Asymmetric Transfer Hydrogenation of α-Substituted-β-Keto Carbonitriles via Dynamic Kinetic Resolution,Journal of the American Chemical Society

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Asymmetric Transfer Hydrogenation of α-Substituted-β-Keto Carbonitriles via Dynamic Kinetic Resolution
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2021-02-02 , DOI: 10.1021/jacs.0c13273
Fangyuan Wang _{1,

2} , Tilong Yang ₂ , Ting Wu ₃ , Long-Sheng Zheng ₂ , Congcong Yin ₂ , Yongjie Shi ₂ , Xiang-Yu Ye ₂ , Gen-Qiang Chen , Xumu Zhang

Affiliation

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.

中文翻译：

动态动力学拆分法对α-取代-β-酮腈进行不对称加氢

描述了用于α-取代的-β-酮腈的对映体和非对映体选择性还原的催化方案。该反应涉及DKR-ATH方法，该方法同时构建具有两个连续的立体异构中心的β-羟基甲腈支架。以高产率（94％–98％）和出色的对映和非对映选择性（高达> 99％ee，高达> 99：1 dr）获得了多种α-取代-β-酮腈。非对映选择性的起源也通过DFT计算得到了合理化。此外，这种方法可以快速获得异戊ox酮和他喷他多的药物中间体。

更新日期：2021-02-17

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