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

作者：Lie‐Wei Zhang, Wang Xu-dong, Yu‐Fei Ao, De‐Xian Wang, Qi‐Qiang Wang · 发表于：Chemistry - A European Journal · 年份：2024 · DOI：10.1002/chem.202400498 · 被引用次数：11 · 研究领域：Fluorine in Organic Chemistry、Porphyrin and Phthalocyanine Chemistry、Chemical Synthesis and Analysis

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 (<20 % ee), suggesting a remarkable macrocyclic effect. The high catalytic efficiency and superior stereocontrol were ascribed to the tight ion-pair binding and cavity-directed noncovalent interaction cooperation.