Trifluoroethyl group esters

An example of CF3 bound to boron in a boronic ester is provided in Scheme 5.27, as is an example of a boronic ester with the CF3 group one carbon away. The fluorines of this trifluoroethyl group are perhaps the most deshielded of any CF3 group bound to a saturated carbon. 

In this contribution, we will only consider polymers with longer i/segments (alkyl and perfluoroalkyl units directly linked via C—C— bond, not by functional groups like ester, amide, and urethane as, for instance, in References 39 and 40). Only /segments able to self-organize will be discussed. We will comment only briefly on polymers with short i/groups such as trifluoroethyl groups. Reviews about this polymer type... 

Nucleophilic participation is important only for esters of alcohols that have pK <13. Specifically, phenyl and trifluoroethyl esters show nucleophilic catalysis, but methyl and 2-chloroethyl esters do not. This result reflects the fete of the tetrahedral intermediate that results fi om nucleophilic participation. For relatively acidic alcohols, the alkoxide group can be eliminated, leading to hydrolysis via nucleophilic catalysis ... 

DKR of esters bearing an electron-withdrawing group at the ot-carbon can be performed easily under mild reaction conditions due to the low pKa of the oc-proton. Tsai et al. have reported an efficient DKR of rac-2,2,2-trifluoroethyl ot-chorophenyl acetate in water-saturated isooctane [40]. They used lipase MY from C. rugosa for the KR and trioctylamine as the base for racemization. (R)-chlorophenylacetic acid was obtained in 93% yield and 89.5% ee (Figure 4.15). 

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]. 

A number of steroids have been regioselectively acylated in a similar manner (99,104). Chromobacterium viscosum lipase esterifies 5a-androstane-3p,17p-diol [571-20-0] (75) with 2,2,2-trifluoroethyl butyrate in acetone with high selectivity. The lipase acylates exclusively the hydroxy group in the 3-position giving the 3p-(monobutyryl ester) of (75) in 83% yield. In contrast, bacillus subtilis protease (subtilisin) displays a marked preference for the C-17 hydroxyl. Candida cylindracea lipase (CCL) suspended in anhydrous benzene regioselectively acylates the 3a-hydroxyl group of several bile acid derivatives (104). 

Kanerva et al. resolved ethyl esters of ten alicyclic (i-aminocarboxylic acids by lipase catalysis in organic solvents. The resolutions were based on acylation of the amino group at the / -stereogenic centre with various 2,2,2-trifluoroethyl esters. From the cis and trans racemic esters 42, all four enantiomers of 2-ACPC were prepared. The absolute configurations of 43 and 44 were proved by transformation to the known 2-ACPC enantiomers by hydrolysis and subsequent desalting with an anion-exchange resin [85]. 

A different approach to the synthesis of the protected hydroxy amino acid moiety was also described by Broady et al (ref.127) (see Scheme 7). Construction was from the IJ-lactam aldehyde (78) prepared from L-aspartic acid. Condensation of (78) with benzyl bis (2, 2,2-trifluoroethyl)phosphonoacetate (79) afforded the (Z)-ester (80) along with a small amount (11%) of (E)-isomer. The hydroxyl substituents were introduced by cis-hydroxylation using catalytic osmylation in the presence of NMO. This reaction was found to be moderately stereoselective and gave a mixture of diastereomers in the ratio ca. 80 20 with the major product being the correct diastereomer (81). The diol group was protected as the... 

Chiral intermediates for the synthesis of (-)-anisomycin (1) and (+)-anisomycin (anti-1) (153), (R)-2-(p-methoxyphenyl)methyl-2,5-dihydro-pyrrole (142) and its (S)-isomer (+)-187, have been efficiently synthesized from D-tyrosine and L-tyrosine, respectively (Scheme 20) [28]. D-tyrosine was converted to 0-methyl D-tyrosine methyl ester (182) [72-75] which was treated with di-tert-butyl dicarbonate to protect the amino group. Subsequent reduction of the ester group with sodium borohydride in the presence of lithium chloride furnished the alcohol 183. Swern oxidation of 183 followed by chain extension with the anion derived from bis(2,2,2-trifluoroethyl)(ethoxycarbonylmethyl)-phosphonate afforded (Z)-Q ,/0-unsaturated ester (184), which was used immediately without purification to avoid or minimize any possible racemization of the chiral center. Reduction of the ester group of 184 with diisobutylaluminium hydride afforded the alcohol 185 which after mesylation followed by intramolecular cyclization gave the desired 2,5-dihydropyrrole derivative 186. Removal of the tert-butyloxycarbonyl group was achieved by treatment with trifuoroacetic acid to give (-)-142 in 62% overall yield from 182. The (S)-2,5-dihydropyrrole (-l-)-187 was also prepared in the same manner starting from L-tyrosine. Since (-l-)-187 had been transformed into (-l-)-anisomycin (anti-1) (153), (-)-142 could also be transformed to the (-)-anisomycin (1) [26,66]. 

Next, we will introduce several practical or commercial plant activators. These synthetic plant activators include BTH, probenazole, INA, TDL, and some BTH analog trifluoroethyl esters that have been developed at our group. ... 

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