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

Abstract

AbstractIncorporation 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.