Selective C-F bond

A versatile C4-building block, difluorinated Danishefsky s diene, was developed for the construction of fluorinated six-membered rings in the laboratory of K. Uneyama. The diene was prepared by the selective C-F bond cleavage of trifluoromethyl ketones. The reaction of this novel diene with benzaldehyde afforded the corresponding difluoro dihydropyrone in 92% ee in the presence of equimolar Ti(IV)-(R)-BINOL. ... 

Amii, H., Kobayashi, T., Hatamoto, Y. and Uneyama, K. (1999) Mg°-promoted selective C-F bond cleavage of trifluoromethyl ketones a convenient method for the synthesis of 2,2-difluoro enol silanes. J. Chem. Soc. Chem. Commun., 1323-1324... 

Silyl Enol Ethers. a,a-Difluorotrimethylsilyl enol ethers can be prepared through a Mg/TMSCl-promoted selective C-F bond cleavage of the corresponding trifluoromethyl ketones. An a,a-difluorinated analog of Danishefsky s diene was prepared in good... 

Fluorochloro, fluorobromo, and fluoroiodoalkanes react selectively with aromatics under boron trifluoride catalysis to provide chloro-, bromo- and iodoalkylated products (48). The higher reactivity of the C—F bond over C—Cl, C—Br, and C—I bonds under Lewis acid catalysis results in the observed products. 

Thus when the degree of fluorination increased, the selectivity for the fluorination reaction decreased. The dehydrofluorination reaction required the rupture of the C-F bond of the CF3CH2CI molecule while the fluorination reaction involved the rupture of the C-Cl bond. The C-F bond being harder to split than the C-Cl bond [11], the dehydrofluorination reaction require stronger adsorption sites than the fluorination reaction. 

The bond dissociation energy of fluoromethane is 115 kcal mol , which is much higher than the other halides (C-Cl, C-Br and C-1, respectively 84, 72 and 58 kcal mol ) [6], Due to its strength, the carbon-fluorine (C-F) bond is one of the most challenging bonds to activate [7], A variety of C-F bond activation reactions have been carried out with different organometallic complexes [8], Among them, nickel [9] and ruthenium complexes have proven to proceed selectively under mild conditions [10],... 

In contrast, selective inhibition of enzyme activity involves highly specific interactions between the protein and chemical groups on the xenobiotic. An excellent example of this type of inhibition is seen in the toxic effect of fluoroacetate, which is used as a rodenticide. Although fluoroacetate is not directly toxic, it is metabolized to fluoroacetyl-CoA, which enters the citric acid cycle due to its structural similarity to acetyl-CoA (Scheme 3.5). Within the cycle, fluoroacetyl-CoA combines with oxalo-acetate to form fluorocitrate, which inhibits the next enzyme, aconitase, in the cycle [42]. The enzyme is unable to catalyze the dehydration to cis-aconitate, as a consequence of the stronger C-F bond compared with the C-H bond. Therefore, fluorocitrate acts as a pseudosubstrate, which blocks the citric acid cycle and, subsequently, impairs ATP synthesis. 

Electrooptical properties will be covered only briefly. Fluorocarbons find widespread utility in altering electrooptical properties of coatings. These properties are to be considered as derived from bulk properties of the fluorocarbon. In that regard, fluoropolymers are the most often selected. It is known from Eq. (2) that the electrooptical properties of fluorocarbons can be linked directly to the nature of the C—F bond (a oc n and e <=< n ). It is instructive to consider some relevant values. The dielectric constants e of PTFE, PE, and nylon-6,6 have been determined to be 2.1 (60 Hz-2 GHz), 2.2-2.3 (1 kHz), and 3.6-3.0 (100 Hz-1 GHz), respectively. The dielectric constants for PE and PTFE are comparable. The explanation can be found by comparing segmental polarizabilities a for groups with C—F bonds versus those with C—H bonds, as shown in Table 4.1. They are nearly identical. As e is related to a, it is not surprising that PE and PTFE have similar dielectric constants. The value of e for nylon-6,6 is included above for comparison. 

In the similar structure of l.l,1,2,4,4,4-heptafluoro-3-phenylbut-2-ene, the reduction with sodium borohydride takes place readily under mild conditions and both products of vinylic and allylic Sn2 displacement are obtained the relative amounts of the products can be controlled by adding triphenylphosphane to the mixture80 (Table 2). The nonfluorinated chain in Hpenta-fluorophenyl)-2-phenylethane (12) selectively activates the para C-F bond to reduction by lithium aluminum hydride, giving the monoreduced product 13 in high yield.81... 

Selective reduction of only one C-F bond in hexafluoroacetone (1) to give enol 2 is accomplished using activated aluminum as a reducing agent.89 90 It has been found in the reduction of hexafluoroacetone by magnesium metal in tetrahydrofuran that the intermediate penta-fluoropropen-2-olate subsequently reacts with a molecule of hexafluoroacetone to yield per-... 

In aryl alkyl ketones, there are two types of C-F bonds to reduce. Fluorine atoms in the a-positions are usually more easily replaced than those on the aromatic ring. It is also possible to reduce a-C-F bonds selectively without affecting the carbonyl group. 

Selective polarographic reduction of a-C-F bonds in 2,2,2-trifluoro-l-phenylethanone is performed under high pH, while in acidic media the compound is reduced without loss of fluorine to the alcohol and the corresponding pinacol.98 l,2-Dimethyl-2-phenylbenzimidazole, which is a novel and efficient reducing agent, transforms 2,2,2-trifluoro-l-phenylethanone(8) effectively into acetophenone with high yield.99... 

A very rare example of preferential photochemical reduction of an a-C-F bond rather than a //-chlorine occurs with chlorofluoropropanoates, in which this unusual selection in radical reactions is achieved by photochemical reduction.107 In oc.oc-difluoro esters 6 both C-F bonds can be reduced stepwise using hexamethylphosphoric triamide as the solvent and hydrogen donor.108 100... 

Three types of C-F bonds are encountered in unsaturated acids and their functional derivatives, namely nonactivated aliphatic, activated aliphatic (allylic, benzylic, and a to carbonyl), and vinylic bonds. The ease and selectivity of the reduction of C-F bonds is strongly dependent on the chemical environment. 

In AC(2-ehloroethyl)-2-fluoroaeetamide (4) both the activated C-F bond and carbonyl group are selectively reduced with a mixture of lithium aluminum hydride and aluminum(Ill) chloride, while the chlorine in an unactivated position remains unaffected, affording 5.129... 

Mattay et al., having discovered exciplex emission from solutions of benzene and 1,3-dioxole [122], continued their investigations with a study on selectivity and charge transfer in photoreactions of a,a,a-trifluorotoluene with 1,3-dioxole and some of its derivatives, and with vinylene carbonate and dimethylvinylene carbonate [15,143,144], a,a,a-Trifluorotoluene and 1,3-dioxole upon irradiation yield three types of products ortho cycloadducts, meta cycloadducts, and so-called substitution products (Scheme 44). The products are formed in the ratio ortho adductsimeta adducts substitution products = 0.8 1.7 0.3. The substitution reaction (which is really an addition of a C—F bond to the double bond of 1,3-dioxole, but named substitution in order to distinguish it from the ortho addition [186] is supposed to start with electron transfer from 1,3-dioxole to excited a,a,a-trifluorotoluene. The radical anion then releases a fluoride ion, which adds to the 1,3-dioxole radical cation. Radical combination then leads to the product. 

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