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.
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。
