Copper-Catalyzed C(sp²)–H Difluoroalkylation of Aldehyde Derived Hydrazones with Diboron as Reductant

Abstract

An efficient and general method for C(sp(2))-H difluoroalkylation of aldehyde derived hydrazones via a Cu(II)/B2pin2-catalyzed reaction between difluoroalkyl bromides and hydrazones was developed. In this reaction, both aromatic and aliphatic difluoroalkylated aldehyde derived hydrazones could be achieved in good to excellent yields. For some heteroaromatic aldehyde derived hydrazones, two fluoroacetates could be introduced onto the final products. A preliminary mechanism study manifested that a difluoroalkyl radical via SET pathway was involved in the reaction. In addition, the catalytic diboron reagent plays an indispensable role in this transformation.

Stereoselective access to trisubstituted fluorinated alkenyl thioethers

“…These observations along with the formation of diphenyldisulfide previously reported suggest that a radical mechanism is involved in the process. These conclusions are consistent with the recent studies of fluorination of hydrazones with analogous copper systems 28,29 and with similar radical reactions mediated by copper. [30][31][32] To identify the key players in the radical formation, the trapping by TEMPO was further examined under various conditions (Table 3).…”

Catalytic asymmetric radical aminoperfluoroalkylation and aminodifluoromethylation of alkenes to versatile enantioenriched-fluoroalkyl amines

“…We were naturally eager to extend the methodology to other fluoroalkylsulfonyl chlorides as radical precursors for the synthesis of the potentially useful chiral β-difluoromethyl or difluoroacetyl amines. To our delight, the reaction of N -alkenyl urea substrate 1a with 2b under the otherwise identical reaction conditions delivered difluoroacetyl-containing product 4A in 97% yield with 85% ee, which containing an acetyl structure is especially appealing because further transformations of the acetyl group in the obtained product would give access to a more diverse class of structures5960. Further improvement of the stereoselectivity indicated that lowering the reaction temperature was obviously beneficial for such a process, giving 4A in 95% yield with 97% ee at 0 °C (Table 3).…”

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

“…Another important feature associated with these reactions is the fact that only aromatic‐aldehyde‐derived hydrazones are generally well accommodated, whereas aliphatic aldehyde derivatives remain challenging substrates that typically show a poorer performance if any. It is also notable that, so far, other azomethine‐derived radical acceptors (i.e., imines, oximes, and oxime ethers) remain reluctant to participate in these reactions , , , , . However, this research is still in its infancy and, looking to the future, we expect to see a rapid expansion in the choice of readily available or suitably designed coupling partners with promising new applications, notably directed toward the construction of complex polycyclic frameworks.…”

“…Soon after these works were reported, Song and co‐workers published a similar process based on the use of catalytic CuBr 2 in the presence of 4,4′‐di‐ tert ‐butyl bipyridine (dtbpy) as a ligand and bis(pinacolato)diboron (B 2 Pin 2 ) as a reductant. A [Cu I ‐Bpin] complex was proposed as the actual active catalytic species.…”