通过动态动力学拆分实现α-取代-β-酮腈的不对称转移氢化。
Asymmetric Transfer Hydrogenation of α-Substituted-β-Keto Carbonitriles via Dynamic Kinetic Resolution.
机构信息
School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, People's Republic of China.
Department of Chemistry, Southern University of Science and Technology, Shenzhen, People's Republic of China.
出版信息
J Am Chem Soc. 2021 Feb 17;143(6):2477-2483. doi: 10.1021/jacs.0c13273. Epub 2021 Feb 2.
A catalytic protocol for the enantio- and diastereoselective reduction of α-substituted-β-keto carbonitriles is described. The reaction involves a DKR-ATH process with the simultaneous construction of β-hydroxy carbonitrile scaffolds with two contiguous stereogenic centers. A wide range of α-substituted-β-keto carbonitriles were obtained in high yields (94%-98%) and excellent enantio- and diastereoselectivities (up to >99% ee, up to >99:1 dr). The origin of the diastereoselectivity was also rationalized by DFT calculations. Furthermore, this methodology offers rapid access to the pharmaceutical intermediates of Ipenoxazone and Tapentadol.
描述了一种用于对 α-取代-β-酮基腈进行对映选择性和非对映选择性还原的催化方案。该反应涉及 DKR-ATH 过程，同时构建具有两个相邻手性中心的 β-羟基腈支架。各种 α-取代-β-酮基腈以高产率（94%-98%）和优异的对映选择性和非对映选择性（高达>99%ee，高达>99:1dr）获得。通过 DFT 计算也合理地解释了非对映选择性的起源。此外，该方法还提供了快速获得 Ipenoxazone 和 Tapentadol 药物中间体的途径。
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