Taming secondary benzylic cations in catalytic asymmetric SN1 reactions

• 成果类型: Article
• 署名作者: Singh, Vikas Kumar; Zhu, Chendan; De, Chandra Kanta; Leutzsch, Markus; Baldinelli, Lorenzo; Mitra, Raja; Bistoni, Giovanni; List, Benjamin
• 署名单位: Max Planck Society; University of Perugia; Indian Institute of Technology System (IIT System); Indian Institute of Technology (IIT) Goa
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8587
• DOI: 10.1126/science.adj7007
• 发表日期: 2023-10-20
• 页码: 325-329
• 关键词: dynamic kinetic resolution; alcohols; electrophilicity; TRANSFORMATION; hydrolysis; alkylation; amination; oxidation; efficient; olefins

摘要

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 (S(N)1) 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 BrOnsted 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.