Li Bo-Jie, Ruan Yu-Long, Zhu Lei, Zhou Jian, Yu Jin-Sheng
Hubei Engineering University, Xiaogan, China.
State Key Laboratory of Petroleum Molecular & Process Engineering, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development; School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, P. R. China.
Chem Commun (Camb). 2024 Oct 22;60(85):12302-12314. doi: 10.1039/d4cc03788j.
Chiral organofluorine compounds featuring a monofluoromethyl (CHF)-substituted stereocenter are often encountered in a number of drugs and bioactive molecules. Consequently, the development of catalytic asymmetric methods for the enantioselective construction of CHF-substituted stereocenters has made great progress over the past two decades, and a variety of enantioselective transformations have been accordingly established. According to the types of fluorinated reagents or substrates employed, these protocols can be divided into the following major categories: (i) enantioselective ring opening of epoxides or azetidinium salts by fluoride anions; (ii) asymmetric monofluoromethylation with 1-fluorobis(phenylsulfonyl)methane; (iii) asymmetric fluorocyclization of functionalized alkenes with Selectfluor; and (iv) asymmetric transformations involving α-CHF ketones, α-CHF alkenes, or other CHF-containing substrates. This feature article aims to summarize these recent advances and discusses the possible reaction mechanisms, advantages and limitations of each protocol and their applications. Synthetic opportunities still open for further development are illustrated as well. This review article will be an inspiration for researchers engaged in asymmetric catalysis, organofluorine chemistry, and medicinal chemistry.
具有单氟甲基（CHF）取代的立体中心的手性有机氟化合物经常出现在许多药物和生物活性分子中。因此，在过去二十年中，用于对映选择性构建CHF取代的立体中心的催化不对称方法取得了很大进展，并相应地建立了各种对映选择性转化方法。根据所使用的氟化试剂或底物的类型，这些方法可分为以下几大类：（i）氟阴离子对环氧化物或氮杂环丁烷盐进行对映选择性开环；（ii）用1-氟双（苯磺酰基）甲烷进行不对称单氟甲基化；（iii）用Selectfluor对官能化烯烃进行不对称氟环化；以及（iv）涉及α-CHF酮、α-CHF烯烃或其他含CHF底物的不对称转化。这篇专题文章旨在总结这些最新进展，并讨论每种方法可能的反应机理、优点和局限性及其应用。还展示了仍有待进一步开发的合成机会。这篇综述文章将为从事不对称催化、有机氟化学和药物化学的研究人员提供启发。
