Tandem Radical Cyclization for the Construction of Difluoro‐Containing Oxindoles and Quinoline‐2,4‐diones

Abstract

Cu-catalyzed direct difluoromethylation of activated alkenes through a difluoromethyl radical addition/cyclization to afford difluorinated oxindoles and quinoline-2,4-diones has been developed. This method provides convenient access to a variety of oxindoles and quinoline-2,4-diones under mild conditions via a proposed tandem radical cyclization process, while tolerating various functional groups well. Moreover, a facile method to construct diverse difluorinated quinoline-2,4-diones by visible-light photoredox catalysis under mild conditions was presented.

Copper-Catalyzed Difluoroalkylation Reaction

“…In 2018, Shi’s group established a facile method to construct diverse difluorinated quinoline-2,4-diones via the Cu-catalyzed direct difluoromethylation of activated alkenes. A difluoromethyl radical addition/cyclization reaction mechanism was indicated for this strategy ( Scheme 2 ) [ 32 ]. It is worth noting that this reaction could also be carried out in the presence of a visible-light photo-redox catalysis.…”

Visible-light-induced radical cascade reaction to prepare oxindoles via alkyl radical addition to N-arylacryl amides

“…[8][9][10][11] Therefore, the search for novel and efficient methods for the preparation of oxindoles has attracted continuous attention from organic chemists. [12][13][14][15][16][17][18][19][20][21] For instance, Lautens and coworkers 22 have established elegant transition metal-catalyzed approaches towards the oxindole core. Usually, the substrates have to be prefunctionalized at the ortho-position of the aromatic ring [23][24][25][26][27] or chloroformamides 28,29 are employed as the substrates (Scheme 1a).…”

Promising reagents for difluoroalkylation

“…It is noteworthy that visible-light photoredox catalysis was also effective for this reaction. 48 Chroman-4-ones are an important motif in medicinal compounds and biologically active molecules. [49][50][51] In 2019, the Zhou group described a visible-light photoredox-catalyzed radical cascade cyclization of alkenyl aldehydes with BrCF 2 COR for the synthesis of various difluoroacetylated chroman-4-ones (Scheme 8).…”