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

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.