Synthesis of Perfluoroalkyl-Substituted Azines via Nucleophilic Substitution of Hydrogen with Perfluoroisopropyl Carbanions

Abstract

Perfluoroisopropyl carbanions generated in situ by treatment of perfluoropropene (HFP) with solid KF in the appropriate solvents add to N-alkylpyridinium, quinolinium, and other azinium salts to give reasonably stable N-alkyldihydroazines containing a perfluoroisopropyl group. In most cases, addition proceeds in position 2 of the heterocyclic ring. Stability of these dihydroazines depends on the nature of the N-alkyl group and other substituents present in the azine ring. The least stable of them were converted into their stable C-trifluoroacetyl derivatives in reaction with trifluoroacetic anhydride. Treatment of N-benzyl- or N-p-methoxybenzyl-2-perfluoroisopropyl dihydroazines with oxidizing agents such as DDQ or cerium(IV) ammonium nitrate results in cleavage of the benzylic C-N bond followed by oxidation of the ring, giving pyridines or quinolines with a perfluoroisopropyl group in the aromatic ring. On the basis of these findings, a new protocol for introduction of perfluoroalkyl substituents into azine rings was elaborated via oxidative nucleophilic substitution of hydrogen. It involves three chemical steps: (i) alkylation of azine with p-MeOC6H4CH2Br, (ii) reaction of the resulting salt with fluorinated carbanions generated in situ from HFP and KF, and (iii) N-deprotection and aromatization of the isolated dihydroazine on treatment with CAN. The first two reactions, (i) and (ii), can be performed as a one-pot operation.

Direct heptafluoroisopropylation of arylboronic acids via hexafluoropropene (HFP)

“…There are only very few other successful examples of heptafluoroisopropylated arenes. [11][12][13][14][15] For example, Ishikawa et al described a method to form heptafluoroisopropylated arenes under ultrasonic irradiation conditions from heptafluoroisopropylhalide. 11 Chen et al reported a synthetic route to heptafluoroisopropylated arenes via pre-prepared copper complexes from heptafluoroisopropylhalide.…”

Functionalization of Bis-Diazaphospholene P-P Bonds with Diverse Electrophiles

“…Functionalization of aryl diazaphospholenes, and structural confirmation of 19 While 9g was unreactive with an aldehyde or imine, exposure of the compound to quinolinium bromide 18 resulted in rapid and complete conversion to compound 19 (equation 3, Scheme 7, structure confirmed by x-ray crystallography). 25 This represents the first reported carbon-carbon bond formation by transfer of a diazaphospholenebound carbon fragment directly to an electrophile.…”

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

“…Its formation results from the presence of water in the substrate, which is a highly hygroscopic compound. In some cases, the reaction performed at room temperature (entries 6,11,12) or over a longer period of time (entry 7) gave comparable or better results compared to the standard conditions.…”

“…salts with CF 3 À [10] or with perfluoroispropyl carbanions, generated in the reaction mixture from hexafluoropropene (CF 2 =CFCF 3 , HFP) and KF (s) . [11] The two crucial steps of these reactions were, nucleophilic addition of the carbanions to the electrophilic homo-or heteroaromatic ring and subsequent aromatisation of the negatively charged s H complexes or neutral dihydroazines upon addition of an oxidant.…”