Copper‐Mediated Aromatic 1,1‐Difluoroethylation with (1,1‐Difluoroethyl)trimethylsilane (TMSCF₂CH₃)

Abstract

A new method for the formation of 1,1-difluoroethyl copper species ("CuCF2 CH3 ") with 1,1-difluoroethylsilane (TMSCF2 CH3 ) has been developed. The "CuCF2 CH3 " species can be applied to the efficient 1,1-difluoroethylation of diaryliodonium salts under mild conditions, affording (1,1-difluoroethyl)arenes in good to excellent yields. This convenient procedure tolerates a wide range of functional groups and thus serves as a practical synthetic tool for the introduction of CF2 CH3 group(s) into complex molecules.

Nickel‐Catalyzed 1,1‐Difluoroethylation of (Hetero)aryl Halides with 1,1‐Difluoroethyl Chloride (CH3CF2Cl)

“…However, the 1,1‐difluoroethylation reaction assisted by transition metals has been relatively less developed owning to the low availability of 1,1‐difluoroethylating reagents. Hu and co‐workers reported a copper‐mediated aromatic 1,1‐difluoroethylation with Me 3 SiCF 2 CH 3 via “CuCF 2 CH 3 ” . Yamakawa and Zhang groups reported cobalt‐ and iron‐catalyzed difluoroalkylation of aryl Grignard reagents with CH 3 CF 2 Br, respectively (Scheme B).…”

“…Hu and co-workers reported a copper-mediated aromatic 1,1difluoroethylation with Me 3 SiCF 2 CH 3 via "CuCF 2 CH 3 ". [12] Yamakawa [13a] and Zhang [13b] groups reported cobalt-and ironcatalyzed difluoroalkylation of aryl Grignard reagents with CH 3 CF 2 Br, respectively (Scheme 1B).…”

Direct C−H Difluoroalkylation of Heteroarenes with Difluoroalkyl Carboxylic Acids

“…Yamakawa reported cobalt‐catalyzed difluoroethylation of aryl Grignard reagents with MeCF 2 Br [12] . Hu groups developed a copper‐mediated difluoroethylation of diaryliodonium salts using Me 3 SiCF 2 CH 3 [13] . More recently, Baran and co‐workers reported nickel‐catalyzed radical cross‐coupling of aryl zinc reagents with fluoroalkyl sulfones [14] .…”

Copper-based fluorinated reagents for the synthesis of CF2R-containing molecules (R ≠ F)

“…Phen: 1,10-phenanthroline. molecules, Wang, Hu and co-workers demonstrated the possibility to use 1,1-difluoroethylsilane (TMSCF 2 CH 3 ) as a precursor for the in situ generation of the corresponding CuCF 2 CH 3 species [64]. The synthetic utility of this copper-based reagent was illustrated through the 1,1-difluoroethylation of diaryliodonium salts, leading to the corresponding (1,1-difluoroethyl)arenes in moderate to high yields (Scheme 13).…”