Trifluoroethyl butyrate

The sterically rather demanding racemic binaphthylalkylamines 126 and 127 can be efficiently resolved in diisopropyl ether using Pseudomonas aeruginosa lipase (LIP) as catalyst and trifluoroethyl butyrate as acylating agent for 126 and ethyl butyrate for 127 (Scheme 4.38) [125]. 

For the P-aminocarboxamides 134-137, CALA gave very low enantioselectivity. Because no ester function was present in the substrate, N-acylation proceeded satisfactory with CALB as the catalyst and trifluoroethyl butyrate as the acyl donor in t-butylmethyl ether/t-amylalcohol (TBME)/(TAME) mixtures at 45 °C (Scheme 4.40) [131]. 

The enantiopreference of the protease subtilisin in the acylalion of chiral alcohols is known to be opposite to that observed with lipases, providing for access to both enantiomers with DKR, depending on the enzyme used [137, 138, 139]. Acylation using 2,2,2-trifluoroethyl butyrate as the acyl donor was combined with in situ racemization, affording the corresponding esters in high yield and [135]. 

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). 

Unprotected racemic amines can be resolved by enantioselective acylations with activated esters (110,111). This approach is based on the discovery that enantioselectivity of some enzymes strongly depends on the nature of the reaction medium. For example, the enantioselectivity factor (defined as the ratio of the initial rates for (5)- and (R)-isomers) of subtilisin in the acylation of a-methyl-benzylamine with trifluoroethyl butyrate varies from 0.95 in toluene to 7.7 in 3-methyl-3-pentanol (110). The latter solvent has been used for enantioselective resolutions of a number of racemic amines (110). 

A synthetic precursor to monoamine oxidase (MAO) inhibitors, ( ) 1 aminoindan 10, was produced using a continuous flow column bioreactor containing subtilisin immobilized on glass beads [9]. The process was run in 3 methyl 3 pentanol and utilized the active ester 2,2,2 trifluoroethyl butyrate 11 as the acylating agent to give amide 12 (Figure 14.6). 

More recently, BackvalFs group reported the DKR of the jS-amino ester, ethyl 3-amino-3-phenylpropanoate, using Candida antarctica lipase A (CAL-A) immobilised in mesocellular foam (GamP-MCF) in combination with the methoxy analogue of Shvo s catalyst at 90°C. It was shown that the use of 2,4-dimethyl-3-pentanol as a hydrogen donor allowed side product formation to be suppressed. Thus, the reaction performed in the presence of trifluoroethyl butyrate as the acyl donor provided the corresponding (5)-amide in 85% yield and 89% ee. 

In 2011, Shvo s catalyst was used in combination with triacylglycerol lipase (TL) by Alcantara et al. in the DKR of benzoin. The reaction was carried out in 2-methyltetrahydrofuran as the solvent in the presence of 5 mol% of Shvo s catalyst, lipase TL, and trifluoroethyl butyrate as acyl donor at 55 °C. Under these conditions, the corresponding (5 )-butyrate was obtained in 85% yield combined with >99% ee, as shown in Scheme 8.52. 

Hoyos et al. achieved the DKR of benzoins using P. stutzeri lipase (PSL trade name, lipase TL) and 1 in the presence of trifluoroethyl butyrate as the acyl donor (Scheme 5.12 and Chart 5.9) [17]. It is noted that benzoins are poorly reactive with Novoz3un 435 and lipase PS because they have two sterically demanding substituents at tire hydroxymethine center. 

TFEB 2,2,2-trifluoroethyl butyrate sulfonic acid) trisodium salt... 

Enzymatic acyl transfer reactions are also practical processes for the acylation of hydroxyl groups in steroids [25]. The lipase from Chromobacterium viscosum (CVL), for instance, selectively transfers butyric acid from trifluoroethyl butyrate to equatorial 3p-alcoholic functions being present in a variety of sterols, such as 107, 110, and 113 (Table 9). Axially oriented alcohols at C-3 and secondary alcohols at C-17 (107 and 110) or in the sterol side chains (113) are not derivatized. In addition to the equatorial alcohols, the... 

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