Manganese-Catalyzed Asymmetric Hydrogenation for Atroposelective Dynamic Kinetic Resolution of Heterobiaryl Ketone <i>N</i>‑Oxides

An atroposelective dynamic kinetic resolution of configurationally labile heterobiaryl ketone N-oxides via Mn-catalyzed asymmetric hydrogenation has been disclosed. By use of a structurally finely tuned chiral ferrocenyl P,N,N-ligand, the hydrogenation proceeds smoothly under mild conditions with simultaneous installation of central and axial chirality, giving a wide range of atropisomeric 1-arylisoquinoline and 2-arylpyridine N-oxides bearing a chiral alcohol structure with high diastereo- and enantioselectivities. The diastereomer of the hydrogenation product could be readily prepared in a stereospecific way with the complete inversion of the central chirality via Mitsunobu reaction. The value of this central- and axial-chiral heterobiaryl N-oxide scaffold is preliminarily demonstrated by its successful utility as a chiral catalyst in asymmetric allylation of benzaldehyde with allyltrichlorosilane.本研究报道了一种通过锰（Mn）催化不对称氢化，实现构型易变联芳杂环酮N-氧化物阻转选择性动态动力学拆分的方法。通过使用结构精细调控的手性二茂铁基P,N,N配体，该氢化反应可在温和条件下顺利进行，同时构建中心手性与轴手性，得到一系列兼具手性醇结构的阻转异构1-芳基异喹啉及2-芳基吡啶N-氧化物产物，且均表现出优异的非对映选择性与对映选择性。通过光延反应可实现中心手性的完全翻转，以立体专一性路径便捷制备该氢化产物的非对映异构体。该中心-轴手性联芳杂环N-氧化物骨架的应用价值得到初步验证：其作为手性催化剂成功应用于苯甲醛与三氯烯丙基硅烷的不对称烯丙基化反应。