Department of Chemistry and Shenzhen Grubbs Institute, Southern University of Science and Technology, Shenzhen, 518000, China.
Academy for Advanced Interdisciplinary Studies, Southern University of Science and Technology, Shenzhen, 518000, China.
J Am Chem Soc. 2022 Oct 5;144(39):17763-17768. doi: 10.1021/jacs.2c07506. Epub 2022 Sep 27.
Due to their low reactivity, difficult enantiocontrol, and proneness to N-O bond cleavage, the catalytic asymmetric hydrogenation of oximes to hydroxylamines has remained a significant challenge. Herein, a Lewis and Brønsted acid cooperation strategy was established for the asymmetric hydrogenation of oximes, providing the corresponding hydroxylamines with up to 95% yield and up to 96% ee. Addition of Lewis and Brønsted acid was crucial to obtain high conversion and enantioselectivity. Mechanistic investigations indicates that the thiourea fragment of the ligand, Lewis acid (In(OTf) or Zn(OAc)), as well as the Brønsted acid (l-CSA) played vital roles in the control of reactivity and enantioselectivity of the reaction. In addition, the synthetic elaboration of this transformation was demonstrated by gram scale experiment with retention of the yield and enantioselectivity.
由于其低反应性、难以控制对映选择性以及易于发生 N-O 键断裂，肟的催化不对称氢化反应仍然是一个重大挑战。在此，建立了路易斯酸和布朗斯台德酸的协同作用策略，用于肟的不对称氢化反应，以高达 95%的收率和高达 96%的对映选择性得到相应的羟胺。路易斯酸和布朗斯台德酸的添加对于获得高转化率和对映选择性至关重要。机理研究表明，配体的硫脲片段、路易斯酸（In(OTf)或 Zn(OAc))以及布朗斯台德酸（l-CSA）在控制反应的活性和对映选择性方面发挥了重要作用。此外，通过克级实验证明了该转化的合成改进，收率和对映选择性保持不变。
