Singh Vikas Kumar, Zhu Chendan, De Chandra Kanta, Leutzsch Markus, Baldinelli Lorenzo, Mitra Raja, Bistoni Giovanni, List Benjamin
Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, D-45470 Mülheim an der Ruhr, Germany.
Department of Chemistry, Biology and Biotechnology, University of Perugia, 06122 Perugia, Italy.
Science. 2023 Oct 20;382(6668):325-329. doi: 10.1126/science.adj7007. Epub 2023 Oct 19.
Benzylic stereogenic centers are ubiquitous in natural products and pharmaceuticals. A potentially general, though challenging, approach toward their selective creation would be asymmetric unimolecular nucleophilic substitution (S1) reactions that proceed through highly reactive benzylic cations. We now report a broadly applicable solution to this problem by identifying chiral counteranions that pair with secondary benzylic cations to engage in catalytic asymmetric C-C, C-O, and C-N bond-forming reactions with excellent enantioselectivity. The critical cationic intermediate can be accessed from different precursors via Lewis- or Brønsted acid catalysis. Key to our strategy is the use of only weakly basic, confined counteranions that are posited to prolong the lifetime of the carbocation, thereby avoiding nonproductive deprotonation pathways to the corresponding styrene.
苄基手性中心在天然产物和药物中普遍存在。一种潜在通用但具有挑战性的选择性构建苄基手性中心的方法是通过高活性苄基阳离子进行的不对称单分子亲核取代（S1）反应。我们现在报告了一个广泛适用的解决该问题的方案，即通过识别与仲苄基阳离子配对的手性抗衡阴离子，以实现具有优异对映选择性的催化不对称C-C、C-O和C-N键形成反应。关键的阳离子中间体可通过路易斯酸或布朗斯特酸催化从不同前体获得。我们策略的关键是仅使用弱碱性、受限的抗衡阴离子，据推测这些抗衡阴离子可延长碳正离子的寿命，从而避免生成相应苯乙烯的无生产性去质子化途径。
