Chiral Bis‐phosphate Macrocycles for Catalytic, Efficient, and Enantioselective Electrophilic Fluorination

• Published in: Chemistry : a European journal 2024-04, Vol.30 (24), p.e202400498-n/a
• Main Authors: Zhang, Lie‐Wei, Wang, Xu‐Dong, Ao, Yu‐Fei, Wang, De‐Xian, Wang, Qi‐Qiang
• Format: Article
• Language: English
• Subjects: Binding; Catalysis; Catalysts; Chemical synthesis; chiral macrocycles; Cooperation; Crystallography; electrophilic fluorination; Enantiomers; Fluorination; ion-pair interactions; Reagents; Selectfluor; supramolecular catalysis; Tryptamines
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202400498

Incorporation of privileged catalytic scaffolds into a macrocyclic skeleton represents an attractive strategy to furnish supramolecular catalysis systems with enzyme‐mimetic cavity and multi‐site cooperation. Herein we reported the synthesis, structure, binding properties and catalytic application of a series of chiral bis‐phosphate macrocycles toward the challenging asymmetric electrophilic fluorination. With a large, integrated chiral cavity and two cooperative phosphate sites, these macrocycles exhibited good inclusion toward 1,4‐diazabicyclo[2.2.2]octane (DABCO) dicationic ammoniums through complementary ion‐pair and C−H⋅⋅⋅O interactions, as confirmed by crystallographic and solution binding studies. In fluorocyclization of tryptamines with Selectfluor reagent which has a similar DABCO‐based dicationic structure, only 2 mol% macrocycle catalyst afforded the desired pyrroloindoline products in moderate yields and up to 91 % ee. For comparison, the acyclic mono‐phosphate analogue gave obviously lower reactivity and enantioselectivity (