C–H Difluoroalkylation of Aldehyde Hydrazones with Functionalized Difluoromethyl Bromides under Copper Catalysis

Abstract

The Cu-catalyzed direct difluoroalkylation of aldehyde hydrazones with functionalized difluoromethyl bromides is described. The reaction yields stereodefined α,α–difluoro-β-keto hydrazones under mild conditions and can be carried out at a scale that opens up the possibility of practical applications.

Nickel‐Catalyzed Carbofluoroalkylation of 1,3‐Enynes to Access Structurally Diverse Fluoroalkylated Allenes

“…[12] To gain some insight into the mechanism of this reaction, we carried out as eries of control experiments.F irst, the subjection of 1.0 equivalents of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) to the standard reaction conditions completely inhibited the reaction (Scheme 3a), and the coupling product 10 between TEMPO and difluoroalkyl radical was detected in 14 and 18 %yield, respectively,with or without the addition of 1a. [13] Both results indicated that ar adical pathway was possibly involved. To further confirm this speculation, the radical clock 11 was subjected to the standard reaction conditions,giving the ring-opening product 12 in 25 %yield (Scheme 3b), thus further demonstrating that af ree difluoroalkyl radical was generated in the catalytic cycle.…”

“…To further improve the yield and considering the ligands coordinating onto the catalyst could tune its activity,s everal ligands (L1-L8)h ad been examined in this reaction system, but L1 still proved to be the optimal (entries 5-11). Further catalyst screening indicated that NiCl 2 ·6 H 2 O, NiCl 2 (dppe), NiCl 2 ·DME, and NiBr 2 (PPh 3 ) 2 could afford comparative yields,a nd Ni(NO 3 ) 2 ·6 H 2 O [8c] turned out to be the best choice (entries [12][13][14][15][16][17][18][19]. Notably, aslight increase of 2a to 2.0 equivalents (1a/2a/3a= 1.5:2:1) further improved the yield of 4a to 93 %( entry 20).…”

Difluoromethylation Reactions of Organic Compounds

“…[115] Finally,o xidation of aminyl radical F by gold species D followed by deprotonation affords the desired difluoromethylated product G. Thea uthors [113] also showedb yD FT calculations that products with the C=Nb ond in E configurationa re lower in energy than those with Z configuration, and that isomerization activation energy usually amountst om ore than 20 kcal mol À1 .T he Au photocatalyst favors formation of the thermodynamic E-configured product. Boyssi, Monteiro and collaborators [116] have recently reported on the CÀHd ifluoroalkylation of aldehyde hydrazones with BrCF 2 CO 2 Et under Cu catalysis. The protocol employs CuCl, 1,10-phenanthroline as ligand, K 2 CO 3 as base in MeCN as solvent at 80 8C.…”

Gem‐Difluorination of Triazole Alkyl Functionalized Amino Pyrazoles by Selectfluor to Access 4,4‐Difluoro‐pyrazol‐3‐ones/Pyrazol‐3‐imines

“…Several research groups reported the synthesis of mono fluorinated and difluorinated pyrazoles (Figure ) . In 2014, Sandford and co‐workers pioneered the synthesis of difluorinated pyrazoles under microwave irradiation condition, and obtained a mixture of mono‐ and di‐fluorinated compounds in low yield (Figure a).…”

“…Several research groups reported the synthesis of mono fluorinated [7][8][9][10] and difluorinated pyrazoles ( Figure 2). [11][12][13][14][15][16][17][18] In 2014, Sandford and co-workers [16] pioneered the synthesis of difluorinated pyrazoles under microwave irradiation condition, and obtained a mixture of mono-and di-fluorinated compounds in low yield (Figure 2a). Walton [17] reported the single example of difluorinated pyrazole compound under thermal difluoro pyrazol-3-imines derivatives in high yield.…”