Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, China.
N.D. Zelinsky Institute of Organic Chemistry Russian Academy of Science, Moscow, Russian Federation.
Nat Chem. 2022 Aug;14(8):920-927. doi: 10.1038/s41557-022-00971-8. Epub 2022 Jun 13.
Chiral hydroxylamines are vital substances in bioscience and versatile subunits in the preparation of a variety of functional molecules. However, asymmetric and non-asymmetric synthetic approaches to these compounds are far from satisfactory. Although atom-economic metal-catalysed asymmetric hydrogenations have been studied for over 50 years, the asymmetric hydrogenation of oximes to the corresponding chiral hydroxylamines remains challenging because of the labile N-O bond and inert C=N bond. Here we report an environmentally friendly, earth-abundant, transition-metal nickel-catalysed asymmetric hydrogenation of oximes, affording the corresponding chiral hydroxylamines with up to 99% yield, 99% e.e. and with a substrate/catalyst ratio of 1,000. Computational results indicate that the weak interactions between the catalyst and substrate play crucial roles not only in the transition states, but also during the approach of the substrate to the catalyst, by selectively reducing the reaction barriers and thus improving the reaction efficiency and securing the generation of chirality.
手性羟胺是生物科学中至关重要的物质，也是制备各种功能分子的多功能亚单位。然而，这些化合物的不对称和非对称合成方法远不能令人满意。尽管原子经济性的金属催化不对称氢化已经研究了 50 多年，但由于肟的 N-O 键不稳定和 C=N 键惰性，其不对称氢化仍然具有挑战性。在这里，我们报道了一种环境友好、丰富的过渡金属镍催化的肟不对称氢化反应，以高达 99%的产率、99%的对映选择性和 1000 的底物/催化剂比，得到相应的手性羟胺。计算结果表明，催化剂和底物之间的弱相互作用不仅在过渡态中，而且在底物接近催化剂的过程中，通过选择性降低反应势垒，从而提高反应效率并确保手性的产生，起着至关重要的作用。
