Silver-promoted decarboxylative radical addition/annulation of oxamic acids withgem-difluoroolefins: concise access to CF₂-containing 3,4-dihydroquinolin-2-ones

Abstract

Described is a silver-promoted decarboxylative radical addition/annulation of oxamic acids with gem-difluoroalkenes enabling the convenient synthesis of various structurally diverse CF2-containing 3,4-dihydroquinolin-2-ones that might find applications in medical chemistry.

Silver-Catalyzed Decarboxylative Radical Addition/Cyclization of Oxamic Acids with Alkenes towards Quinolin-2-ones

“…Based on the present results and related reports in the literature, 6,[10][11][12] a plausible reaction mechanism is proposed as shown in Figure 2. First, Ag(I) is oxidized by persulfate anion to form Ag(II), which then triggers a single-electrontransfer process of the N-aryloxamic acid 1 to regenerate the Ag(I) and form the N-arylcarbamoyl radical A with release of CO 2 .…”

“…11 Liu and co-workers recently reported an approach to the construction of CF 2 -containing 3,4-dihydroquinolin-2-ones through the decarboxylative radical addition/cyclization of oxamic acids with gem-difluoroolefins (Scheme 1b). 12 Despite the advances made in this area, the scope of the alkene substrates is very limited and considerable challenges remain in the reactions of electron-rich olefins with N-arylcarbamoyl radicals and in the synthesis of 3,4-unsubstituted quinolinones by a radical pathway. We recently filed two patents on the preparation of 3,4-dihydroquinolin-2(1H)-ones from oxamic acids by Ag catalysis.…”

Cu(II) Catalyzed Unsymmetrical Di-oxidation of gem-Difluoroalkenes to Generate α,α-Difluorinated-α-Phenoxyketones, an Unstudied Substructure

“…This regioselective attack of the radical to the difluorinated position is consistent with other radical functionalization reactions of alkenes. [27,28,33,[43][44][45] Trapping of radical 11 with Cu I Cl and molecular oxygen affords peroxo intermediate 12. Concerted elimination of Cu II oxide 12 might afford product 3 and Cu I Cl(OH) 13, [40,41,46,47] which could react with HCl to regenerate the active catalyst Cu II Cl2.…”

Fluorine-Retentive Strategies for the Functionalization of gem-Difluoroalkenes

“…In one case, an Ag-promoted decarboxylation of oxamic acid derivatives initiated a radical cascade to functionalize gem-difluoroalkenes and generate 3,4-dihydroquinolin-2-ones (Scheme 35). 75 This reaction likely proceeded through initial persulfate-mediated oxidation of Ag I to Ag II , which promoted the decarboxylation of the oxamic acid derivative to generate a carbamoyl radical 217 (Scheme 35B). This radical added into the gem-difluoroalkene to generate benzyl radical 218 that then underwent an intermolecular 6-endotrig cyclization with the appended arene to generate aryl radical 219.…”