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

Abstract

Recent advances in formal C(sp2)–H functionalization of aldehyde‐derived N,N‐dialkylhydrazones (substitution at the azomethine carbon atom) are highlighted, with a focus on radical‐mediated processes that open up new opportunities for C–C bond formation, such as alkylation reactions with the aid of hypervalent iodonium reagents or polyhaloalkanes, as well as for carbon–heteroatom bond formation (C–N, C–P). Cascade sequences based on these reactions, and leading to (hetero)cyclic frameworks, are also discussed.

Photoinitiated Three-Component α-Perfluoroalkyl-β-heteroarylation of Unactivated Alkenes via Electron Catalysis

“…Recently, radical α-C(sp 2 )–H functionalization in N , N -dialkylhydrazones has gained attention (Scheme 1b). 4,5 In such cases, the adduct aminyl radical gets SET-oxidized, and deprotonation finally restores the C=N bond resulting in an overall oxidative C–H functionalization. The Minisci reaction, where the C=N double bond is part of a heteroarene, is a well-established and synthetically useful 6 radical process comprising an addition step onto a C=N bond (Scheme 1c).…”

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

“…(E)‐1‐(4‐bromophenyl)‐2,2,2‐trifluoro‐N‐morpholinoethan‐1‐imine ( 2 c ) [21,25,26,37] . The compound 2 c was prepared according to general procedure 2 using 1 c (135 mg, 0.5 mmol) and the crude product was purified by column chromatography to afford 2 c as a yellow oil.…”

“…2 c). [21,25,26,37] The compound 2 c was prepared according to general procedure 2 using 1 c (135 mg, 0.5 mmol) and the crude product was purified by column chromatography to afford 2 c as a yellow oil. Yield: 121 mg (0.36 mmo; 72 %); 1 2 d).…”

α-Functionalization of Imines via Visible Light Photoredox Catalysis

“…The first intermolecular photocatalytic radical addition was published in 2017 by Molander's group [8]. The design of a general and modular approach based on the swift single-electron oxidation of ammonium alkyl bis(catecholato)silicates enabled the alkylation of different N-sulfonyland N-aryl-imines (Scheme 3, top left) [9]. In addition, Friestad employed these silicon reagents to perform the alkylation of N-acyl hydrazones in the presence of a Lewis acid (Scheme 3, top right) [10].…”