Synthesis of <i>gem</i> ‐difluoroalkenes via cross‐coupling reactions of 2,2‐difluoroethenyl ( <scp> CF ₂ </scp> <scp>CR</scp> ) and 2,2‐difluoroethenylidene ( <scp> CF ₂ </scp> C) building blocks

Abstract gem ‐Difluoroalkenes are an important class of compounds in organofluorine chemistry because they can be used to develop biologically active substances, such as enzyme inhibitors, anticancer and antiviral drugs, and other bioactive molecules. Among various methods for preparing gem ‐difluoroalkenes, palladium‐catalyzed cross‐coupling reactions of nucleophilic 2,2‐difluoroethenyl (CF 2 CR) and 2,2‐difluoroethenylidene(CF 2 C) building blocks, such as organoboron, organozinc, organostannane, and organosilane reagents, with aryl, alkenyl, alkynyl, and acyl halides offer a straightforward and efficient pathway for constructing gem ‐difluoroalkenes through carbon–carbon bond formation. These building blocks can be easily prepared from commercially available starting materials, such as 2,2,2‐trifluoroethyl tosylate (CF 3 CH 2 OTs). Since 2,2‐difluoroethenylboron and 2,2‐difluoroethenylzinc reagents are only stable in solution, synthesis of gem ‐difluoroalkene via their cross‐coupling reaction is limited. However, the use of isolable 2,2‐difluoroethenylstannane and 2,2‐difluoroethenylsilane reagents in their cross‐coupling reactions overcomes synthetic limitations associated with 2,2‐difluoroethenylboron and 2,2‐difluoroethenylzinc reagents. Electrophilic 2,2‐difluoroethenylidene building blocks, including dibromides, iodides, and tosylates, are also useful counterparts in palladium‐catalyzed cross‐coupling reactions to afford various gem ‐difluoroalkenes. Advances in the preparation and reaction of these reagents will be discussed, focusing on their application in forming carbon–carbon bonds with various electrophiles and nucleophiles.