德国马普煤炭研究所Benjamin List团队报道了催化不对称SN1反应中次苄基阳离子的驯服。相关研究成果发表在2023年10月20日出版的《科学》。

苄基立体生成中心普遍存在于天然产物和药物中。一种潜在的通用但具有挑战性的选择性产生方法是，通过高度反应性的苄基阳离子进行的不对称单分子亲核取代（SN1）反应。

该文中，研究人员报道了一种广泛适用于这个问题的解决方案，通过鉴定与次苄基阳离子配对的手性反离子，以优异的对映选择性参与催化不对称CC、CO和CN键形成反应。关键阳离子中间体可以通过路易斯酸或布氏酸催化从不同的前体获得。该策略的关键是只使用弱碱性、受限的反离子，这些反离子被认为可以延长碳正离子的寿命，从而避免通往相应苯乙烯的非生产性去质子化途径。

附：英文原文

Title: Taming secondary benzylic cations in catalytic asymmetric SN1 reactions

Author: Vikas Kumar Singh, Chendan Zhu, Chandra Kanta De, Markus Leutzsch, Lorenzo Baldinelli, Raja Mitra, Giovanni Bistoni, Benjamin List

Issue&Volume: 2023-10-20

Abstract: 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 (SN1) 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 CC, CO, and CN bond-forming reactions with excellent enantioselectivity. The critical cationic intermediate can be accessed from different precursors via Lewis- or Brnsted 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.

DOI: adj7007

Source: https://www.science.org/doi/10.1126/science.adj7007