Alcohols trifluoromethyl

For many years now, the reactivity of trifluoromethyl bromide has been underestimated. During the past decade the major breakthrough in this area has been the realisation that trifluoromethylation of organic compounds with this halide can be induced by mild reductants such as thiolates, zinc or sulfoxylate radical anion. Nowadays, a great variety of fluorinated products are available by these new methods sodium triflinate and triflic acid, trifluoromethylated alcohols, trifluoromethyl-containing aromatic compounds, ethyl trifluoropyruvate, trifluoromethylsulfides. ... 

Carbonyl reduction. Many substrates have been reduced enantioselectively to give alcohols trifluoromethyl ketones, a-acetoxyketones, pyridinophenones, ethyl a-methylacetoacetate, a-keto acid derivatives," and 3-chloro-2-oxoaIkanoic esters a,/3-Epoxy ketones undergo reduction and hydrolytic ring opening/... 

FLUORINECOMPOUNDS,ORGANIC - FLUORINATED AROMATICCOMPOUNDS] (Volll) p-Fluoro-a,a-bis(trifluoromethyl)benzyl alcohol [2402-74-6]... 

Synthetic applications of organosulfur reagents are expanding rapidly. Stable sulfuranes are included for the first time in BIS[2,-2,2-TRIPLUORO-l-PHENYL-l-(TRIFLUOROMETHYL)ETHOXY] diphenyl SULFURANE and DIETHYLAMINOSULFUR TRI-FLUORIDE. The latter is used to transform an alcohol to a fluoride in p-NITROBENZYL FLUORIDE. The direct homologation of a ketone to a nitrile by use of p-TOLYLSULFONYLMETHYL ISOCYANIDE is illustrated in 2-ADAMANTANECARBONITRILE. Reagents with... 

A vanety of secondary alcohols with terminal trifluoromethyl group are oxidized by the Dess-Martin periodinane reagent [52 57] (equation 48)... 

Trifluoromethyl-l-phenylethyl tosylate has been used to differentiate as shown in Table 1, the solvolytic power of three fluorinated solvents and to compare these with formic and acetic acids The three fluorinated solvents are trifluoroacetic acid, trifluoroethanol, and 1,1,1,3,3,3-hexafluoroisopropyl alcohol [55]... 

Electrochemically generated trifluoromethyl radicals add to 1-hexyne to give a 1 4 mixture of ( )- and (Z)-l,l,l-trifluoro-2-heptene [22] Kinetic data on the addition of photochemically generated trifluoromethyl radicals to acetylene and substituted acetylenes were reported [2J]. Alcohols and aldehydes add to hexa-fluoro-2-butyne in the presence of peroxide and y-ray initiation [24] (equations 16 and 17). 

Novel fluonnated 2,2-bis(trifluoromethyl)dioxolanes containing alkyne groups [97] have been synthesized from hexafluoroacetone and either 1,4-dibro-mo-2-butene-orpropargylic alcohol [92]. 

A solution of 1.0 gram of 10-[3 -(N-acetoxyethylpiperazinyl)-propyl]-2-trifluoromethyl-phenothiazine in 25 ml of 1 N hydrochloric acid is heated at reflux briefly. Neutralization with dilute sodium carbonate solution and extraction with benzene gives the oily base, 10-[3 -(N-(3-hydroxyethylpiperazinyl)-propyl]-2-trifluoromethylphenothiazine. The base is reacted with an excess of an alcoholic hydrogen chloride solution. Trituration with ether separates crystals of the dihydrochloride salt, MP 224° to 226°C, (from U.S. Patent 3,058,979). 

Lipase-catalyzed methanolysis of racemic N-benzyloxycarbonyl (Cbz) amino acid trifluoroethyl esters carrying aliphatic side chains afforded the L-methyl esters and the D-trifluoromethyl esters (Figure 6.16). The released alcohol (CF3CH2OH) is a weak nucleophile that cannot attack the ester product. The nucleophilidty of the leaving group is depleted by the presence of an electron-withdrawing group [63]. 

Nucleophilic attack of alcohols (e.g., ethanol) on a-lactones gives different regiochemistry depending on the snbstitnent R. In cases where R is alkyl or phenyl, ethanol reacts with a-lactones to prodnce a-ethoxyacids 3, presnmably via zwit-terionic form When R is the strongly electron-withdrawing trifluoromethyl... 

Arguably the most challenging aspect for the preparation of 1 was construction of the unsymmetrically substituted sec-sec chiral bis(trifluoromethyl)benzylic ether functionality with careful control of the relative and absolute stereochemistry [21], The original chemistry route to ether intermediate 18 involved an unselective etherification of chiral alcohol 10 with racemic imidate 17 and separation of a nearly 1 1 mixture of diastereomers, as shown in Scheme 7.3. Carbon-oxygen single bond forming reactions leading directly to chiral acyclic sec-sec ethers are particularly rare since known reactions are typically nonstereospecific. While notable exceptions have surfaced [22], each method provides ethers with particular substitution patterns which are not broadly applicable. 

The indium-mediated allylation of trifluoroacetaldehyde hydrate (R = H) or trifluoroacetaldehyde ethyl hemiacetal (R = Et) with an allyl bromide in water yielded a-trifluoromethylated alcohols (Eq. 8.56).135 Lanthanide triflate-promoted indium-mediated allylation of aminoaldehyde in aqueous media generated (i-airiinoalcohols stereoselectively.136 Indium-mediated intramolecular carbocyclization in aqueous media generated fused a-methylene-y-butyrolactones (Eq. 8.57).137 Forsythe and co-workers applied the indium-mediated allylation in the synthesis of an advanced intermediate for azaspiracids (Eq. 8.58).138 Other potentially reactive functionalities such as azide, enone, and ketone did not compete with aldehyde for the reaction with the in situ-generated organo-indium intermediate. 

TrifiuorocLhyl ethers and esters are commonly encountered because of the ready availability of trifluoroethanol and trifluoroethyl halides. The ethers and alcohols are shielded to a similar degree, with sulfides less so (Scheme 5.9). Again whether the trifluoromethyl ethers... 

Trifluoroethylfurans can be obtained from (Z)-2-alkynyl-3-trifluoromethyl allylic alcohols 75 through palladium-catalyzed cyclization-isomerization procedures <00JOC2003>. 

Esterification of chiral alcohols with (R)-(+)-a-methoxy-a-(trifluoromethyl)-... 

The reactions appear to be similar to organometallic synthesis, where the reduction is performed by the metal instead of electricity. However, these reactions have been shown to be essentially different from the corresponding organometallic reactions. This method has valuable advantages. As the anode reaction is controlled, an undivided cell can be used, the reaction occurs in one-step, the conditions are quite simple, and so on. Sibille and Perichon et al. have found that the sacrificial zinc anode is quite effective for trifluoromethylation of aldehydes to form trifluoromethylated alcohols in almost quantitative yields (Eq. 6) [19]. The reaction proceeds via the reduction of Zinc(II) salts, followed by a chemical reaction between the reduced metal, CF3Br, and aldehyde. 

The application of this method to trifluoromethyl analogues has been reported [116]. Trifluoromethylpropargylic mesylates undergo highly selective conversion to allenylzinc reagents, which add in situ to aldehydes producing the expected anti homopropargyl alcohols (Eqs. 9.136 and 9.137). 

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