PhAA0H

Lipase PS-C ll Organic solvent ii^OCOR

(R)-14a: R = CH3 (R)-14b: R = (CH2)2CH3 (R)-14c: R = (CH2)2Ph

Scheme 3: Resolution of (±)-5-(hydroxymethyl)-3-phenyl-2-isoxazoline

Figure 13: Temperature effect in lipase PS-C Il-catalyzed resolution of (±)-13 with vinyl acetate (•), vinyl butyrate (■), and vinyl 3-phenylpropanoate (▲) in acetone.

Figure 13: Temperature effect in lipase PS-C Il-catalyzed resolution of (±)-13 with vinyl acetate (•), vinyl butyrate (■), and vinyl 3-phenylpropanoate (▲) in acetone.

4.8. Application of temperature control to asymmetric protonation8

The low-temperature method is effective not only in the kinetic resolution of alcohols but also in the enantioface-selective asymmetric protonation of enol acetate of 2-methylcyclohexanone (15) giving (R)-2-methylcyclohexanone (16).8 The reaction in H2O at 30°C gave 28% ee (98% conv.), which was improved up to 77% ee (82% conv.) by the reaction using lipase PS-C II in i-Pr2O and ethanol at 0°C. Acceleration of the reaction with lipase PS-C II made this reaction possible because this reaction required a long reaction time. The temperature effect is shown in Fig. 14. The regular temperature effect was not observed. The protons may be supplied from H2O, methanol, or ethanol, whose bulkiness is important.

4.9. Lipase-catalyzed resolutions at high temperatures up to 120° C

Lipase Amano PS-C II was also found to be useful for a high-temperature reaction in the resolution of a bulky substrate, 1,1-diphenyl-2-propanol, which showed no reactivity under usual conditions with lipase PS.7 An enantiopure product was obtained at 40-120°C, and the highest conversion (39%) was obtained at 80-90°C. It is very interesting that a single enzyme is usable in the reaction at a very wide range of temperatures from —80°C to 120°C.

5. LOW-TEMPERATURE REACTIONS IN LITERATURES

Recently, temperature control of enantioselectivity is actively studied,34-62 and many examples for the low-temperature reactions have been published. The typical examples for the synthetic purpose are summarized in Fig. 15. The E values of these are generally increased by lowering the temperature. Compound 29 is used

Lipase PS-C ll

Figure 14: Lipase-catalyzed enantioface-selective asymmetric protonation.

in a media of supercritical CO2. Compounds 36 are used for the kinetic resolution in the hydrolysis of nitrile and amide, and compound 37 is for the reaction in the hydrolytic ring opening of epoxide. Interestingly, some examples show rather negative temperature effect as shown in Fig. 16. The latter examples may be due to the entropy-driven reactions,6 and are also interesting.

BnO"

"OTBS

"OTBS

88 127

HaC.

1936

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