4.4- Disubstituted fluorine-containing

Utilization of UNs with fluoroalkyl substituents 201 makes possible the synthesis of 4,4-disubstituted fluorine-containing pyrans 202 (02JFC63) (Scheme 75). Phospho- and fluoro-containing pyranopyrazoles 203 were obtained similarly (04JFC1853) (Scheme 75). 

Hydrogenated isoxazole derivatives were obtained by single electron transfer (SET) cyclization of /9,y-unsaturated oximes , by thermal [4- -2] cycloaddition of aldox-imes or ketoximes to conventional dienophiles or isomerization/cyclization of an ortho halogeno or nitro-substituted amidoximes. Preparation of 1,4-disubstituted 3-hydroximino-2-nitro-l-butenes and their oxidative cyclization to 4-nitroisoxazoles are reported " . Synthesis of fluorine-containing substituted isoxazolidines as well as isoxazoles by ultrasonic methods has been also described. 

With some exceptions, 1,2-disubstituted ethylenes containing substituents larger than fluorine such as maleic anhydride, stilbene, and 1,2-dichloroethylene exhibit little or no tendency... 

The LLB type catalysts were also successfully applied in the asymmetric nitroaldol reaction of the quite um-eactive a,a-difluoro aldehydes. In general, catalytic asymmetric syntheses of fluorine-containing compounds are rather difficult [32]. However, catalytic asymmetric nitroaldol reaction of a broad variety of a,a-difluoro aldehydes 20,22,24,26,28, and 30 proceeded satisfactorily when using the heterobimetallic asymmetric catalysts with modified, 6,6 -disubstitut-ed BINOL ligands [33] (Scheme 7). The best results were obtained with the sa-marium(III) complex (5mol%) generated from 6, 6 -bis (triethylsilyl)ethy-nyl BINOL with enantioselectivities up to 95% ee. 

Li P, Chai Z, Zhao G, Zhu S-Z (2008) Synthesis of 3-fluoro-2,5-disubstituted furans and further derivative reactions to access fluorine-containing 3,3 -bifurans and tetrasubstituted furans. Synlett 2547-2551... 

Disubstituted alkenes react with 1-chloro- and l-bromo-2-trifluoroacetylacetylenes even at 20°C. However, the 1,2-substituted alkenes need heating at 70-80°C. Tarring does not occur and the reaction leads to a mixture of cyclobutene (A) and a product of ene reaction (B) (Scheme 4.8 and Table 4.1). The ene-adducts readily add bromine to the nonconjugated double bond, while cyclobutenes react slowly even at 0°C. The bromination allows the cyclobutenes to be separated by distillation. So, this approach made accessible a class of fluorine-containing cyclobutenyl ketones for use as intermediates in organic synthesis. 

Aryl fluoroalkyl ethers have been prepared from the reaction, at room temperature in HMPA, of fluo-ro-substituted alkoxides with activated fluoro-,149 nitro-,149 and, at 150 °C, also chloro-arenes150,151 and some chloro-substituted pyrazines (equation 15), pyrimidines, quinolines,150,152 and pyridines.152 Disubstitution was observed in die presence of comparably activated leaving groups such as in 2,4- and 2,6-di-chloronitro- or cyano-benzenes, whereas regiospecific substitution took place at position 4 in 3,4-dichloronitro- or cyano-benzene and at position 2 in 2-fluoro-6-chlorocyanobenzene.151 Steric hindrance and the number of fluorine substituents in the alkoxide pose limits to the reactivity. Thus, tertiary alkoxides, or alkoxides containing more than four fluorine substituents, displace activated nitro and fluoro, but not chloro substituents.149,150 The secondary hexafluoro-2-propoxide anion does not react even with the more reactive nitro and fluoro derivatives.149... 

Direct anodic fluorination of 1,2-disubstituted pyrroles 14 gives 5-fluoropyrroles 16 and/or fluorinated adducts 15,17, pyrroUn-2-ones 18. The transformation is performed with platinum plate electrode in acetonitrile containing supporting fluoride salts EtsN-nHF [12]. The structure of product depends on supporting fluoride salts. 

Few examples are reported in the literature regarding the reactivity of fluorinated 1,2,5-oxadiazoles. As for many azoles, the nucleophilic substimtion of a fluorine atom is relatively easy and provided high yields. Huorofurazans A react with bisfuraza-nopyrazine dianion 194 yielding a disubstituted compound 195 (73 %) containing two tris (furazanyl)-amino moieties [98], The same reaction performed on fluoro-derivative B gave compound 196 (85 %), the precursor of macrocycle 197 synthesised by oxidative cyclization with dibromoisocyanurate (DBI) (Scheme 50). 

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