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.
Dhiman et al. (Sun,) studied this question.
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