Visible-light mediated directed perfluoroalkylation of hydrazones

Abstract

Perfluoroalkylation of N-alkylhydrazones has been achieved via visible light mediated photoredox reactions between the hydrazone and perfluoroalkyl iodide (RI). This protocol provides a convenient and efficient access to a series of perfluoroalkylated aromatic aldehyde hydrazones which tolerates a wide range of functional groups on the aromatic ring, and allows the use different types of primary and secondary perfluoroalkyl iodides with up to eight carbon atoms. Furthermore, aliphatic aldehyde hydrazones and N-monosubstituted hydrazones which are unreactive in previously reported hydrazone perfluoroalkylation reactions now take part in the reaction under our reaction conditions to give a satisfactory yield of products. Stern-Volmer quenching studies and spin-trapping experiments indicated that these reactions proceed by free radical addition of the R radical to the azomethine atom followed by one electron oxidation of the hydrazyl radical and deprotonation of the diazenium cation.

Cu‐Catalyzed C(sp2−H)‐Trifluoromethylation of Aldehyde Hydrazones with Langlois Reagent

“…The involvement of aminyl radicals and nitrenium cations in the free-radical additions to hydrazones is well documented in the literature. [24,25,32]…”

“…[26] The compound 1 f was prepared according to the general procedure using 4-chlorobenzaldehyde (77.7 mg, 0.55 mmol) and 4-aminomorpho- N-morpholinomethanimine (1 g). [32] The compound 1 g was prepared according to the general procedure using 3-bromobenzaldehyde (498 mg, 2.69 mmol) and 4-aminomorpholine (550 mg, 5.39 mmol). Yield: 370 mg (1.37 mmol; 51 %); 1 (E)-1-(4-methoxyphenyl)-N-morpholinomethanimine (1 h).…”

“…(2 a). [21,26,32] The compound 2 a was prepared according to general procedure using 1 a (191 mg, 1.0 mmol) and the crude product was purified by column chromatography to afford 2 a as a yellow oil. Yield: 195 mg (0.75 mmol; 75 %); 1…”

Photoredox Fluoroalkylation of Hydrazones in Neutral and Reductive Modes

“…Since visible light photoredox catalysis can provide very mild conditions for the radical formation, [11] hydrazone fluoroalkylation using iridium [12a,b] and gold [12c] metal complexes, as well as organic photocatalysts, [12d–f] was also documented. Noteworthy, certain hydrazones were reported to react with perfluoroalkyl iodides by direct photoinduced single electron transfer in the absence of any sensitizer [13] .…”

Radical‐Mediated Formal C(sp2)–H Functionalization of Aldehyde‐Derived N,N‐Dialkylhydrazones

“…Later on, Shi and Shen reported a series of perfluoroalkylation reactions with perfluoroalkyl iodides (R f I, with R f = n ‐C 3 F 7 , i ‐C 3 F 7 , n ‐C 4 F 9 , n ‐C 5 F 11 , n ‐C 8 F 17 ) under very similar photocatalytic conditions. Trifluoromethylation reactions were also studied by these authors.…”