination Chemistry Jiangsu Key Laboratory of Advanced Organic Materials Chemistry and Biomedicine Innovation Center (ChemBIC) School of Chemistry and Chemical Engineering Nanjing University Nanjing 210023 China) Z Zhehan Liang (State Key Laboratory of Coordination Chemistry Jiangsu Key Laboratory of Advanced Organic Materials Chemistry and Biomedicine Innovation Center (ChemBIC) School of Chemistry and Chemical Engineering Nanjing University Nanjing 210023 China) Y Yuxi Gao W Weipeng Li (State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing Drum Tower Hospital, Jiangsu Key Laboratory of Advanced Organic Materials, Chemistry and Biomedicine Innovation Center (ChemBIC)) L Li‐Qu Huang (Children's Hospital of Nanjing Medical University Nanjing 210008 China) T Tao Zhong (Institute of Fundamental and Frontier Sciences) G Guichao Dong (State Key Laboratory of Coordination Chemistry Jiangsu Key Laboratory of Advanced Organic Materials Chemistry and Biomedicine Innovation Center (ChemBIC) School of Chemistry and Chemical Engineering Nanjing University Nanjing 210023 China) C Chengjian Zhu (State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing Drum Tower Hospital, Jiangsu Key Laboratory of Advanced Organic Materials, Chemistry and Biomedicine Innovation Center (ChemBIC)) J Jin Xie

Abstract

Abstract Fluoro‐containing organic compounds have been found wide application in pharmaceutical and agrochemical industries and in medical diagnostics. In this field, the construction of C─F bonds through nucleophilic fluorination strategies remains highly challenging. Herein, we have developed a radical‐polar strategy for visible‐light‐induced nucleophilic fluorination and subsequent radical fluorination, allowing for direct difluorination of cyclopropanes and styrenes under mild reaction conditions. It affords a series of structurally diverse, both 1,3‐ and 1,2‐difluorinated products in synthetically useful yields by means of ∼0.1 mol% of 4CzIPN as catalyst. Furthermore, only 3 equivalents of Et 3 N·3HF are required to realize an efficient nucleophilic fluorination, while 1.7 equivalents of Selectfluor are used as the radical fluorinating source, demonstrating good functional group compatibility and thus can be applied in late‐stage difluorination of complex molecules.

Article Details

Volume / Issue Vol. 64, Issue 44
Published October 27, 2025
ISSN 1433-7851
Publisher Wiley

Journal Info

Angewandte Chemie International Edition

Wiley

ISSN: 1433-7851 Physical Sciences

Authors (10)

J

Junheng Liu

State Key Laboratory of Coordination Chemistry Jiangsu Key Laboratory of Advanced Organic Materials Chemistry and Biomedicine Innovation Center (ChemBIC) School of Chemistry and Chemical Engineering Nanjing University Nanjing 210023 China

H

Haonan Bai

State Key Laboratory of Coordination Chemistry Jiangsu Key Laboratory of Advanced Organic Materials Chemistry and Biomedicine Innovation Center (ChemBIC) School of Chemistry and Chemical Engineering Nanjing University Nanjing 210023 China

Z

Zhehan Liang

State Key Laboratory of Coordination Chemistry Jiangsu Key Laboratory of Advanced Organic Materials Chemistry and Biomedicine Innovation Center (ChemBIC) School of Chemistry and Chemical Engineering Nanjing University Nanjing 210023 China

Y

Yuxi Gao

W

Weipeng Li

State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing Drum Tower Hospital, Jiangsu Key Laboratory of Advanced Organic Materials, Chemistry and Biomedicine Innovation Center (ChemBIC)

L

Li‐Qu Huang

Children's Hospital of Nanjing Medical University Nanjing 210008 China

T

Tao Zhong

Institute of Fundamental and Frontier Sciences

G

Guichao Dong

State Key Laboratory of Coordination Chemistry Jiangsu Key Laboratory of Advanced Organic Materials Chemistry and Biomedicine Innovation Center (ChemBIC) School of Chemistry and Chemical Engineering Nanjing University Nanjing 210023 China

C

Chengjian Zhu

State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing Drum Tower Hospital, Jiangsu Key Laboratory of Advanced Organic Materials, Chemistry and Biomedicine Innovation Center (ChemBIC)

J

Jin Xie