Perfluoroolefins, reaction with nucleophiles

Another interesting and important technique uses reactions of perfluoroolefins with nucleophilic reagents. The peculiar chemical behavior... 

Systemization of experimental data on the syntheses of heterocyclic compounds with perfluoroalkyl groups from perfluoroolefins is based on reactions with various 1,1-, 1,2-, 1,3-, and 1,4-binucleophilic reagents. While the main features of nucleophilic reactions are preserved, further transformations of the primary products (or adducts, or the products of substitution of the functional groups at the internal multiple bond) occur under the influence of the added functional group containing a heteroatom. Here one can expect dramatic differences in the effect of the nature of the nucleophilic reagent between cyclizations by new nucleophilic centers and centers already available in the molecule. Another important aspect is isomerization of the primary internal olefin into the terminal olefin or internal olefin with a different structure under the action of the nucleophilic agent. This may be critical to the structure of the heterocycle formed. 

Oxidation of internal perfluoroolefins by alkaline solutions of hydrogen peroxide and alkaline and alkaline-earth hypohalides leads to the formation of olefin oxides, the yield of the target product being 40-50%. The reaction with sodium hypochlorite in an alkali in the presence of acetonitrile is an example of epoxidation performed by the nucleophilic attack of the OC1-anion of the multiple bond with further elimination of the chloride anion by the intermediate carbanion (79IZY2509, 79IZV2812, 79RP666176,... 

In reactions of primary alkylamines with internal perfluoroolefins, intramolecular nucleophilic cyclization gives a heterocyclic compound with a perfluoroalkyl group. As mentioned above, primary alkylamines can be binucleophilic reagents with nucleophilic centers on the nitrogen atom. Such compounds having an NH2 group form four-membered heterocycles and many polycyclic heterocycles with one nitrogen atom. 

In this case, a mixture of cis- and ra s-perfluoro-4,5-dihydro-2,3,4,5-tetramethyl-4-ethylfurans is obtained. This is a general reaction, which also works with other perfluoroolefins and alcohols. For example, when the tetrafluoroethylene pentamer reacts with allyl alcohol in the presence of bases, the initial reaction is nucleophilic addition at the multiple bond, forming olefin 44, followed by the formation of perfluoro-4-ethyl-2,3,4,5-tetramethyl-4,5-dihydrofuran 45 in the presence of KF (87ASCC31). 

Note that for the synthesis of heterocyclic compounds one need not have an a-b-c triad in the substrate it is essential that the triad be formed in the course of the reaction with perfluoroolefins. This is natural since substituted thioureas must exhibit the same properties as thiourea itself. This was verified by reference to the reaction of perfluoro-2-methyl-3-isothiocyanatepent-2-ene with ammonia. When ammonia attacks the carbon atom of the N=C=S group, a derivative of thiourea having an a-b-c triad is formed subsequent intermolecular cyclization can occur via an attack of the S-nucleophilic centers at the multiple bond, forming isomeric compound 56 (03UP1). 

If the N,S- or Y,Y-binucleophile has an a-b-c triad, the character of the heterocyclic product depends on the nature of the nucleophile initiating the reaction with perfluoroolefins and perfluoroazaalkens (Table Y) (03PU1). 

Using pentaerythritol and 1,3-butanediol as nucleophilic agents under conditions of base catalysis in reactions with perfluoroolefins leads to six-membered heterocycles (in particular, to spiro derivatives of 1,3-dioxane) (96ZOB1995). 

The second type is the construction of a heterocyclic system from units containing perfluoroalkyl groups or their fragments. Each type has its own advantages and weaknesses. Thus, reactive species used in processes of the first type are perfluoroalkyl radicals and carbocations, and the processes are conducted by elaborate methods (thermolysis, photolysis, electrolysis, one-electron oxidation, etc.), whereas reactions of the second type use condensation of molecules with suitable groups and nucleophilic reactions of perfluoroolefins. 

Terminal perfluoroolefins have two fluorine atoms at the double bond. The carbon atoms of the latter bear a significant positive charge, and the nucleophilic agents easily replace the fluorine atoms at the multiple bond. The reactions of binucleophilic reagents with terminal perfluoroolefins form heterocyclic systems. The first step of the reaction involves a nucleophilic attack at the carbon atom of the double bond, generating a carbanion. The latter is stabilized by elimination of the fluoride ion and formation of a new double bond. Subsequent cyclization by the intramolecular attack of the nucleophilic center at the double bond leads to the formation of a heterocyclic system. For example, when a reaction mixture of hexafluoropropylene and sodium dialkylaminodithiocarbamate in dimethylacetamide is heated with aqueous sodium tetraphenylborate, one obtains the tetraphenylborate salt of 2-dialkylamino-4-trifluoromethyl-4,5-difluoro-l,3-dithiolan-2-yl (78JFC(12)193). This compound is formed by intramolecular cyclization of the S-nucleophilic center. 

The reactions of perfluoroolefins with hexafluoroacetone cyanohydrin under conditions of nucleophilic catalysis yield 3-iminotetrahydrofuran. The latter evidently forms via the intermediate carbanion involved in the intramolecular nucleophilic cyclization (91JFC(54)401). This is an example of synthesis following route f. 

The reactions of terminal perfluoroolefins with oA/zo-bifunctional benzenes used as nucleophilic reagents result in the five-, seven-, and nine-membered benzoheterocycles. In this case, aprotic dipolar solvents are generally employed, and the base is triethylamine. Thus the products of the reactions of oA/zosubstituted anilines with terminal perfluoroolefins are five-membered benzoheterocyclic compounds. 

Intramolecular nucleophilic cyclization is used for the synthesis of four-membered heterocycles. This is a general route for reactions of many perfluoroolefins with primary amines. Thus the interaction between perfhioro-3,4-dimethylhex-3-ene and butylamine in the presence of triethylamine forms N-butyl-perfhioro-2,3,4-trimethyl-2-ethyl-l, 2-dihydro-azete (87ASCC31). In the absence of triethylamine, a mixture of products is obtained, among which are the derivatives of azetidine 15 and azete 16. 

These examples demonstrate the utility of bifunctional nucleophiles in reactions of perfluoroolefins with an internal multiple bond leading to various heterocyclic compounds with perfluoroalkyl substituents. 

Syntheses include nucleophilic addition or substitution of a binucleophilic reagent to perfluoroolefins followed by an intramolecular nucleophilic cyclization to afford seven-membered heterocycles. Thus, with the reaction of perfluoro-2-methylpent-2-ene with hydroxylamine, the major product is compound 131, whereas the expected compound 132 is obtained in a low yield (01 JFC(110)11). 

The above examples demonstrate the possibilities for syntheses of various heterocyclic compounds with perfluoroalkyl groups using bifunctional nucleophiles in reactions of perfluoroolefins involving their double bonds. Chambers et al. (79JCS(P1)214) found that the reaction of perfhioro-3,4-dimethylhex-3-ene with ethylene glycol in tetraglyme forms a seven-membered heterocycle, 5-pentafluoroethyl-5,6,7-tris-(tri-fluoromethyl)-l,4-dioxacyclohept-6-ene 133, while with ethanolamine the product is 5-pentafhioroethyl-5,6,7-tris-(trifluoromethyl)-l-oxa-4-azacyclo-hept-6-ene 134. 

With the practical methods for the generation of F-enolates in hand, we next turned attention to the chemistry of F-enolates. The fundamental questions to be answered are as follows, (a) Do F-enolates show the ambident nucleophilic reactivity like hydrocarbon enolates (b) How about the aldol reactivity 7 (c) Do F-enolates exhibit any unique reactivities In other words, do F-enolates show rather the electrophilic reactivity of perfluoroolefins With these questions in mind, we carried out reactions of F-enolates with a wide variety of reagents. 

---