2-octanol kinetic resolution

In another study a hyperthermophilic esterase from Aeropyrum pemix K1 (APE1547) was used as a catalyst in the hydrolytic kinetic resolution of rac-3-octanol acetate [53]. Following a single round of epPCR, a mutant displaying a 2.6-fold increase in enantioselectivity was identified having five amino acid substitutions, which were shown to be spatially distal to the catalytic center. 

Until quite recently the isolation of optically active seienoxides has been limited to those contained in steroids (isolated as diastereoisomeis). < The difficulty in obtaining these compounds was attributed to the racemization through the achiral hydrated intermediates. Simple optically active sel enoxides (S-11% ee) were first prepared by kinetic resolution. Direct oxidation of selenides to seienoxides was first reported using optically active oxaziridine derivatives under anhydrous conditions, but the extent of the asymmetric induction was somewhat unsatisfactory with methyl phenyl selenide as substrate (8-9% Recently much improved enantiomeric excesses (45-73%) were achieved with new oxaziridine reagents such as (70). An attempt at the asymmetric oxidation of more bulky selenides was independently carried out using Bu OCl in the presence of (-)-2-octanol (equation 55), but resulted in unsatisfactory enantioselectivities (ee 1%). Much better results were obtained by the oxidation of p-oxyalkyl aryl selenides (ee 18-40% equation 56) 27 gjyj selenides (ee 1-28%) using... 

Likewise, various kinetic resolutions of fluorinated compounds have been achieved, e.g. the acetate of l,l,l-trifluoro-2-octanol has been transformed into (/ )- ,1,1-trifluoro-2-octanol (Figure 1.8). 

Biochemical methods are of increasing importance for the large scale production of such chiral alcohols. Here only the kinetic resolution of 2-butanol 1, 2-octanol 2, and 1-phenylethanol 4 by transesterification with tributyrine. catalyzed by a lipase from Candida cylindracea10, will be mentioned. 

Figure 11 Separation of (S)-2-octanol from (R)-2-methylhexyl dodecanoate from CAL B catalyzed kinetic resolution in [BMIMKNTfj] by extraction with CO2 (60 C, 9 MPa) [69],...

In 2005, Cong et al. developed a new method for the resolution of 2-octanol by combining a DKR with a double kinetic resolution. Indeed, the method was based on the feasibility of using the residue of one double kinetic resolution as the substrate of the next double kinetic resolution, etc., and recycling them to DKR. In these conditions, an 80% racemic substrate could be converted to enantiopure products as depicted in Scheme 3.31. 

Qiu, J., Su, E., and Wang, W. (2014). High yield synthesis of D-phenylglycine and its derivatives by nitrilase mediated d5mamic kinetic resolution in aqueous-l-octanol biphasic system. Tetrahedron Letters, 55,1448-1451. 

Numerous examples exist on the kinetic resolution of chiral acyl acceptors. Among other compounds primary and secondary alcohols, various amines, and peroxides have been resolved. Representative examples are shown in Scheme 7. The secondary alcohol 2-octanol was resolved using S-ethyl octanethioate as acyl donor and C. antarctica lipase B [12]. The alkyl peroxide was acylated with isopropenyl acetate using P. cepacia lipase [87]. The primary amine was resolved by C. antarctica lipase B-catalyzed acylation of ethyl octanoate at reduced pressure [88]. The primary alcohol was successfully resolved by acylation of vinyl acetate at — 40 C [89]. 

Table 2 Candida antarctica Lipase B-Catalyzed Kinetic Resolution of 2-Octanol Using Various Acyl Donors ...

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