Five-membered perfluoroalkylation

Particularly alkyl halides which have a perfluoroalkyl group at the /3-position undergo smooth carbonylation. Probably the coordination of fluorine to form a five-membered chelate ring accelerates the reaction. Double carbonylation to give the a-keto amide 915 is possible in Et NH with the fluorine-bearing alkyl iodide 914[769,770]. The ester 917 is obtained by the carbonylation of the /3-perfluoroalkyl iodide 916 in ethanol. 

Perfluoroalkyl-substituted nitriles react readily with various 1,3 dipoles, such as azomethine ylides [755,156,157],azometlune imines [158],diazoalkanes [759],azides [160 161,162], and nitrile ylides [163] to give stable five-membered ring systems (equation 37)... 

III. Introduction of Fluorine and Perfluoroalkyl Groups into Five-Membered Heterocycles via Cyclocondensation Reactions... 

Similarly, with perfluoroalkanoic acids or the corresponding anhydrides, perfluoroalkyl groups can be attached to five-membered heterocyclic systems [81JFC( 18)243] (Scheme 42). 

IV. Introduction of Fluorine, Poiyfluoroaikyl, and Perfluoroalkyl Groups into Five>Membered Heterocycles via Cycloaddition Reactions... 

Fluoro-containing substituents can be introduced regioselectively into five-membered heterocycles by using the enormous synthetic potential of the [3 -I- 2] cycloaddition reaction via the 1,3-dipolar or/and dipolarophilic species. In the latter case fully perfluoroalkyl-substituted five-membered heterocycles become available. 

B. Synthesis of Perfluoroalkyl-substituted Five-Membered Heterocycles via [4-1-1] Cycloaddition Reactions... 

Since perfluoroalkyl-substituted olefins and alkynes possess low-lying frontier orbitals, [4 + 2] cycloaddition reactions to oxazoles and thiazoles without strongly electron-donating substituents are unfavorable. On the other hand, five-membered heteroaromatic compounds possessing an electron-rich diene substructure, like furans, thiophenes, and pyrroles, should be able to add perfluoroalkyl-substituted olefins as well as alkynes in a normal Diels-Alder process. A reaction sequence consisting of a Diels-Alder reaction with perfluoroalkyl-substituted alkynes as dienophile, and a subsequent retro-Diels-Alder process of the cycloadduct initially formed, represents a preparatively valuable method for regioselective introduction of perfluoroalkyl groups into five-membered heteroaromatic systems. 

Electrocyclization reactions of perfluoroalkyl-substituted conjugated 1,3-dipoles (1,5-dipoles) and of heteropentadienyl anions and subsequent elimination with aromatization offer an elegant method for the selective introduction of perfluoroalkyl groups into five-membered heteroaromatic systems [79JCS(Pl)214j. 

The system HSiCM DABCO (DBU) may be used to generate SiCb" which formally acts as a silylene synthon. l,4-Diazabuta-l,3-dienes predominately react to give the five membered heterocycles Obviously this route can be applied both to nucleophilic and electrophilic heterodienes. Similar to the reactions of the 1,3- and 1,4-diazabutadienes, perfluoroalkyl-substituted vinylketones also give five-membered rings. However, in all cases the reaction conditions have to be optimized individually. 

Trialkyl phosphites have been converted to dialkyl chlorophosphates (32) in a mild and efficient way by tellurium tetrachloride. Tris(dimethylamino)phosphine abstracts iodine from 1-iodoperfluoroalkanes to give metal-free perfluoroalkyl anions which have basic but poor nucleophilic properties. The bicyclic phosphite (33) with chlorine gave a sole product (34) resulting from opening of the five-membered and not the seven-membered ring. ... 

The rearrangement mechanisms of 5-perfluoroalkyl-l,2,4-oxadiazoles such as the five-to-six membered ring-rearrangements by hydrazinolysis and the photoinduced competitive rearrangements have been investigated <06JOC8106 06JOC2740>. 

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