New Synthesis of 2‐Heteroarylperfluoropropionic Acids Derivatives by Reaction of Azine N‐Oxides with Hexafluoropropene

Abstract

Hexafluoropropene reacts with aromatic azine N-oxides under mild conditions to produce fluorides of 2-heteroarylperfluoropropionic acids. The reaction proceeds as 1,3-dipolar cycloaddition followed by spontaneous scission of the N--O bond in the isoxazolidine ring and elimination of HF. When the reaction is carried out in the presence of alcohols or N-alkyl anilines, the in situ formed acyl fluorides give the corresponding esters and amides. They can be also treated separately with nucleophiles to produce the respective acylation products, whereas their hydrolysis leads to unstable carboxylic acids that undergo spontaneous decarboxylation to 1-aryl-1,2,2,2-tetrafluoroethanes. This new reaction provides a simple and general method of synthesizing 2-heteroarylperfluoropropionic acid derivatives that were previously unknown and unavailable.

Recent progress in the use of fluoroorganic compounds in pericyclic reactions

“…The synthetic implications of the revised mechanism were exemplified by a 3-component reaction for a broad variety of N-heterocyclic N-oxides, fluorinated dipolarophiles and nucleophilic quenches. 109 The thermal cycloadditions of the difluoromethylenecyclopropane 72 with nitrones give spiro heterocycloadducts, which can rearrange, in one pot, into highly substituted difluorinated tetrahydropyridinols (Scheme 46). 111 …”

“…108 The cycloadditions of N-heterocyclic N-oxides and hexafluoropropene 68a have been re-investigated and its synthetic scope expanded. 109 The cycloaddition of quinoline N-oxide and 68a in the protic solvent, methanol, gives exclusively the methyl ester 69 (Scheme 45A). The authors noted that this observation is not consistent with the mechanism previously proposed by Banks and co-workers, 110 who suggested a direct collapse of 70 into the end product with elimination of difluorophosgene (Scheme 45B, route I).…”

“…The authors noted that this observation is not consistent with the mechanism previously proposed by Banks and co-workers, 110 who suggested a direct collapse of 70 into the end product with elimination of difluorophosgene (Scheme 45B, route I). A modified mechanism has thus been put forward, 109 which involves the elimination of fluoride to form the acid fluoride 71 (route II), instead of expulsion of difluorophosgene. Facile hydrolysis and decarboxylation in situ afford the final product, as observed by Banks.…”

Multicomponent Access to Functionalized Mesoionic Structures Based on TFAA Activation of Isocyanides: Novel Domino Reactions

“…[11] The overall anionic domino reaction consists of an orchestrated series of events in which electrophilic and nucleophilic species are precisely engaged to guarantee the formation of the C-C, C-N and C-O bonds. Several features of this mechanism remain hypothetical.…”

First synthesis of the N(1)-bulky substituted imidazole 3-oxides and their complexation with hexafluoroacetone hydrate

“…For instance, they react smoothly with cycloaliphatic thioketones, 1a isocyanates, 1b hexafluoropropene, 6 and dimethyl acetylenedicarboxylate (DMAD) 1b yielding imidazoline-2-thiones, 2-aminoimidazoles, 2-(fluoroalkyl)imidazoles, and 2-oxobutanoates, respectively. In all these reactions, cascade processes start with [2+3]-cycloaddition step and subsequent re-aromatization of the heterocycle ring results in the formation of a corresponding C(2)-functionalized imidazole derivative.…”