Interdisciplinary Research Center for Catalytic Chemistry, National Institute of Advanced Industrial Science and Technology (AIST), Central 5, Higashi 1-1-1, Tsukuba, Ibaraki, 305-8565, Japan.
Research Institute of Chemical Process Technology, National Institute of Advanced Industrial Science and Technology (AIST), Nigatake 4-2-1, Sendai, Miyagi, 983-8551, Japan.
Chemistry. 2021 Jul 26;27(42):10844-10848. doi: 10.1002/chem.202101439. Epub 2021 May 28.
The N-arylation of chiral amino acid esters with minimal racemization is a challenging transformation because of the sensitivity of the α-stereocenter. A versatile synthetic method was developed to prepare N-arylated amino acid esters using cyclohexanones as aryl sources under continuous-flow conditions. The designed flow system, which consists of a coil reactor and a packed-bed reactor containing a Pd(OH) /C catalyst, efficiently afforded the desired N-arylated amino acids without significant racemization, accompanied by only small amounts of easily removable co-products (i. e., H O and alkanes). The efficiency and robustness of this method allowed for the continuous synthesis of the desired product in very high yield and enantiopurity with high space-time yield (74.1 g L h ) and turnover frequency (5.9 h ) for at least 3 days.
手性氨基酸酯的 N-芳基化反应是一种具有挑战性的转化，因为α-立体中心很敏感。开发了一种通用的合成方法，在连续流条件下使用环己酮作为芳基源制备 N-芳基化氨基酸酯。设计的流动系统由一个盘管反应器和一个填充床反应器组成，其中包含 Pd(OH) /C 催化剂，能够有效地提供所需的 N-芳基化氨基酸，而没有明显的外消旋化，同时仅生成少量易于去除的副产物（即 H 2 O 和烷烃）。该方法的效率和稳健性允许以非常高的产率和对映体纯度连续合成所需的产物，时空收率（74.1 g·L -1 ·h -1 ）和转化频率（5.9 h -1 ）高，至少连续运行 3 天。
