Porcine Liver Esterase‐Catalyzed Dynamic Kinetic Resolution of a Lactone‐Bridged Biaryl: Impact of Organic Cosolvents on Enantioselectivity

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 (Δ G ‡ rot = 21.9 kcal/mol) undergoes rapid racemization at 30°C, whereas the resulting ring‐opened product is conformationally stable (Δ G ‡ 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.