Efficient templated synthesis of pillar[6]arenes by in situ generated Lewis adducts

Abstract

Pillar[6]arenes exhibit highly valuable host-guest properties owing to their larger cavity relative to the widely studied pillar[5]arenes, yet their broader utilization has been impeded by longstanding challenges in selective and reproducible synthesis. Here, we report a general and efficient templated macrocyclization strategy based on the in situ formation of the Lewis adduct DABCO•2BF₃. The remarkable structural complementarity between this hexagonal template and the pillar[6]arene cavity, reinforced by strong CH-π interactions, drives highly selective formation of pillar[6]arenes under BF₃•Et₂O catalysis in common chlorinated solvents. Under optimized conditions, dodecaethoxy-pillar[6]arene P[6]OEt is obtained in up to 77% yield on gram scale, and the protocol can be readily scaled to multigram quantities without chromatography purification. The method is applicable to a range of monomers bearing saturated alkyl chains and provides straightforward access to the key precursor P[6]OH via dealkylation. Beyond its practical advantages, this work constitutes the first example of macrocyclization templated by a Lewis adduct. By overcoming critical limitations in selectivity, reproducibility, and scalability, this strategy offers an efficient solution for pillar[6]arene synthesis, opening new avenues for application developments.