Aldehydes fluorination

Aldehydes. Fluorinated aldehydes are unknown. It has been observed that the reduction of a fluoro acid yields the alcohol directly, and also that the oxidation of a fluoro alcohol does not stop short of the acid.88... 

The limitations of this reagent are several. It caimot be used to replace a single unactivated halogen atom with the exception of the chloromethyl ether (eq. 5) to form difluoromethyl fluoromethyl ether [461 -63-2]. It also caimot be used to replace a halogen attached to a carbon—carbon double bond. Fluorination of functional group compounds, eg, esters, sulfides, ketones, acids, and aldehydes, produces decomposition products caused by scission of the carbon chains. 

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). 

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. 

Torlon-type polymers are unaffected by aliphatic, aromatic, chlorinated and fluorinated hydrocarbons, dilute acids, aldehydes, ketones, ethers and esters. Resistance to alkalis is poor. They have excellent resistance to radiation. If a total of 10 Mrad is absorbed at a radiation dosage of 1 Mrad/h the tensile strength decreases by only 5%. 

The recent discovery of a convenient synthesis of sulfur tetrafluoride from sulfur dichloride and sodium fluoride in acetonitrile invited the application of this reagent in fluorination reactions. Hasek, Smith and Engelhardt showed that carboxylic acids and their derivatives can be converted into trifluoromethyl derivatives and that aldehydes and ketones are converted into 5 em-difluoro compounds. They also observed that the reaction was acid... 

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]... 

Trimelhylsilyl enol ethers are effective substrates in fluorination with fluo-roxytrifluoromethanefor the preparation of a-fluoro esters, amides and aldehydes [J7] (equations 13-15)... 

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)... 

A fluorine-hydrogen migration is typical for the reactions of aldehydes branched at the carbon atom a to the formyl group. Comparable amounts of 1,1 -difluoroalkanes and 1,2-difluoroalkanes together with bis(l -fluoroalkyl) ethers are obtained [169] (equation 84). 

Because aldehydes react with aminofluorosulfuranes more readily than ketones, keto aldehydes can be selectively fluorinated at the formyl group [94, 183] Haloacetaldehydes react with DAST to give bis(l-fluorohaloethyl) ethers as the only or main products [170] (equation 96)... 

Replacement of hydrogen with halogen can be carried out in the alpha position of fluorinated ethers, amines, aldehydes, or nitriles In 2,2,3,4,4,4 hexafluoro-bulyl methyl ether, chlorination occurs predominantly at the methyl, however, bromination occurs mostly at the internal position of the fluorobutyl group 133] (equation 20)... 

A fluorinated oxazine, prepared fromfluoroacetonitrile and 2 methyl-1,3-pen-tanediol, is alkylated at low temperature The resulting products furnish a fluoro aldehydes after botohydride reduction and hydrolysis [JJ4] (equation 99)... 

In contrast, fluorinated ketones have been used as both nucleophilic and electrophilic reaction constituents The (Z)-lithium enolate of 1 fluoro 3,3-di-methylbutanone can be selectively prepared and undergoes highly diastereoselec-tive aldol condensations with aldehydes [7] (equation 8) (Table 4)... 

Table 6. Aldol Reaction of Fluorinated Enol Phosphates with Aldehydes [14 ...

Fluonnated aldehydes, where the fluorine is located a to the carbonyl [40] or more remotely, undergo olefination reactions cleanly [41, 42, 43] (equation 32) (Table 11)... 

Table 11. a-and (3-Fluorinated a, 3-Unsaturated Aldehydes in Olefination Reactions [43 ... 

Hexafluoroacetone and certain perfluorinated or partially fluorinated ketones, aldehydes, and imines react with a-functionalized carboxylic acids (e.g., a-amino, a-At-methylamino [S3, 84], a-hydroxy [S5], and a-mercapto [Sd] acids) to give five-membered heterocyclic systems (equation 13). 

Acetylene works Acrylates works Aldehyde works Aluminum works Amines works Ammonia works Anhydride works Arsenic works Asbestos works Benzene works Beryllium works Bisulfate works Bromine works Cadmium works Carbon disulfide works Carbonyl works Caustic soda works Cement works Ceramic works Chemical fertilizer works Chlorine works Chromium works Copper works Di-isocyanate works Electricity works Fiber works Fluorine works Gas liquor works Gas and coke works Hydrochloric acid works Hydrofluoric acid works Hydrogen cyanide works Incineration works Iron works and steel works... 

Figure 8.27 Reduction of aldehyde in SCCO2 by an isolated enzyme, horse liver alcohol dehydrogenase (HLADH) [20c] (a) Reaction scheme (b) fluorinated coenzyme soluble in CO2 and (c) effect of coenzyme on the reaction.

Rovis and co-workers have also extended the intermolecular Stetter reaction to inclnde nitroaUcenes as the electrophilic component. Fluorinated triazolinm precatalyst 155 was effective in catalysing the reaction of a variety of heteroaromatic aldehydes 153 with nitroalkenes 154 to generate P-nitroketones in excellent yields and enantioselectivities. The authors propose that stereoelectronically induced conformational effects on the catalyst skeleton are key to the high selectivities observed with flnorinated catalyst 155 (Scheme 12.33) [69],... 

The best carbonyl components for these reactions are highly electrophilic compounds such as glyocylate, pyruvate, and oxomalonate esters, as well as chlorinated and fluorinated aldehydes. Most synthetic applications of the carbonyl-ene reaction utilize Lewis acids. Although such reactions may be stepwise in character, the stereochemical outcome is often consistent with a cyclic TS. It was found, for example, that steric effects of trimethylsilyl groups provide a strong stereochemical influence.28... 

The kinetics of deuterium isotope exchange between diphenyl phosphine and t-butylthiol have been studied by H n.m.r. spectroscopy.274 A negative temperature coefficient was observed for the reaction of a perf1uoroalky1 phosphite with a fluorinated aldehyde.275 The kinetics for the reaction of alcohols with phosphoryl trichloride bore strong similarities to those of carboxylic acid derivatives.276 An interesting report desribed the solvolysis of ary 1 hydroxymethyl-phosphonates. It was shown that a phosphoryl group does not prevent carbocation formation on an immediately adjacent carbon atom.277... 

Dialkylaminosulfur trifluorides are widely used as a safe substitute for SF4 in the replacement of oxygen by fluorine in many types of organic compounds, for example, converting alcohols to fluorides, or aldehydes and ketones to gem-difluorides. The most familiar of these reagents is DAST, while an increasingly popular one (considered safer to use than DAST) is bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor Reagent) (Scheme 7.15). 

The heterobimetallic asymmetric catalyst, Sm-Li-(/ )-BINOL, catalyzes the nitro-aldol reaction of ot,ot-difluoroaldehydes with nitromethane in a good enantioselective manner, as shown in Eq. 3.78. In general, catalytic asymmetric syntheses of fluorine containing compounds have been rather difficult. The S configuration of the nitro-aldol adduct of Eq. 3.78 shows that the nitronate reacts preferentially on the Si face of aldehydes in the presence of (R)-LLB. In general, (R)-LLB causes attack on the Re face. Thus, enantiotopic face selection for a,a-difluoroaldehydes is opposite to that for nonfluorinated aldehydes. The stereoselectivity for a,a-difluoroaldehydes is identical to that of (3-alkoxyaldehydes, as shown in Scheme 3.19, suggesting that the fluorine atoms at the a-position have a great influence on enantioface selection. 

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