Silver-catalyzed oxidative decarboxylation of difluoroacetates: efficient access to C–CF₂ bond formation

Abstract

A mild, versatile and efficient method for the silver(I)-catalyzed oxidative decarboxylative gem-difluoromethylenation has been developed. The radical cascade reaction comprises the addition of an oxidatively generated difluoromethylene radical to the isonitrile functionality and subsequent homolytic aromatic substitution. It provides a novel and efficient access to the C-CF2 bond formation.

Synthesis of 1‐Difluoroalkylated Isoquinolines via Palladium‐Catalyzed Radical Cascade Difluoroalkylation–Cyclization of Vinyl Isocyanides with Bromodifluoroacetic Derivatives

“…Among these many different methods, the palladium-catalyzed single-electron transfer (SET) pathway has attracted considerable attention. We also investigated av ariety of differentm onodentate and bidentate phosphorus ligands in this reaction, but found that none of these ligandsl ed to an improvement in the yield of 3a (entries [8][9][10][11][12]. [13b] With this in mind, our own investigation began with the reactiono fv inyl isocyanide (1a) with ethyl bromodifluoroacetate( 2)u nder similar reactionc onditions (Table 1, entry 1).…”

“…Inspired by this result, we screened this reaction against several other palladium salts (entries 2-7), and the resultsr evealed that Pd(OAc) 2 gave the highesta ctivity,p roviding 3a in 39 %y ield. We also investigated av ariety of differentm onodentate and bidentate phosphorus ligands in this reaction, but found that none of these ligandsl ed to an improvement in the yield of 3a (entries [8][9][10][11][12]. Various other Scheme1.Synthesis of difluoroalkylisoquinolines.…”

“…There are currently very few methods availablef or the synthesis of 1-difluoroalkylisoquinolines. [10] Despite considerable progressi nt his area, there has only been one reported synthesis of a1 -difluoroalkyl isoquinoline. The research groups of Qing [9a] and Mikami [9b, c] subsequently reported the transition metal-catalyzed crosscouplingo f1 -iodoisoquinolinew ithd ifluoromethylation reagentsf or the construction of 1-difluoromethylisoquinoline (Scheme1b).…”

“…Most recently,W an and Hao'sg roup reported the synthesis of 1-(difluoro(phenyl)methyl)isoquinoline via the Ag Icatalyzed oxidative decarboxylationr adical cascade reactiono f potassium 2,2-difluoro-2-phenylacetate with ethyl 2-isocyano-3,3-diphenylacrylate (Scheme 1c). [10] Despite considerable progressi nt his area, there has only been one reported synthesis of a1 -difluoroalkyl isoquinoline. The developmento fageneral procedure for the synthesis of ad iverse range of poly-substituted 1-difluoroalkyl isoquinolines therefore remains highly desirable.…”

Visible‐Light‐Induced, Manganese‐Catalyzed Tandem Cyclization of 2‐Biphenyl Isocyanides with Cyclopropanols for the Synthesis of 6‐β‐Ketoalkyl Phenanthridines

“…[14] Therefore, the synthesis of phenan-thridine derivatives is great significance and has drawn much attention in recent years. A great number of radical precursors have been investigated to provide various 6-position functionalized phenanthridines, including alkylation, [12c,15] fluoroalkylation, [16] arylation, [17] phosphorylation, [18] aroylation, [19] carboxylation, [20] and silylation, [21] etc. For example, a range of 6alkylated phenanthridines were prepared through oxidative cyclization of 2-biphenyl isocyanides with various alkyl radical precursors (Scheme 1a), [12c,15] such as alkyl boronic acids, alkyl bromides, ethers, alkanes, alcohols, alkyl acyl peroxides, 1,3dicarbonyl compounds, alkyl trifluoroborates, CF 3 reagents, etc.…”