Fluorinated ketones, hydrogenation

X0 esters in the 2-position, but is not sufficiently reactive to fluorinate ketones. jl-Oxo esters are selectively fluorinated at the a-position by iodotoluene difluoride and a hydrogen fluoride pyridine complex. " ... 

The charge-potential model was used to predict the chemical shifts for functional groups in a number of model compounds containing primarily carbon, fluorine, and hydrogen. The molecular structure examined included aliphatics, olefins, aromatics, and several ketones. 

Sulfur tetrafluoride [7783-60-0] SF, replaces halogen in haloalkanes, haloalkenes, and aryl chlorides, but is only effective (even at elevated temperatures) in the presence of a Lewis acid catalyst. The reagent is most often used in the replacement of carbonyl oxygen with fluorine (15,16). Aldehydes and ketones react readily, particularly if no alpha-hydrogen atoms are present (eg, benzal fluoride [455-31-2] from benzaldehyde), but acids, esters, acid chlorides, and anhydrides are very sluggish. However, these reactions can be catalyzed by Lewis acids (HP, BF, etc). 

Selective fluonnation in polar solvents has proved commercially successful in the synthesis of 5 fluorouracil and its pyrimidine relatives, an extensive subject that will be discussed in another section Selective fluonnation of enolates [47], enols [48], and silyl enol ethers [49] resulted in preparation of a/phn-fluoro ketones, fieto-diketones, heta-ketoesters, and aldehydes The reactions of fluorine with these functionalities is most probably an addition to the ene followed by elimination of fluonde ion or hydrogen fluoride rather than a simple substitution In a similar vein, selective fluonnation of pyridmes to give 2-fluoropyridines was shown to proceed through pyridine difluondes [50]... 

Mixtures of anhydrous hydrogen fluoride and tetrahydrofuran are successfully used as fluorinating agents to convert 1,1,2-trifluoro-l-allcen-3-ols, easily prepared from bromotrifluoroethene via lithiation followed by the reaction with aldehydes or ketones, to 1,1,1,2-tetrafluoro-2-alkenes The yields are optimal with a 5 1 ratio of hydrogen fluoride to tetrahydrofuran The fluorination reaction involves a fluonde lon-induced rearrangement (Sf,j2 mechanism) of allylic alcohols [65] (equation 40)... 

Rearrangement of fluorine with concomitant ring opening takes place in fluorinated epoxides Hexafluoroacetone can be prepared easily from perfluo-ropropylene oxide by isomerization with a fluorinated catalyst like alumina pre treated with hydrogen fluoride [26, 27, 28] In ring-opening reactions of epoxides, the distribution of products, ketone versus acyl fluoride, depends on the catalyst [29] (equation 7) When cesium, potassium, or silver fluoride are used as catalysts, dimenc products also are formed [29]... 

Table 2 Results of the transfer hydrogenation of ketones with fluorinated (salen)Ir complexes under biphasic conditions ...

Table 3 summarizes the scope and limitation of substrates for this hydrogenation. Complex 5 acts as a highly effective catalyst for functionalized olefins with unprotected amines (the order of activity tertiary > secondary primary), ethers, esters, fluorinated aryl groups, and others [27, 30]. However, in contrast to the reduction of a,p-unsaturated esters decomposition of 5 was observed when a,p-unsaturated ketones (e.g., trans-chalcone, trans-4-hexen-3-one, tra s-4-phenyl-3-buten-2-one, 2-cyclohexanone, carvone) were used (Fig. 3) [30],... 

Besides the above-mentioned catalytic asymmetric hydrogenation method for preparing fluorine-containing compounds, other reactions such as asymmetric reduction of achiral fluorine-containing ketones are also feasible methods for preparing chiral fluorinated compounds. For example, the oxazabor-olidine system, which has been discussed in Chapter 6, can also be employed in the catalytic reduction of trifluoromethyl ketones. Scheme 8 40 depicts some examples.85... 

Fluorine at the equatorial 6a position also results in an increase in potency. One scheme for the production of such a compound relies on the shift of the double bond from the 4,5 to the 5,6 position, which follows the formation of an acetal at position 3. The scheme starts with the selective reduction of the 11 ketone in the cortisone intermediate (13-2). Epoxidation of the product (18-1) with a peracid takes place selectively at the unconjugated double bond to give the 5a,6a oxirane (18-2). Treatment of that with hydrogen fluoride in tetrahydrofuran leads to fluorohydrin (18-3). (There is evidence to indicate that the reagent involves an HF THF acid base complex since the omission of THF in at least some cases leads to a complex mixture of rearrangement products [15].) The side chain in fluorohydrin (18-3) is then converted... 

Formal replacement of hydrogen by fluorine takes place in the a-position of a ketone by treatment of enol acetates with triethylamine tris(hydrogen fluoride).51-55 The kinetically favored isomers are formed.51,55 Furthermore, benzylic positions bonded with an electron-withdrawing group (ketone, ester, nitrile, sulfonate) can be fluorinated electrochemically.51" 6-58 There are also various examples of the preparation of a-fluorosulfides front sulfides.51... 

Diazoalkanes, diazoketones, and diazoacetates can be fluorinated at 0 C with the loss of nitrogen by treatment with 70 % hydrogen fluoride/pyridine (a,a-hydrofluorinations) in 30-95 % yield.31 133 Furthermore, diazo ketones and diazoacetates when N-halosuccinimide is additionally introduced into the hydrogen fluoride medium.133... 

Aliphatic ketones without any os-hydrogen atoms react smoothly with sulfur tetrafluoride, but usually vigorous reaction conditions are required. Thus, 2,2,4,4-tetramethylcyclobutane-l,3-dione is remarkably resistant towards sulfur tetrafluoride the fluorination takes place at 160 C without charring to give a 73% yield of l,l,3,3-tetrafluoro-2,2,4,4-tetramethylcyclobutane (20).96... 

The methyl and trifluoromethyl radicals formed in the photolysis are assumed to abstract hydrogen, but not fluorine, atoms from the parent ketone. 

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