有机化学 上一篇    下一篇

综述与进展

脱硫氟化构建N-氟烷基化合物的研究进展

汪静莉a, 陈曦b, 马立业a, 易文斌*,a   

  1. a南京理工大学化学与化工学院 南京 210014;
    b南京理工大学新能源学院 江阴 214443
  • 收稿日期:2026-06-03 修回日期:2026-06-24
  • 基金资助:
    国家自然科学基金(No. 22108124)资助项目.

Research Progress on the Construction of N-Fluoroalkyl Compounds via Desulfurative Fluorination

Wang Jinglia, Chen Xib, Ma Liyea, Yi Wenbina,*   

  1. aSchool of Chemistry and Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210014;
    aSchool of New Energy, Nanjing University of Science and Technology, Jiangyin 214443
  • Received:2026-06-03 Revised:2026-06-24
  • Contact: *E-mail: yiwb@njust.edu.cn
  • Supported by:
    National Natural Science Foundation of China (No. 22108124).

N-氟烷基化合物是医药、农药及功能材料领域的重要功能分子,将氟烷基引入胺类氮原子可精准调控分子理化性质与生物活性,现已成为药物结构修饰的研究热点。脱硫氟化作为构建N-氟烷基结构的高效策略,以硫代酰胺、二硫代氨基甲酸酯、硫代氨基甲酰氟及硫代异氰酸酯等硫代羰基化合物为前体,在氟化试剂、路易斯酸或氧化助剂作用下实现C=S键脱硫转化,高效构筑N-CF3N-CF2H、N-CH2F及全氟烷基官能团。本文系统综述了近年来脱硫氟化法合成各类N-氟烷基化合物的研究进展,总结了不同硫代前体的反应规律、作用机理及底物适用范围,评述了各类合成策略的优势与局限性。同时介绍了该类化合物在抗菌活性分子、杂环药物及功能砌块合成中的应用,并分析了当前脱硫氟化技术存在的底物普适性不足、工业化工艺欠缺等问题。最后对新型催化体系、绿色氟化技术及规模化合成方法的发展方向进行了展望,旨在为含氟胺类功能分子的设计与合成提供参考。

关键词: 脱硫氟化, N-氟烷基化合物, 硫代羰基化合物, 三氟甲基化, 二氟甲基化

N-Fluoroalkyl compounds are important functional molecules in the fields of medicine, agrochemicals, and functional materials. The introduction of fluoroalkyl groups onto the nitrogen atom of amines can precisely modulate the physicochemical properties and biological activities of molecules, and has become a research hotspot in drug-structure modification. Desulfurative fluorination, as an efficient strategy for constructing N-fluoroalkyl structures, employs thiocarbonyl compounds such as thioamides, dithiocarbamates, thiocarbamoyl fluorides, and isothiocyanates as precursors. In the presence of fluorinating reagents, Lewis acids, or oxidizing additives, this strategy enables desulfurative transformation of C=S bonds, thereby efficiently constructing N-CF3, N-CF2H, N-CH2F, and perfluoroalkyl functional groups. This review systematically summarizes recent advances in the synthesis of diverse N-fluoroalkyl compounds via desulfurative fluorination, concludes the reaction rules, mechanisms and substrate scope of various thiocarbonyl precursors, and discusses the merits and limitations of different synthetic strategies. The advantages and limitations of various synthetic strategies are also discussed. In addition, the applications of these compounds in the synthesis of antibacterial molecules, heterocyclic drugs, and functional building blocks are introduced. Current challenges, including insufficient substrate generality and the lack of industrially scalable processes, are analyzed. Finally, future directions, such as the development of novel catalytic systems, green fluorination technologies, and scalable synthetic methods, are discussed, with the aim of providing guidance for the design and synthesis of functional fluorinated amine molecules.

Key words: Desulfurative fluorination, N-Fluoroalkyl compounds, Thiocarbonyl compounds, Trifluoromethylation, Difluoromethylation