Chinese research in organofluorine chemistry

Nickel(0)-Catalyzed Fluoroalkylation of Alkenes, Alkynes, and Aromatics with Perfluoroalkyl Chlorides

“…Both the inhibition experiments and the formation of tetrahydrofuran derivatives from the reaction with diallyl ether indicated that the perfluoroalkyl radical might be involved in the reaction mechanism. The most likely explanation of generation of R F • is that R F Cl, quite similar to R F I, − accepts one electron from Ni(0) complex, produced by reaction of nickel dichloride with zinc and triphenylphosphine, then dissociated to give R F • and Cl - . The R F • adds to alkene to form intermediate A .…”

“…Recently, however, some reductive systems were found to be more effective. For example: metals, transition metals, , and inorganic reductants as well as redox systems such as Cu, , Zn, Mg, Ni, Fe, Pd, , Pt, Fe(CO) 4 , Na 2 S 2 O 4 , thiourea dioxide, (NH 4 ) 2 S 2 O 8 /HCO 2 Na, CrCl 3 /Fe, Co(II)/Zn, etc. were successfully applied to this reaction.…”

“…The results obtained by using these initiators can be rationalized in terms of single electron-transfer (SET) mechanism. , Unfortunately, all these initiation systems cannot be applied to perfluoroalkyl chlorides (R F Cl) because of their stronger carbon−chlorine bonds. In fact, α -, ω -chloroperfluoroalkyl iodides [Cl(CF 2 ) n I, n ≥ 2] have been used as substrates in the reaction: the iodine being attacked, while the chlorine inert. − It was not until very recently that this problem has been partially solved: using dimethyl sulfoxide (DMSO) as a solvent instead of CH 3 CN/H 2 O in Na 2 S 2 O 4 /NaHCO 3 initiation system (so-called sulfinatodehalogenation reaction), perfluoroalkyl chlorides, ethyl chlorofluoro-, chlorodifluoroacetates, even nonfluorinated compounds, such as ethyl dichloro-, chloroacetates and chloroform, can either be converted to the corresponding sulfinate salts or alkylate alkenes, alkynes, and aromatics . The tremendous role of solvent encouraged us to further reexamine the perfluoroalkylation of organic compounds with perfluoroalkyl chlorides by means of varous metals in different solvents.…”

Synthesis of 2-trifluoromethyl benzimidazoles, benzoxazoles, and benzothiazoles via condensation of diamines or amino(thio)phenols with CF3CN

“…In this regard, several synthetic methods have been introduced in the past decade for the construction of 2-trifluoromethyl benzimidazoles, 14–21 because the introduction of a trifluoromethyl group can improve physicochemical properties, metabolic stability, and binding potency. 22–26 Among the strategies developed, Phillips condensation with o -arylenediamine and trifluoroacetic acid was most commonly used to access 2-(trifluoromethyl)benzimidazoles (Scheme 1a). 27,28 Some of these approaches necessitate the use of reagents or starting materials that are either expensive or require multiple steps for their synthesis, and the reactions are performed under strongly acidic conditions, thereby limiting their synthetic versatility.…”

An alternative metal-free amination approach to 3-trifluoromethyl aniline derivatives: the major products under Kröhnke pyridine synthesis conditions

“…15 This is probably due to the fact that the introduction of the trifluoromethyl group (–CF 3 ) into aniline scaffolds can enhance metabolic stability, lipophilicity, bioavailability, and hydrolytic stability. 16–18…”