Acta Chimica Sinica ›› 2023, Vol. 81 ›› Issue (5): 520-532.DOI: 10.6023/A23030088 Previous Articles     Next Articles

Review

二氟环丙烯参与的有机反应研究进展

黄家翩a, 刘飞a, 吴劼*,a,b()   

  1. a 台州学院 医药化工学院&高等研究院 台州 318000
    b 中国科学院上海有机化学研究所 金属有机化学国家重点实验室 上海 200032
  • 投稿日期:2023-03-21 发布日期:2023-04-20
  • 作者简介:

    黄家翩, 台州学院高等研究院实验员, 在读博士. 主要从事有机合成方法学研究. 2017年6月获得江西师范大学有机化学专业硕士学位, 随后加入中国科学院上海有机化学研究所游书力研究员课题组从事研究助理工作. 2019年8月进入台州学院工作. 至今为止, 在Nat. Commun.; ACS Catal.; Org. Lett.; Org. Chem. Front.等期刊发表SCI论文近20篇, 获得中国发明专利4项.

    刘飞, 2020年6月获得南昌师范学院学士学位, 随后考入江西师范大学攻读硕士学位. 2021年7月加入台州学院吴劼教授课题组(联合培养研究生).

    吴劼, 教授、博士生导师. 2000年毕业于中国科学院上海有机化学研究所获得博士学位, 2000至2004年先后在美国哈佛大学(博士后)、洛克菲勒大学艾伦·戴蒙德艾滋病研究中心(访问科学家)及VivoQuest, Inc.(研究员)从事有机合成、药物化学及相关研究工作, 2004年9月回国加入复旦大学化学系(副教授), 2006年4月晋升为教授. 2019年9月加入台州学院. 目前主要研究领域为药物结构导向的有机合成方法学研究. 独立工作以来已在Nat. Commun.; J. Am. Chem. Soc.; Angew. Chem. Int. Ed.; Chem. Soc. Rev.等国际核心期刊发表SCI论文360余篇(其中IF>5.0论文220余篇), 论文被引用18500余次, 参与编写专著四本, 独立撰写专著一本, 获得美国发明专利2项, 中国发明专利32项. 先后担任“ACS Combinatorial Science”,“化学学报”,“Applied Sciences”,“Journal of Sulfur Chemistry”等期刊编委.

    †庆祝《化学学报》创刊90周年.
    谨以此文献给戴立信教授百岁生辰!
  • 基金资助:
    受国家自然科学基金(22171206); 浙江省自然科学基金(Z23B020002)

Recent Advances in the Transformation of Difluorocyclopropenes

Huang Jiapiana, Liu Feia, Wu Jiea,b()   

  1. a School of Pharmaceutical and Chemical Engineering & Institute for Advanced Studies, Taizhou University, Taizhou 318000, China
    b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
  • Received:2023-03-21 Published:2023-04-20
  • Contact: *E-mail: jie_wu@fudan.edu.cn
  • About author:
    †Dedicated to the 90th anniversary of Acta Chimica Sinica.
    Dedicated to Professor Li-Xin Dai on the occasion of his 100th birthday.
  • Supported by:
    National Natural Science Foundation of China(22171206); Natural Science Foundation of Zhejiang Province(Z23B020002)

In recent years, organic reactions involving difluorocyclopropenes have attracted the attention of organic chemists and have made great progress. The reactions mainly include: (1) cyclization: a) transition-metal catalyzed C—H bond activation cyclization with directing groups; b) cyclization reactions with non-directing groups; (2) hydrogenation reduction; (3) fluorination as “F” source reagents. In this paper, the synthesis methods and applications of difluorocyclopropenes in past 10 years are summarized. The conversion reactions of difluorocyclopropenes are emphasized. Additionally, difluorocyclopropenes have aroused considerable interests both from a structural standpoint and their participation in various ring-opening reactions. Given the increasing application of cyclopropyl skeleton in the development of drugs and unarguable importance of fluorinated compounds in medicinal chemistry and agrochemistry, it is no doubt that difluorocyclopropenes are encountered into bioactive molecular and at present lie among “emerging fluorinated motifs”. Although the synthesis and application of structurally diverse difluorocyclopropenes have been witnessed in the past decade, the most widely used methods for the preparation of these compounds include difluoromethylenation of alkynes and difluoromethylation of heteroatom nucleophiles (such as NaF, NaI, nBuN4X, etc.) with a difluorocarbene reagent, which can be generated from various precursors (such as TMSCF3, TMSCF2X, Ph3PCF2CO2-, TFDA, etc.). For the transition metal-catalyzed cyclization of difluorocyclopropenes, some common metal salts (such as rhodium, ruthenium, copper, palladium, silver) are used as catalysts. Moreover, the metallic hydrogen (M—H) reduction strategy is a simple and efficient method for the hydrogenation reduction of difluorocyclopropenes leading to difluorocyclopropanes, and the asymmetric hydrogenation reduction of difluorocyclopropenes can be achieved in the presence of chiral ligands. In fluorination reactions, difluorocyclopropenes have some advantages that cannot be achieved by traditional fluorination reagents for the direct fluorination and functionalization of hydroxyl groups (such as fluorination of polyhydroxyl alcohols). Of course, the biggest disadvantage of difluorocyclopropene as a fluorine source lies in its poor atomic economy, which has been criticized. Despite the remarkable achievements in the reactions of difluorocyclopropenes, there are still many issues that need to be addressed. For instance, difluorocyclopropenes are rarely applied in traditional radical reactions, photocatalysis, electrocatalysis and flow chemistry. Hopefully, difluorocyclopropenes can gradually appear in photo- and electro-catalyzed radical chemistry, and the related asymmetric reactions will also get more attention and development in the near future.

Key words: transition metal-catalyzed, C—H bond activation, cyclization, hydrogenation reduction, fluorination