1,2-Bis-perfluoroalkylations of alkenes/alkynes with perfluorocarboxylic anhydrides.

An isoalloxazine (flavin) ring system and a secondary amine have been integrated through a short peptide linker with the aim of using photons as efficiently as possible in photoredox/enamine dual catalysis. We herein report a peptide-bridged flavin−amine hybrid that can catalyze αoxyamination of aldehydes with TEMPO under weak blue light irradiation to achieve an extremely high quantum yield of reaction (Φ = 0.80).

Given the importance of difluoromethylated molecules for drug and agrochemical development, much attention has been drawn to the establishment of related synthetic protocols, as exemplified by the CF2H radical‐mediated catalytic difluoromethylation of alkenes. However, most of these difluoromethylations proceed under photocatalytic conditions, whereas those requiring thermal conditions are few. Herein, we developed a general and practical method of Cu‐catalyzed alkene difluoromethylation with difluoroacetic anhydride (DFAA) as a CF2H source, showing that the thus realized amino‐, allylic‐, and oxy‐difluoromethylations involve bis(difluoroacetyl) peroxide (BDFAP) in situ generated from DFAA and H2O2 and further demonstrating the occurrence of carbo‐difluoromethylation under catalyst‐free conditions. The obtained results pave the way to the simple and efficient synthesis of a broad range of difluoromethylated species and thus facilitate their practical applications, including those in medicinal and agricultural chemistry. Moreover, we probed the mechanisms of the observed transformations, rationalized the extraordinary fast decomposition of BDFAP compared to that of diacyl peroxides containing CF3 or CF2Cl groups, and performed DFT calculations to shed light on the low stability and decomposition mode of BDFAP. Finally, we examined the influence of fluorinated radical philicity on the reaction outcome.magnified image

Acid dissociation constants (pKa) of nine kinds of flavin analogues as molecular catalyst candidates were determined by CZE. Although some of the analogues are instable and degradable under the light exposure or in alkaline aqueous solutions, the effective electrophoretic mobility of the flavin analogue of interest has been measured with the residual substance. The pKa values of the flavin analogues were analyzed through the changes in the effective electrophoretic mobility with varying pH of the separation buffer. One or two steps pKa values were determined by the analysis. One of the degraded species from the flavin analogues, lumichrome, was also detected in the CZE analysis, and its pKa values were also determined. While coexisting impurities generated over the storage conditions were found in some analogues, the pKa values of the target analogues were successfully determined with the help of the CZE separations. A pressure‐assisted CZE was utilized for the determination or the estimation of the pKa values of such analogues as possessing carboxylic acid moiety.