The Highly Selective Equatorial Hydride Delivery by Biocatalysis: Chemoenzymatic Synthesis of <i>trans</i>-2-(4-Propylcyclohexyl)-1,3-propanediol via <i>cis</i>-4-Propylcyclohexanol

Abstract

4-Propylcyclohexanone 10a (69 g/L) is reduced by the catalysis of Galactomyces geotrichum JCM 6359 using i-PrOH (4.0 equiv) as an auxiliary substrate for recycling externally supplemented NAD+ (0.001 equiv) in 40 mM potassium phosphate buffer (pH 7.5) for 20 h to provide a mixture of cis-4-propylcyclohexanol 3a [cis/trans (99:0.5); 74%] and unconsumed 10a (22%). Practically pure 3a can be isolated in 69% yield after removing the entailed ketone 10a via bisulfite adduct formation. In the meantime, the crude reduction product [3a/10a (74:22)], without further purification, can be elaborated into trans-2-(4-propylcyclohexyl)-1,3-propanediol 1a, a compound deemed versatile in liquid-crystals development, in 30% overall yield from 10a in four steps.