Perfluoroalkyl ketones

Acid hydrolysis of (i-perfluoroalkylvinylamines, prepared from secondary amines and perfluoroalkylacetylenes, yields p-aminovinyl perfluoroalkyl ketones as the major products [79] (equation 20)... 

A one-pot synthesis of alkyl perfluoroalkyl ketones has been developed. Phosphoranes, generated in situ, are acylated with a perfluoroacyl anhydnde, and the resultmg phosphonium salts are hydrolyzed with alkali [4S (equation 48) Hydrolysis of a carbon-sulfur bond in 2-chloro-2,4,4-trifluoro-1,3-dithietane-S-trioxide, which can be obtained from 2,2,4,4-tetrachloro-l,3-dithietane by fluor-mation with antimony trifluoride followed by selective oxidations, opens the nng to produce 2-chloro-1,1,2-trifluorodimethyl sulfone [49] (equation 49)... 

Lithium chlorodifluoroacetate in preparation of perfluoroolefins from perfluoroalkyl ketones, 48, 119... 

Germyl enol ethers react with perfluoroalkyl iodides under Et3B initiation to give a-pcrfluoroalkyl ketones. The intermediate radical adduct decomposes readily via /1-elimination and provides the a-perfluoroalkyl ketone and a trialkylgermanyl radical as a chain carrier (Scheme 12) [32]. 

Aubert, C. Rontani, J.-F. Perfluoroalkyl Ketones Novel Derivatization Products for the Sensitive Determination of Fatty Acids by Gas GC-MS in El and NICI... 

This assertion is borne out by the small deviations from fluid-isotropiclike values of the photoproduct ratios found in the Norrish II reactions of the two alkyl perfluoroalkyl ketones 76 (with m, n = 7,8 and 9,10) in the (macroscopically) highly ordered smectic phases of F10H10 [273,274]. As... 

Soloshonok and co-workers have developed a method for the synthesis of a-(perfluoro-alkyl)amines from perfluoroalkyl carbonyl compounds by a transamination involving an azomethine a/omethine (Schiffbase) isomerization. They call this method a biomimetic, base-catalyzed 1,3-proton shift reaction, and have applied it to perfluoroaldehydes,12-15 perfluoroalkyl ketones,12 18 / -(perfluoroalkyl)-/l-oxo esters,15 16 19 24 and - -( perfluoroalkyl)-a-oxo es-ters2 " -26 to synthesize the corresponding a-(perfluoroalkyl)amincs, / -(perfluoroalkyl )-/i-amino acids, and 3 -(perfluoroalkyl)- x-amino acids. 

A-Benzylimines 14 are readily prepared from perfluoroaldehydes or perfluoroalkyl ketones and benzylamine by refluxing in benzene or toluene in the presence of a catalytic amount of /)-toluenesulfonic acid, and with azeotropic removal of water.14 (Fluoroalkylidene)amines 14a-... 

Based on the results described above, the base-catalyzed 1,3-proton shift reaction constitutes a general approach to x-(perfluoroalkyl)amines 17 starting from perfluoroaldehydes and perfluoroalkyl ketones. 

Preparation of /V-Bcnzylimines 14 from Perfluoroaldehydes and Perfluoroalkyl Ketones General Procedure 14... 

The 1,3-proton shift reaction has also been applied to the synthesis of a-(perfluoroalkyl)-a-amino acids, specifically 3.3,3-trifluoroalanine.2 -26 Attempts to prepare the A-benzylimine of ethyl 3,3.3-trifluoro-2-oxopropanoate by direct condensation with benzylamine were very difficult due to the exceptionally high stability of the intermediate a-amino alcohol, which fails to dehydrate. By contrast, 1-phenylethanamine reacted with ethyl 3,3,3-trifluoro-2-oxo-propanoate to form ketimine 33 in 83 % yield.26 The 1,3-proton shift reaction of 33 is much faster than those of ketimines derived from perfluoroalkyl ketones or perfluoroaldehydes (see Table 5). Complete conversion in triethylamine required 6 hours at room temperature and afforded the isomeric Shiff base 34 in 92 % yield. Mild hydrolysis of Shifif base 34 gives a-amino ester 35, which in turn hydrolyzes to 3,3,3-trjfluoroalanine hydrochloride (36). 

Several methods for the synthesis of perfluoroalkyl ketones have taken advantage of the rate acceleration of a perfluoroalkyl group at position 2. Just as Krespan demonstrated the facile... 

Peptidyl fluoromethyl ketones are widely used as fairly potent inhibitors for a variety of proteases, including serine, cysteine, and aspartyl proteases. Unlike other halomethyl ketones (Section 15.1.3), fluoromethyl ketones are reversible transition-state mimics. The electron-withdrawing fluorine(s) next to the carbonyl group enhances the electrophilicity of the a-fluoroalkyl ketone functionality, thereby making the carbonyl more susceptible to nucleophilic attack. a-Fluoroalkyl ketones are good mimics of peptide bonds due to the small size of the fluorine and the stability of C F bonds. There are three general classes of peptidyl fluoromethyl ketones fluoromethyl ketones (irreversible inhibitors of cysteine proteases), difluoromethyl ketones (reversible inhibitors of both serine and aspartyl proteases), and trifluoromethyl/perfluoroalkyl ketones, which typically exist in hydrated forms and are excellent inhibitors of both serine and cysteine proteasesJ1 ... 

One of the most widely used methods for the synthesis of peptidyl fluoromethyl ketones is a modified Dakin-West acylation procedure. Although this reaction is primarily used for the synthesis of trifluoromethyl ketones (see Scheme 4), it is also frequently used to synthesize fluoroalkyl (Section 15.1.4.1.4), difluoroalkyl (Section 15.1.4.2.2), and perfluoroalkyl ketones. This method is extremely versatile however, there are several drawbacks. First, as noted in Section 15.1.4.1.2, several of the reagents used in the Dakin-West acylation are... 

Table 7 Examples of Perfluoroalkyl Ketones Synthesized by a Dakin-West Reaction12-81...

In this section the synthesis of fluoroalkyl (Section 15.1.4.1.3), a,a-difluoroalkyl (Section 15.1.4.2.3), and trifluoromethyl- and perfluoroalkyl ketones are discussed collectively. The second most widely used method for synthesizing peptide fluoromethyl ketones is the Henry nitro-aldol condensation reaction, which involves the use of (3-nitro alcohols to build the fluoromethyl ketones. As with the modified Dakin-West procedure, the Henry reaction has also been used to synthesize mono-, di-, tri-, and extended fluoromethyl ketones, making it another extremely versatile synthetic method.19 12 19 27 29 33 341 However, similar to the Dakin-West procedure, the products of the Henry reaction are not chiral, since an achiral carbanion is involved in the crucial carbon bond forming step. 

Perfluoroalkyl ketones have been reduced in high ee using a simple alkoxide lithium (S)-l-phenylethoxide, for example, reduces 2,2,2-trifluoroacetophenone to its (5>carbinol in 80% ee and 61% yield at 0°C, with acetophenone produced as by- ... 

Reduction of perfluoroalkyl ketones with chiral lithium alkoxides gave chiral a-perfluoroalkyl alcohols in high enantiomeric excesses. The order of steric effects on this reaction is estimated as C7F15 > substituted phenyl > CF3.388... 

FIGURE 1. Representative a-perfluoroalkyl ketones and 3 with their yields22... 

Aromatic aldehydes give the corresponding alcohols on reaction with trimethyl(polylluoroal-kyl)silanes in lelrahydrofuran in the presence of tetramcthylammoniuni fluoridc. The reaction of perfluoro-2-propoxypropanoyl fluoride with trimethyl(perfluoroalkyl)silane leads to the perfluoroalkylated ketone product. ... 

The fluoroform reaction has also been observed with higher perfluoroalkyl aldehydes and perfluoroalkyl ketones, which react with formation of l//-perfluoroalkanes and carboxylic acids. 

From a synthetic point of view, the synthesis of a-(perfluoroalkyl)ketones is preferably performed by the reaction of (perfluoroalkyl)phenyliodonium triflates with silyl enol ethers, which affords high yields of the perfluoroalkylated products (104) under mild conditions. The reaction of p,7 unsaturated silyl enol ethers with (perfluoroalkyl)phenyliodonium triflates led to the Y-perfluoroalkyl-a,p-unsaturated carbonyl derivatives (105) in good to high yields.212... 

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