Vinyl octanoate

Jacobs et al. employed an acidic zeolite catalyst for the racemization of sec-alcohols, which occurs through the formation of carbocations [44] (Figure 4.19). The KR is catalyzed by CALB in the presence of vinyl octanoate as acyl donor. DKR takes place successfully in a biphasic system (octane/H2O, 1 1) at 60 °C. 

The one-pot dynamic kinetic resolution (DKR) of ( )-l-phenylethanol lipase esterification in the presence of zeolite beta followed by saponification leads to (R)-l phenylethanol in 70 % isolated yield at a multi-gram scale. The DKR consists of two parallel reactions kinetic resolution by transesterification with an immobilized biocatalyst (lipase B from Candida antarctica) and in situ racemization over a zeolite beta (Si/Al = 150). With vinyl octanoate as the acyl donor, the desired ester of (R)-l-phenylethanol was obtained with a yield of 80 % and an ee of 98 %. The chiral secondary alcohol can be regenerated from the ester without loss of optical purity. The advantages of this method are that it uses a single liquid phase and both catalysts are solids which can be easily removed by filtration. This makes the method suitable for scale-up. The examples given here describe the multi-gram synthesis of (R)-l-phenylethyl octanoate and the hydrolysis of the ester to obtain pure (R)-l-phenylethanol. 

Vinyl octanoate was obtained from TCI (Tokyo, Japan). All other chemicals with the exception of the zeolite beta are available from Sigma Aldrich. The synthesis of a particularly active modification of low-alumina zeolite beta has been described by us. Commercial material, available as samples from, for example, Zeolyst or Siidchemie can be used, but because of excessive acidity may result in up to 15 % of styrene formation. 

The mixture was left to cool to room temperature and the solid catalysts were removed by filtration. Toluene and the by-product, acetaldehyde, were removed under reduced pressure by using a rotary evaporator. The residue contains the desired product together with unreacted vinyl octanoate and traces of octanoic acid, which are formed by hydrolysis of the vinyl octanoate. The product can be purified by redissolving the residue in hexane (20 mL) and washing it with 0.1 M NaOH (20 mL x 3). The organic layer was dried with anhydrous Na2S04 and the hexane was removed by a rotary evaporator. 

Isopropenyl acetate O Vinyl acetate O Vinyl butanoate O Vinyl octanoate 97 68... 

For example, the DKR of 1-phenylethanol, performed in the presence of VOSO4 combined with CAL-B and vinyl octanoate, yielded the corresponding (R)-ester in 93% yield and 99% ee. The formation of carbenium ion intermediates was suggested because of the results of 0-labeling experiments. 

Acid zeolites have also been tested for the racemisation of alcohols under biphasic conditions. Their scope was found, however, to be limited to benzylic alcohols, since electron-rich benzylic alcohols were not suitable substrates because of the formation of dimers. Under optimised conditions, based on the use of H-Beta zeolite, CAL-B lipase and an excess of vinyl octanoate at 60°C, enantiopure (i )-l-phenylethyl octanoate (>99% ee) was obtained in... 

Acid zeolites have also been tested for the racemisation of alcohols under biphasic conditions.Their scope was found, however, to be limited to benzylic alcohols, since electron-rich benzylic alcohols were not suitable substrates because of the formation of dimers. Under optimised conditions, based on the use of H-Beta zeolite, CALB lipase, and an excess of vinyl octanoate at 60 °C, enantiopure (R)-l-phenylethyl octanoate (>99% ee) was obtained in 90% yield from 1-phenylethanol. In addition, Lozano et al. have recently performed the DKR of this alcohol in the presence of acidic zeolite catalysts (CBV400) in an ionic liquid-supercritical carbon dioxide system with a continuous reaction system. Therefore, when Novozym 435 was employed at 50 °C and 100 bars in the presence of vinylpropanoate as the acyl donor, the expected (R)-phenylethylpropionate was produced in excellent yield of 98% with enantioselectivity of 97% ee and without any activity loss during 14 days of operation. 

In the case of vinyl octanoate, both a high initial rate and a high enantiomeric excess indicates a good displacement of the equilibrium toward product formation. However, it has been reported that there might be a decreased enantioselectivity if the vinyl ester is... 

---