单/二/多氟烷基醚的合成研究进展

Advances in the Synthesis of Mono/Di/Polyfluoroalkyl Ethers

含氟烷基醚广泛应用于有机化学、材料科学、环境科学和生命科学等领域,尤其在生物医药领域,引入氟烷氧基能提高代谢稳定性、改善细胞膜通透性,从而明显改善生物活性分子的药效学和药代动力学特性而备受关注.尽管已经报道了多种构建含氟烷基醚的策略,市场上含氟烷基醚类药物和农用化学品的数量仍然很少,因此,开发制备含氟烷基醚类化合物的有效方法是一项需求很大且挑战性较强的工作.主要从C—O键偶联间接氟烷氧基化、C(sp^(2))—H、C(sp^(2))—C、C(sp^(3))—X(杂原子)直接氟烷氧基化和其它直接氟烷氧基化方面,分类总结了合成单氟甲基醚、二氟甲基醚和多氟烷基醚的研究进展,并探讨了部分反应可能的机理和适用范围.

Fluoroalkyl ethers are widely used in organic chemistry,materials science,environmental science,life science and other fields,especially in biopharmaceuticals,where the introduction of fluoroalkoxy groups has attracted much attention for their ability to improve metabolic stability and cell membrane permeability,thus significantly improving the pharmacodynamic and pharmacokinetic properties of biologically active molecules.Although several strategies for the construction of fluoroalkyl ethers have been reported,the number of fluoroalkyl ether-containing drugs and agrochemicals on the market is still small.Therefore,the development of effective methods for the preparation of fluoroalkyl ethers is a much needed and challenging task.The progress of research on the synthesis of monofluoromethyl ethers,difluoromethyl ethers,and polyfluoroalkyl ethers is categorized and summarized,mainly in terms of C—O bond-coupled indirect fluoroalkoxylation,C(sp^(2))—H,C(sp^(2))—C,C(sp^(3))—X(heteroatom)direct fluoroalkoxylation and other direct fluoroalkoxylation.The possible mechanisms and applica-bility of some reactions are also discussed.