Recent Progress on Difluoromethylation Methods

Difluoromethylated Difunctionalization of Alkenes under Visible Light

“…The difluoromethyl group (−CF 2 H), the highly polarized C–H bond, thus makes it a superb hydrogen bond donor (Figure a), which usually acts as a bioisostere for alcohol, thiol, and amine functional groups . The incorporation of the CF 2 H group in bioactive molecules such as drugs, herbicides, fungicides, and agrochemicals (Figure b) were studied widely, especially for the formation aryl-CF 2 H bonds. , …”

Copper-Catalyzed Difluoroalkylation Reaction

“…Various catalysts (Pd, [ 7 ] Ir, [ 8 , 9 ] Cu [ 10 ], Ni [ 11 ], etc. [ 12 , 13 ]) have been successfully applied in difluoroalkylation reactions [ 14 , 15 , 16 , 17 , 18 , 19 ]. However, it is still a great challenge to selectively control the catalytic cycle and obtain the desired fluorinated compounds by directly using classical transition-metal-catalyzed cross-coupling reactions, as some difluoroalkyl metal species have significantly different properties from their nonfluorinated analogues.…”

Promising reagents for difluoroalkylation

“…[1][2][3] Therefore, the development of efficient and simple methods for the introduction of difluoroalkyl groups has received more and more attention in recent years. [4][5][6][7][8] At present, various reagents such as HCF 2 Cl, 9 BrCF 2 P(O)(OEt) 2 , 10 TMSCF 2 Br, 11,12 HFPO, 13 CF 3 ZnBr 2 •CH 3 CN, 5 FSO 2 CF 2 CO 2 H 14 and so on 4,[15][16][17][18] are used for difluoroalkylation reactions. But some side reactions such as dimerization, protonation and other unknown byproducts accompany the difluoroalkylation reaction when some of these reagents especially metal species are employed.…”