Trifluoromethyl group alcohol

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

Other functional groups tolerated in these isomerizations are ethers [65], alcohols [38, 66-69], propargylic trifluoromethyl groups [70], conjugated enones such as 36 [71] and esters [72] (Scheme 1.14). 

The construction of an indolizidine skeleton has been successfully obtained by radical cyclizations mediated by (TMS)3SiH. Reaction (7.44) represented a key step in the total synthesis of (—)-slaframine. The two pairs of diastereomers were first separated and then hydrolysed to the corresponding alcohols in a 76% overall yield [55]. On the other hand the cyclization of the A-iodopropyl pyridinones in Reaction (7.45) occurs smoothly at room temperature using Et3B/02 as initiator, to give the desired products with a trifluoromethyl group at the bridgehead position in a syn/anti ratio of 7 3 [56]. 

Yeast-mediated reductions predominantly form a single enantiomer and it is often difficult to find conditions which produce the opposite stereoisomer selectively. It has, however, been possible to obtain both enantiomers in 50% yield in 100% via enzymatic optical resolution. Chiral fluorinated secondary alcohols possessing the mono-, di- and/or trifluoromethyl group have been prepared by enzyme-catalyzed kinetic resolutions [27]. 

Though not available commercially, trifluoronitroethane shows some interesting chemistry consistent with the powerful electron-withdrawing effect exerted by the nitro group. Fluoride-mediated nitroaldol reactions were reported [144] with aldehydes affording a valuable entry to trifluoromethyl amino alcohols... 

Bromine trifluoride has found application in the conversion of (methylsulfanyl)thiocar-bonyl groups, bonded to carbon atoms in aromatic rings, oxygen atoms in alcohols and phenols, or to the phthalimide nitrogen atom, into trifluoromethyl groups.125... 

Placement of a trifluoromethyl group on the terminal position of the allylie fragment results in the preparation of ethyl /T(trifluoromethyl)alk-4-enoates. Allylie alcohols 7 are thus converted into esters 8 in moderate to good yields.34 Both ( )- and (Z)-7a give the ( )-hept-4-enoate, (E)-8a. 

A vanety of secondary alcohols with terminal trifluoromethyl group are oxidized by the Dess-Martin periodinane reagent [52 53] (equation 48) Conversion of l,6-anhydro-4-0-benzyl-2 deoxy 2-fluoro-p-D-glucopyranose to the corresponding oxo derivative is earned out by ruthenium tetroxide generated in situ from ruthenium dioxide [54] (equation 49)... 

Muller, N., When Is a Trifluoromethyl Group More Lipophilic Than a Methyl Group Partition Coefficients and Selected Chemical Shifts of Aliphatic Alcohols and Trifluor-oalcohols. J. Pharm. Sci., 1986 75, 987-991. 

Nagai, T. Nishioka, G. Koyama, M. Ando, A. Miki, T. Kumadaki, I. Reactions of trifluoromethyl ketones. IX. Investigation of the steric effect of a trifluoromethyl group based on the stereochemistry on the dehydration of trifluoromethyl homoallyl alcohols./. Fluorine Chem. 1992, 57, 229-237. 

The palladium-catalyzed cyclization of ( )-3-alkynyl-3-trifluoromethyl allylic alcohols proceeds via a favourable 6-endo-dig cyclization due to the electron withdrawing properties of the trifluoromethyl group to afford 4-trifluoro-methyl-27/-pyrans (Equation 8) <2000TL7727>. 

Best results were obtained when HFIP (42) was added. Furthermore, this conversion is very clean and 2,4-dimethylphenol (37) is transformed to 38 in 47% yield. Application of abundant electric current renders a lower yield and product quality of 38. A trifluoromethyl group of the additive can be substituted by a phenyl moiety in order to stabilize the oxyl spin center. Therefore, alcohol 43 provides results similar to the additive HFIP. In conclusion, the chemical yield reached about 50%, a maximum when a current of 1—1.3 F was applied per mole 37 and represents a reasonable compromise between yield and current efficiency [27] (Scheme 19) (Table 2). 

Fluoro-2-trifluoromethylthiazolo[3,2-a]benzimidazol-3(2//)-one (508 A = benzimidazole nucleus, R = F, R = CF3), on heating in alcohol even for a short period, undergoes alcoholysis to give ester 512. The electron-withdrawing nature of the fluorine and trifluoromethyl groups at... 

Asymmetric hydrogenation of either a carbonyl or an imino group to a hydroxyl group or an amino group has frequently been employed for the introduction of chirality in amino acid syntheses. Corey s catecolborane-oxazaborolidine protocol enables transformation of difluoromethyl ketone 1 into alcohol 2 with excellent enantioselectivity. The reaction of diastereoselective amination of a-hydroxyaldehyde 3 with A,A-diallylamine and 2-furyl-boronic acid provides furyl amino alcohol 4 in good chemical yield along with excellent diastereoselectivity. This protocol is applicable for the preparation of amino acids and amino alcohols with a trifluoromethyl group by the combination of /V,/V-diallyl or N,N-dibenzyl amine and aromatic, heteroaromatic and alkenyl boronic acids [7]. The usual chemical transformations as shown in steps 5 to 8 in Scheme 9.1 lead to (2S,3R) difluorothreonine 5 [8]. 

Treatment of trifluoromethyl(trimethyl)silane with fhe fused salt gives the tri-fluoromefhyl anion-equivalent species. This adds to the aldehyde in good yield to form fhe alcohol wifh a trifluoromethyl group (Scheme 2.11). 

Nucleophilic addition of the trifluoromethyl group to aldehydes, ketones and other carbonyl compounds leads primarily to the corresponding trimethylsilyl ether this must subsequently be hydrolyzed to the alcohol. Because typical reaction conditions are very mild, the method is widely applicable, even for sensitive substrates. In contrast with most other methods, fluoride-induced perfluoroalkylation via silicon compounds also works for enolizable carbonyl compounds. With c(, -un-saturated substrates 1,2-addition directly to the carbonyl group is strongly preferred [64b]. If the oxygen is coordinated to a bulky Lewis acid, for example aluminum tri(2,6-bis(tert-butyl)phenoxide (ATPH), the 1,4-addition products are obtained selectively [73f] (Scheme 2.128). 

Kovacs, A., and Hargittai, I., Hydrogen bonding interactions of the trifluoromethyl group 2-trifluoromethylvinyl alcohol, Int. J. Quantum Chem., 62, 645-652 (1997). 

The successive replacement of hydrogen in methanol with trifluoromethyl groups increases acidities of the alcohols by about 3 pKa units (Table 1.10) [7]. Because of the small... 

The Li—F chelation is also useful for stereoselective reactions. In particular, chelation between lithium of enolates and a fluorine of a trifluoromethyl group results in conformational fixation of substrates, leading to markedly enhanced stereoselection. This concept has often been employed to achieve stereocontrol in fluorinated enolate chemistry. Morisawa reported Li—F chelation-controlled stereoselective a-hydroxylation of enolate of 40 [22]. The oxidant approaches from the less hindered side of the Li—F chelated enolate intermediate (41), affording anti-alcohol (42) exclusively (Scheme 3.11). The syn-alcohol (45) was prepared by NaBlrh reduction of ketoester (43) via a reaction course predicted by Felkin-Anh s model (44). 

Table IV contains selected examples of the enzymatic resolution of esters with various structures. As was discussed above, enhancement of the optical purity was possible by changing the acyl group or the enzyme (Run 1,2 or 6,7). Noteworthy is the fact that acetate 5 with a trifluoromethyl group was converted by lipase MY into the alcohol with (R) absolute configuration without exception in every case, when the stereochemistry has been determined. However, substrates with the other fluorine-containing substituents furnished alcohols whose asymmetric configuration depended on their structures. Particularly interesting is the relationship between Runs 4 and 5 (18), when resolution was accompanied with simultaneous separation of diastereomers. To the best of our knowledge, this is the first example of the type of resolution of both diastereomers and enantiomers by enzymatic hydrolysis in a single transformation.

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