Oono Masato, Yamada Akane, Kimura Masanari, Kanomata Kyohei, Akai Shuji
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Research Foundation Itsuu Laboratory, C1232 Kanagawa Science Park R & D Building, 3-2-1 Sakado Takatsu-ku, Kawasaki, Kanagawa, 213-0012, Japan.
Chemistry. 2025 May;31(25):e202404406. doi: 10.1002/chem.202404406. Epub 2025 Apr 11.
Dynamic kinetic resolution (DKR) by combining lipase-catalyzed esterification of racemic sec-alcohols and in situ racemization has been widely studied; however, reports on DKR involving lipase-catalyzed hydrolysis of racemic esters are scarce. This problem is probably due to the lack of more effective and general racemization methods. Herein, we report the enhanced hydrolytic DKR of racemic allylic esters. The discovery of the monodentate ligand P[CH-2,6-(OMe)], which in situ generates Pd complex(es) highly reactive to racemization and the NaOAc-mediated acceleration of racemization, are notable breakthroughs. Consequently, the DKR of racemic allylic esters can be completed in a few hours at 40 °C in most cases, yielding optically active allylic alcohols (93 % ee to >99 % ee) in 58-91 % isolated yields with minimal side reactions.
通过将脂肪酶催化的外消旋仲醇酯化反应与原位外消旋化相结合的动态动力学拆分（DKR）已得到广泛研究；然而，关于涉及脂肪酶催化外消旋酯水解的DKR的报道却很少。这个问题可能是由于缺乏更有效和通用的外消旋化方法。在此，我们报道了外消旋烯丙基酯的增强水解DKR。单齿配体P[CH-2,6-(OMe)]的发现是显著的突破，它能原位生成对外消旋化具有高反应活性的钯配合物，以及NaOAc介导的外消旋化加速作用。因此，在大多数情况下，外消旋烯丙基酯的DKR能在40℃下几小时内完成，以58 - 91%的分离产率得到光学活性的烯丙醇（对映体过量率为93% ee至>99% ee），且副反应最少。
