全氟烷基卤化物作为含氟砌块在构建氟烷基取代杂环化合物中的研究进展

Perfluoroalkyl Halides as Fluorine-Containing Building Blocks for the Synthesis of Fluoroalkylated Heterocycles

有机氟化学和杂环化学的研究对药物研发、新材料制备等方面具有重要意义.过去几年中,利用高度商业化、低毒性、廉价、稳定、易操作的全氟烷基卤化物为含氟砌块构建氟烷基取代杂环化合物取得了重要进展.本综述将全氟烷基卤化物作为含氟砌块参与构建杂环化合物的报道进行总结:(1)通过全氟烷基卤化物的单个碳卤键官能化构建杂环化合物;(2)通过全氟烷基卤化物的多个碳卤键官能化构建杂环化合物.通过全氟烷基卤化物产生全氟烷基自由基(⋅Rf)继而对不饱和类型底物进行加成-环化串联,将含氟基团引入杂环,合成了一系列氟烷基取代杂环化合物,如喹氧啉、菲蒽、肼、噻唑、嘧啶、偶氮三环、异噁唑等.本文旨在为从事有机杂环合成和有机氟化学的研究人员提供参考和启示,从而有助于新的含氟砌块和新的氟化反应的设计开发.

The unique chemical and physical advantages conferred by incorporation of F-atoms/perfluoroalkyl groups(Rf)into organic compounds have gained widespread recognition throughout drug discovery,crop protection,polymer chemistry,and materials science.The past decades have witnessed a boom in organofluorine chemistry and heterocyclic chemistry mainly owing to the importance of fluorine-containing heterocycles.As a result,the exploitation of readily available fluorinated building blocks to attach Rf groups to various heterocycles has become an important topic in synthetic chemistry.On the other hand,perfluoroalkyl halide,as a low-toxic and environmentally friendly perfluoroalkyl building block,has been extensively utilized as a unique reagent in the heterocycle construction.Considering the great influence and synthetic potential of these novel avenues,we summarize the recent advances for the synthesis of fluoroalkylated heterocycles by using perfluoroalkyl halides as key fluorine-containing building blocks.One or three C—X bonds of perfluoroalkyl halides are cleaved/functionalized during the perfluoroalkylation and cyclization process,and a series of perfluoroalkylated heterocycles such as quinoxalines,phenanthridines,hydrazones,thiazoles,pyrimidines,aza-tricycles,isoxazoles,etc.were synthesized in moderate to good yields.With a specific emphasis on their proposed mechanism,we hope this review will be useful for medicinal and synthetic organic chemists who are interested in radical-mediated perfluoroalkylation.