Fluoroalkenes synthesis

Souzy, R., Ameduri, B., Boutevin, B., Capron, P., Marsacq, D., Gebel, G. (2005) Protonconducting polymer electrolyte membranes based on fluoropolymers incorporating perfluorovinyl ether sulfonic acids and fluoroalkenes synthesis and characterization. Fuel Cells, 5, 383 397. 

The introduction of a fluorine atom to bioactive compounds can modify their activity, so much effort has been invested in the development of selective fluorination reactions. Many bioactive compounds that have double bonds are known, and their analogs, which have a fluorine atom at their double bond, have been attracting the attention of biochemists and organic chemists [ 1 -4-]. In order to induce an effect on the activity of bioactive compounds, a fluorine atom must be introduced to the desired position at the double bond with the correct stereochemistry. The stereoselective synthesis of fluoroalkene is therefore important. There have been articles written recently that concern fluoroalkene synthesis [5-7] so I would like to introduce the recent development in the stereoselective synthesis of mono-fluorinated alkenes. 

Scheme 17 Stereoselective fluoroalkene synthesis by Negish coupling using 1-bromo-l-fluoro-l-aUcene 42h...

Reaction of perfluoroaLkenes and hypochlorites has been shown to be a general synthesis of perfluoroepoxides (32) (eq. 7). This appears to be the method of choice for the preparation of epoxides from internal fluoroalkenes (38). Excellent yields of HFPO from hexafluoropropylene and sodium hypochlorite using phase-transfer conditions are claimed (34). 

The direct oxidation of fluoroalkenes is also an excellent general synthesis procedure for the preparation of perfluoroepoxides (eq. 8). This method exploits the low reactivity of the epoxide products to both organic and inorganic free radicals. 

For the synthesis of the title compound, Oxone or 3-chloroperbenzoic acid2 can be used to oxidize the sulfide to the sulfone. The title compound is a key reagent for the preparation of fluoroalkenes from aromatic11 and aliphatic2 aldehydes. Recently, a stereospecific method to (E)- and (Z)-fluoroalkenes was reported using this reagant.12 13 14... 

REACTION OF SULFOXIDES WITH DIETHYLAMINOSULFUR TRIFLUORIDE PREPARATION OF FLUOROMETHYL PHENYL SULFONE, A REAGENT FOR THE SYNTHESIS OF FLUOROALKENES (Benzene, [(fluoromethyl)sulfonyl]-)... 

Electron-withdrawing groups decrease the rate of the fluoro Pummerer reaction, which, in certain cases,7 allows a DAST-mediated deoxygenation to compete with the introduction of fluorine alpha to sulfur. The reaction is compatible with a number of functional groups and can readily be carried out with nucleosides. Robins and coworkers4 reported the synthesis of a 5 -fluoro-5 -S-phenyladenosine analog using antimony trichloride as catalyst at room temperature. It should be noted that a-fluoro sulfoxides provide a convenient entry to terminal fluoroalkenes.3 8 9 10... 

The procedure described here provides a stereospecific synthesis of (E)- and (Z)-fluoroalkenes from the corresponding (E)- and (Z)-fluorovinyl sulfones. Fluorovinyl sulfones obtained from ketones are, in most cases, readily separable into (E) and (Z) isomers either by crystallization or by chromatography.4 In the example described, only the (E)-fluorovinyl sulfone 1 is formed (which is converted into the (Z)-fluoroalkene 3 with complete retention of configuration). The reaction sequence has been used for the stereospecific synthesis of fluoroalkene nucleosides5 as well as for... 

J. R. McCarthy, D. P. Matthews, and J. P. Paolini 216 STEREOSELECTIVE SYNTHESIS OF 2,2-DISUBSTITUTED 1-FLUOROALKENES (E)-[[FLUORO-(2-PHENYLCYCLOHEXYLIDENE)-METHYL]SULFONYL]BENZENE AND (Z)-[2-(FLUOROMETHYLENE)-CYCLOHEXYL]BENZENE... 

Synthesis of funtionalized (Z)-fluoroalkene-type dipeptide isosteres (36) via Sml2-mediated reduction of y,y-difluoro-ot, -enoates 2.3.19. Reductive formation of fluoroolefins and subsequent conversion to diketopiperazine mimics (71). Nonpeptidic amide bond replacement... 

Otaka et al. reported the synthesis of (Z)-fluoroalkene dipeptide isosteres utilizing an organocopper-mediated reduction (Scheme 23) [69,70]. Reduction of 65 with Me2Cu(CN)Li2 2 LiBr-2 LiCI (4 equiv.) in THF-Et20 at -78°C for 15 min, proceeded unequivocally to yield the desired (Z)-fluoroalkene dipeptide isostere, eoc-Phei/r[(Z)-CF=CH]Gly-OEt (64) in 85% isolated yield. 

G. Dutheuil, X. Lei, X. Pannecoucke, J.C. Quirion, A novel diastereoselective synthesis of (Z)-fluoroalkenes via a Nozaki-Hiyama-Kishi-Type reaction, J. Org. Chem. 70 (2005) 1911-1914. 

A. Otaka, H. Watanabe, E. Mitsuyama, A. Yukimasa, H. Tamamura, N. Fujii, Synthesis of (Z)-fluoroalkene dipeptide isosteres utilizing organocopper-mediated reduction of y,y-difluoro-a,/ -enoates, Tetrahedron Lett. 42 (2001) 285-287. 

Y. Nakamura, M. Okada, A. Sato, H. Horikawa, M. Koura, A. Saito, T. Taguchi, Stereoselective synthesis of (Z)-fluoroalkenes directed to peptide isosteres Copper mediated reaction of trialkylaluminum with 4,4-difluoro-5-hydroxyallylic alcohol derivatives, Tetrahedron 61 (2005) 5741-5753. 

A. Niida, M. Mizumoto, T. Narumi, E, Inokuchi, S. Oishi, H. Ohno, A. Otaka, K. Kitaura, N. Fujii, Synthesis of (Z)-alkene and ( )-fluoroalkene-containing diketopiperazine mimetics utilizing organocopper-mediated reduction-alkylation and diastereoselectiv-ity examination using DFT calculations, J. Org. Chem. 71 (2006) 4118-4129. 

Even simple fluoroalkenes display exploitable electrophilic character. Bailey described an asymmetric synthesis of protected difluoroglycines initiated by nucleophilic addition/elimination at the difluorocentre of chlorotrifluoro-... 

Concerning the nature of the initiator no prediction can be made on the efficiency of such a reactant in the telomerisation of fluoroalkenes. Non fluorinated initiators led to unsuccessful results whereas investigations on the synthesis of highly fluorinated peresters or peroxides were performed by Rice and Sandberg [29] and Sawada [30], respectively. 

Perfluoroalkyl iodides have been used as telogens with most fluoroalkenes. An extensive kinetic research on the synthesis of monoadducts was performed by Tedder and Walton. From a review of the literature [97-99, 172, 236], the following reactivity scale may be proposed ... 

Fortunately, much work has still to be developed, and especially a better knowledge of the synthesis of tailor-made polymers with well-defined architecture in order to improve the properties by a better control of the regioselectivity and of the tacticity. Even if much work on the reactivity has been extensively carried out by Tedder and Walton, methods are searched for a better orientation of the sense of addition, since most fluoroalkenes are unsymmetrical. 

Table 3. Synthesis of Terminal Fluoroalkenes by Reaction of Vinyltin Compounds with F-Teda BF ...

Finally, an example of fluorination of the C = P bond has been reported." Reaction of the /1-oxido ylide 22 with gaseous perchloryl fluoride at — 35 C gives the fluoroalkenes 23A and B in 12 and 45 % yield, respectively. Alkene 23B is an intermediate in the synthesis of (-F)-13-fluoroprostaglandin methyl ester, a compound with antifertility and muscle-stimulating effects. 

This preference for fluoroalkenes to undergo [2 + 2] eycloaddition has resulted in the synthesis of a large number of fluorinated cyclobuianes. The reaction mechanism has been the subject of intense study. " ... 

There are four main general methods [40 2] for the preparation of perfluorinated alkenes, namely dehydrohalogenation, dehalogenation, pyrolysis and halogen exchange reactions of appropriate fluorinated precursors. The overall features of the mechanisms of each of these processes have already been discussed (Chapters 6 and 7, Sections 1 and 11). Representative examples of each of these types of synthesis are collated in Table 7.5 clearly the method of choice for the synthesis of a particular fluoroalkene will depend... 

Many of the synthetic approaches that are used for the preparation of fluoroalkenes can be adopted for the synthesis of polyfluorodienes. Examples of other processes such as reductive coupling methods and syntheses based on organometallic precursors [265] or phosphorous ylids are also included in Table 7.16. 

Pyrolysis of alkali-metal salts does not lead to simple decarboxylation but, instead, elimination of fluoride also occurs this is a useful S3mthetic method [36], commercialised in the synthesis of monomer for the manufacture of Nafion [37] (Figure 8.1) see Chapter 7, Section IIB for the preparation of fluoroalkenes. 

---