Zhang Jie, Wang Kun, Zhu Can
Department of Chemistry, Fudan University, 2005 Songhu Road, Shanghai 200438, China.
JACS Au. 2024 Jan 17;4(2):502-511. doi: 10.1021/jacsau.3c00623. eCollection 2024 Feb 26.
Atropisomeric biaryls have found crucial applications in versatile chiral catalysts as well as in ligands for transition metals. Herein, we have developed an efficient crystallization-induced deracemization (CID) method to access chiral biaryls from their racemates with a chiral ammonium salt under copper catalysis including BINOL, NOBIN, and BINAM derivatives. After being significantly accelerated by its bidentate diamine ligand, the copper catalyst exhibits high efficiency and selectivity in racemizing biaryl skeletons, and the cocrystal complex would be enantioselectively formed together with chiral ammonium salt, which on acid-quenching would directly deliver chiral biaryl without further chromatographic purification. This CID process is easily scalable, and the chiral ammonium salt was nicely recoverable. Ligand effect studies showed that bulky alkyl substitution was an indispensable element to ensure efficient racemization, which probably proceeds via a radical-cation intermediate and further allows axial rotation by forming a delocalized radical.
轴手性联芳基化合物在多种手性催化剂以及过渡金属配体中有着至关重要的应用。在此，我们开发了一种高效的结晶诱导去消旋化（CID）方法，在铜催化下，使用手性铵盐从其外消旋体中获得手性联芳基化合物，包括联萘酚（BINOL）、联萘胺（NOBIN）和联萘二甲酰胺（BINAM）衍生物。在其二齿二胺配体的显著加速作用下，铜催化剂在使联芳基骨架外消旋化方面表现出高效率和选择性，并且共晶复合物会与手性铵盐一起对映选择性地形成，在酸淬灭后，无需进一步的柱色谱纯化即可直接得到手性联芳基化合物。这种CID过程易于放大，并且手性铵盐可很好地回收。配体效应研究表明，庞大的烷基取代是确保高效外消旋化不可或缺的因素，其可能通过自由基阳离子中间体进行，并且通过形成离域自由基进一步允许轴向旋转。
