Recent Progress on the Synthesis of CF 2 H-Containing Derivatives

Noam Levi, Dafna Amir, Eytan Gershonov, Yossi Zafrani

Research output: Contribution to journalReview articlepeer-review

65 Scopus citations


Recent years have witnessed a growing interest in the development of novel synthetic methods and new reagents for the synthesis of difluoromethylated compounds. Dozens of studies have been published on this topic each year over the past few years. These studies are focused on direct and indirect difluoromethylation of various organic functionalities via nucleophilic-, electrophilic-, radical-, carbene-or metal-mediated mechanisms. The present short review covers the very recent studies, published between mid-2017 and early 2019, on the synthesis of compounds containing a CF 2 H group. A brief summary of the physicochemical properties and medicinal applications of difluoromethylated compounds is also included. 1 Introduction 2 Nucleophilic Difluoromethylation 2.1 Metal-Mediated Nucleophilic Difluoromethylation 2.2 Non-Metal Difluoromethyl Nucleophiles 3 Radical Difluoromethylation 3.1 Metal-Induced Radical Difluoromethylation 3.2 Non-Metal-Induced Radical Difluoromethylation 3.3 Electrochemically Induced Radical Difluoromethylation 4 Carbene-Based Difluoromethylation 4.1 Metal-Induced Carbene Difluoromethylation 4.2 Non-Metal-Induced Difluoromethyl Carbenes 5 Cross-Coupling Difluoromethylation 5.1 Palladium-Catalyzed Difluoromethylation 5.2 Nickel-Catalyzed Difluoromethylation 5.3 Copper-Mediated Difluoromethylation 5.4 Iron-Catalyzed Difluoromethylation 5.5 Gold-Mediated Difluoromethylation 6 Electrophilic Difluoromethylation 7 Other Examples 7.1 A Difluoromethyl-Borane Complex 7.2 A Tellurium Difluoromethyl Derivative 8 Summary.

Original languageEnglish
Pages (from-to)4549-4567
Number of pages19
JournalSynthesis (Germany)
Issue number24
StatePublished - 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2019 Georg Thieme Verlag. All rights reserved.


  • carbenes
  • difluoromethylated compounds
  • difluoromethylation
  • electrochemistry
  • nucleophiles
  • radicals


Dive into the research topics of 'Recent Progress on the Synthesis of CF 2 H-Containing Derivatives'. Together they form a unique fingerprint.

Cite this