Dynamic Kinetic Resolution of Azlactones via Phase-Transfer Catalytic Alcoholysis
Dynamic Kinetic Resolution of Azlactones via Phase-Transfer Catalytic Alcoholysis
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DOI：
10.1021/acscatal.1c03076
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发表时间：
2021-11
期刊：
影响因子：
12.9
通讯作者：
Kodai Wakafuji;Satsuki Iwasa;Kina N. Ouchida;Hyemin Cho;H. Dohi;E. Yamamoto;T. Kamachi;M. Tokunaga
中科院分区：
文献类型：
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作者：
Kodai Wakafuji;Satsuki Iwasa;Kina N. Ouchida;Hyemin Cho;H. Dohi;E. Yamamoto;T. Kamachi;M. Tokunaga
采用相转移催化动态动力学拆分法对吖内酯进行不对称醇解反应，得到了相应的α-手性氨基酸酯，产率高达98%，产率高达99：1。此外，该催化体系还用于N-苯甲酰基氨基酸六氟异丙酯的不对称醇解反应，得到了高产率、高立体选择性的目标产物（产率71%，98：2 er）。催化剂的负载量可以减少到0.1摩尔%，而没有显着的立体选择性损失（周转数= 411）。此外，克规模的反应和转化的对映体富集的产品，包括氢解，LAH-还原，Suzuki-Miyaura偶联反应成功地实现。使用伪过渡态（伪TS）构象搜索与ConFinder和密度泛函理论（DFT）计算进行的详细计算研究表明，TS模型解释了立体选择性的起源。在该TS模型中，水或醇分子通过与氮原子的氢键作用活化吖内酯底物，伴随累积的弱相互作用（包括氢键相互作用、C-H−π和π-π相互作用）稳定TS，产生主要对映体。
Phase-transfer catalytic asymmetric alcoholysis of azlactones via dynamic kinetic resolution proceeded for a wide range of alcohols and azlactones, affording the corresponding α-chiral amino acid esters in up to 98% yield and up to 99:1 er. In addition, this catalytic system was also applied to the asymmetric alcoholysis ofN-benzoyl amino acid hexafluoroisopropyl ester providing the desired product in good yield with high stereoselectivity (71% yield, 98:2 er). The catalyst loading could be reduced to 0.1 mol % without significant loss of stereoselectivity (turnover number = 411). Furthermore, a gram-scale reaction and transformations of the enantioenriched products involving hydrogenolysis, LAH-reduction, and Suzuki–Miyaura coupling reactions were successfully achieved. Detailed computational studies using a pseudotransition state (pseudo-TS) conformational search with ConFinder and density functional theory (DFT) calculations indicated a TS model that accounted for the origin of the stereoselectivity. In this TS model, water or alcohol molecules activate the azlactone substrate by H-bonding with the nitrogen atom, and concomitant accumulated weak interactions, including H-bonding interactions, C–H−π, and π–π interactions, stabilize the TS, leading to the major enantiomer.