Replacement of the carboxylic acid function with fluorine

Abstract

Replacement of a carboxyl function by fluorine, fluorodecarboxylation, is a new process that can be accomplished by the reaction of alkanoic acids with xenon difluoride. Primary, tertiary, and benzylic acids perform best in the reaction, which is conducted at room temperature in methylene chloride or chloroform solution. A reaction mechanism is proposed in which the acid is initially converted to a fluoroxenon ester, RCO2XeF. The esters of the primary and secondary acids react by nucleophilic displacement by fluoride, as evidenced by incorporation of 18F− and no reactions common to free radicals or carbocations. The esters of the tertiary and benzylic acids react by converting to free radicals that can be further oxidized to carbocations. Thus incorporation of 18F− and racemization are observed with α-methoxy-α-trifluoromethylphenylacetic acid. Hydroxyl and amino functions inhibit the reaction. Aromatic and vinylic acids do not react.

Einführung von Fluor und fluorhaltigen funktionellen Gruppen

“…Eine weitere Synthesemethode für fluormethylierte Ether ist die durch XeF 2 [177] oder Aryldifluor-l 3 -broman induzierte oxidative Umlagerung von Benzylalkoholen (Schema 41) [178] , die unter Phenylgruppenbeteiligung an der Aryl-C-O-Bindungsbildung in der Synthese von Aryl-a-fluormethylethern abläuft. Auch durch elektrophile Fluorierung von O,S-Acetalen [179] oder a-Carboxymethylethern [99,180] lassen sich a-Fluormethylether erhalten. Auf ähnliche Weise kann die C-H-Bindung der Methylgruppe von Methylsulfid mit N-Fluorpyridiniumtriflat zu a-Fluormethylsulfiden oxidiert werden.…”

Xenon difluoride in the organic laboratory: a tale of substrates, solvents and vessels

“…30 In a series of detailed studies Patrick and co-workers had previously shown that reaction of carboxylic acids with XeF 2 in CH 2 Cl 2 solution in polyethylene flasks gave fluorides [RCO 2 H → RF]. [31][32][33] We therefore undertook a comparison of the reactions of carboxylic acids with XeF 2 in (i) CH 2 Cl 2 /PTFE and (ii) CH 2 Cl 2 /Pyrex. 30 Results of these studies are summarised in Table 2.…”

New trends in the chemistry of α-fluorinated ethers, thioethers, amines and phosphines

“…Finally, replacement of the carboxylic acid function with fluorine by means of xenon difluoride also affords fluoromethyl ethers (Scheme 7) [65,66].…”