A selective and mild electrochemical defluorinative carboxylation for late-stage C(sp³)–F bond functionalization

Abstract

We report the first general protocol for the electrochemical defluorinative carboxylation of trifluoromethyl (hetero)arenes, and trifluoromethyl – acetates and –acetamides for accessing their highly valuable α,α-difluorocarboxylic acid analogues. Given the...

Selective Defluoroalkylation and Hydrodefluorination of Trifluoromethyl Groups Photocatalyzed by Dihydroacridine Derivatives

“…Trifluoroacetamide and 2-substituted methyl on N-ary (29) give the corresponding target products. 3-substituted pyridine (30), free hydroxyl (31), and 4-substituted free carboxyl groups (32) were also well tolerated. Notably, the introduction of a carboxylic acid group at the fourth position of the N-aryl ring in trifluoroacetamides resulted in the formation of monofluoroalkylation products.…”

“…The existing methods for the selective C–F activation of CF 3 groups can be classified into four categories: (1) Lewis-acid-promoted formation of a difluorocarbocation intermediate; − (2) metal or electrochemical-induced formation of a difluorocarbonanion intermediate; − (3) single electron transfer (SET) or spin-center shift pathways leading to a difluorocarboradical intermediate; − and (4) a carbene strategy catalyzed by rhodium or silver (Scheme a). − Using these strategies, besides defluoroalkylation and hydrodefluorination of trifluoromethylarenes, Zhang’s group reported selective defluoroarylation and Zhang’s group later developed a method for the selective defluorination bifunctionalization of trifluoromethyl aromatics with active alkenes . Although these strategies are now well-established, the selective C–F activation and defluorination functionalization of the CF 3 motif continue to pose challenges due to the high energy of C­(sp 3 )–F bonds and the need to prevent excessive defluorination.…”

Recent Advance in the C−F Bond Functionalization of Trifluoromethyl Aromatic and Carbonyl Compounds

“…Following this, Meanwell demonstrated an electrochemical defluorinative carboxylation method applicable to trifluoromethyl (hetero)arenes, trifluoromethyl-acetates, and trifluoromethyl-acetamides(Scheme 33). [67] A noteworthy feature of this technique is the utilization of finely ground dry ice as the carboxyl source. In the majority of cases, this innovative and efficient defluorinative carboxylation transformation proceeded smoothly, yielding the desired difluorocarboxylic acids in moderate to good yields with outstanding chemoselectivity.…”

A review of frustrated Lewis pair enabled monoselective C–F bond activation

“…Such a synthetic strategy not only allows the installation of CF 3 and CF 2 H units early in the synthetic route but allows direct use of the target compound as a starting material, greatly simplifying the radiosynthesis of fluorine-18 labelled CF 3 and CF 2 H groups in a wide range of chemical settings. 43 …”