PUB - Publikationen an der Universität Bielefeld

Driven by the growing interest in the synthesis of enantiomerically pure biaryl compounds, we report herein a commercial porcine liver esterase (PLE)-catalyzed atroposelective ring-opening reaction of a racemic lactone-bridged biaryl, providing a biaryl carboxylic acid. A distinctive feature of this method is that the substrate bearing low rotational barrier (Delta G double dagger(rot) = 21.9 kcal/mol) undergoes rapid racemization at 30 degrees C, whereas the resulting ring-opened product is conformationally stable (Delta G double dagger(rot) = 30.5 kcal/mol). Consequently, the intrinsic rotational properties of both the substrate and the product enable a dynamic kinetic resolution without the need for an external racemization catalyst. Remarkably, the use of a mixture of a water-immiscible organic cosolvent, such as cyclopentyl methyl ether, and a buffer solution as reaction medium significantly increased the enantioselectivity of the PLE-catalyzed reaction to give the biaryl product (>90% yield) with 65% ee. Furthermore, it was concluded that among the several isoenzymes present in the commercial crude PLE, the lactone hydrolysis is primarily catalyzed by its isoenzymes PLE-5 and PLE-6.