Fluorinated ketones, effect

Most peptidyl a,a-difluoroalkyl ketones are actually extended chains based on statone, rather than simple difluoromethyl ketones. The statone derivatives are based on pepstatin, which is an extremely potent peptide inhibitor of aspartic proteases. The difluoro derivatives of statone take advantage of both the electronegativity of fluorine and the potential for additional interactions between the protease and structures on the leaving group side of the inhibitor. 15 This dual nature is part of what makes a,a-difluoroalkyl ketones effective inhibitors of aspartyl proteases as well as serine proteases. There are three main methods of synthesizing peptidyl a,a-difluoroalkyl ketones (1) the Reformatsky reaction with peptide aldehydes (Section 15.1.4.2.1), (2) a modified Dakin-West reaction (Section 15.1.4.2.2), and (3) a Henry nitro-aldol condensation (Section 15.1.4.2.3). 

The Tr values of the two fluorinated ketones are much longer than those of their protonated counterparts. The origin of this effect is not clear at this time. Successive chlorination of halogenated acetones appears to lengthen tr somewhat tr values of 1.7 ps for CIF2COCF3, -2.0 ps for CIF2COCIF2, and 3.0 ps for CIF2COCI2F have been reported (94). 

Fluorinated ketones are important because of their versatile reactivity. HFA, the simplest perfluorinated ketone, reacts readily with nucleophiles as a result of the electron-withdrawing effect of the triflnoromethyl groups. A wide range of both hnear and cychc heteroatom adducts are accessible, as shown in Scheme 4. ... 

Alcock and Whittle had previously reported on a similar reaction involving CF3 and CH3 radicals, but Pritchard and Bryant ° > ° showed that the related reaction between CF2H radicals was of little importance during the photolysis of 1,1,3,3-tetrafluoroacetone. Robb et alP have discussed the cage effect in the liquid-phase photolysis of fluorinated ketones. 

A synthesis of cross-conjugated 2-cyclopenten-l-ones from dialkenyl ketones is readily induced by TMSOTf (eq 73). A strong fluorine-directing effect has been observed for such Nazarov-type cycUzation, as mixtures of products have been observed for nonfluorinated dialkenyl ketones. The addition of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as a cosolvent dramatically accelerates the cyclization. Other acids such as BF3-OEt2, FeCls, polyphosphoric acid, or TiOH are less effective while neither TMSI nor TMSOMe promote this cyclization at all in CH2CI2. 3-Ethoxycarbonyltetrahydro-)/-pyrones also undergo such Nazarov-type cyclization. ... 

As mentioned in Section 10.2.3, the application of Ga(OTf)3 as an effective and reusable catalyst for the Strecker reaction has been demonstrated [62]. This is a simple and alternative route to the stepwise methodologies for the Strecker reaction of ketones. Moreover, the use of fluorinated ketones is a significant aspect of this procedure due to the increase interest in organofluorated compounds. 

The stereodirecting effect of the iron complex can also be exploited for diastereo-selective fluorination and oxygenation of adjacent silyl enol ethers (Scheme 4-95). Transformation of the allyliron complex into the diene complex and subsequent removal of the complex moiety by oxidation with ceric ammonium nitrate provide the enantiopure a-hydroxylated or fluorinated ketone, respectively. ... 

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). 

Fluorinated Acids. This class of compounds is characterized by the strength of the fluorocarbon acids, eg, CF COOH, approaching that of mineral acids. This property results from the strong inductive effect of fluorine and is markedly less when the fluorocarbon group is moved away from the carbonyl group. Generally, their reactions are similar to organic acids and they find apphcations, particularly trifluoroacetic acid [76-05-1] and its anhydride [407-25-0] as promotors in the preparation of esters and ketones and in nitration reactions. 

Chemical Properties. A combination of excellent chemical and mechanical properties at elevated temperatures result in high performance service in the chemical processing industry. Teflon PEA resins have been exposed to a variety of organic and inorganic compounds commonly encountered in chemical service (26). They are not attacked by inorganic acids, bases, halogens, metal salt solutions, organic acids, and anhydrides. Aromatic and ahphatic hydrocarbons, alcohols, aldehydes, ketones, ethers, amines, esters, chlorinated compounds, and other polymer solvents have Httle effect. However, like other perfluorinated polymers,they react with alkah metals and elemental fluorine. 

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],... 

The cationic Pd(II) catalysts exhibit effective copolymerizations of ethylene and other a-olefins with polar-functionalized comonomers, with the majority of insertions occurring at the ends of branches. Among the best tolerated monomers are those bearing fluorine or oxygen-containing functionalities, such as esters, ketones, and ethers. The copolymerization of ethylene and acrylates, attractive because the monomers are inexpensive and the copolymers exhibit unique physical properties, has been well-studied mechanistically [27,69], Examples of copolymerizations of ethylene and a-olefins with methyl acrylate are shown in Table 4. In general, the amount of comonomer incorporation varies linearly with its reaction concentration and... 

Crystallinity of these hexafluoroisopropylidene-unit-containing poly(ketone)s is low except for poly(sulfide ketone) (13). The water contact angle for the fluorine-containing poly(ketone) films is high, being 98° for poly(ether ketone) (11), from 2,2-bis(4-carboxyphenyl)-l,l, l,3,3,3-hexafluoropropane(15) and 96° for poly(sulfide ketone) (13) from 15, whereas it is 78° for poly(ether ketone) from 2,2-bis(4-carboxy-phenyl)propane (16) and 74° for the poly(sulfide ketone) from 16. This result indicates that the substitution of isopropylidene units of poly-(ketone)s with hexafluoroisopropylidene units has a remarkable effect on the surface properties of poly(ketone) films. 

Cyclohexane is more environmentally acceptable than the more commonly-used CCl. A recent cleavage of a mono-fluorinated alkene to a ketone was thus effected. The alkene (70 mg, 0.28 mmol) was dissolved in a mixture of acetonitrile (0.5 cm ) and cyclohexane (0.5 cm ) and treated with RuClj.nH O (0.05 g, 0.2 mmol) and Na(lO ) (0.24 g, 10 mmol) in water (1 cm ). The mixture was stirred for 1.5 h, the product extracted with diethylether and dried over MgSO [330]. Other examples, using RuCyaq. 10(0H)j/CgHj2-CH3CN have been given [216]. 

The most general and useful application of sulfur tetrafluoride is replacement of carbonyl oxygen and hydroxy groups by fluorine. The reaction has broad scope and is effective with all carbonyl and hydroxy compounds. Alcohols are converted into monofluoro derivatives 1, aldehydes, ketones and quinones into gew-difluoro compounds 2 and 3, and carboxylic acids, acid anhydrides, acid halides and amides into trifluoromethyl compounds 4. 

Direct regioselective conversion of a variety of cyclic and acyclic ketones to a-fluoro ketones was achieved in high to excellent yield using NFTh (21) in acetonitrile solution.96 The collected results (Table 10) of this highly effective direct transformation show that a comprehensive range of ketones can be fluorinated a to the carbonyl group, without prior activation. 

---