Pathway Engineering in Pd‐Based Supramolecular Cage Synthesis via Inner‐Outer Steric Synergy

For artificial supramolecular architectures designed to mimic biological systems, achieving different pathway synthesis is challenging due to the requirement of multiple stable and interconvertible intermediates. Here, we propose a novel "inner-outer steric synergy" strategy and investigate controllable pathway engineering for the synthesis of specific structures. Firstly, three structures (Ring-Pd₂L^A ₂, Bowl-Pd₂L^A ₃ and Cage-Pd₂L^A ₄) with interconversion properties were selectively formed by assembling externally modified ligand L^A with Pd(II). Furthermore, Ring-Pd₂L^A ₂ can further assemble with the ligand L^B with inner steric hindrance to generate heteroleptic trans-Pd₂L^A ₂L^B ₂ cage, while Bowl-Pd₂L^A ₃, as an intermediate, can assemble with L^B to form Pd₂L^A ₃L^B. It is noteworthy that Ring-Pd₂L^A ₂, Bowl-Pd₂L^A ₃, and Cage-Pd₂L^A ₄ can interconvert under specific conditions, enabling the synthesis of Pd₂L^A ₃L^B and trans-Pd₂L^A ₂L^B ₂ through 10 and 16 pathways, respectively. This research not only introduces a novel strategy for constructing heteroleptic cages but also demonstrates the achievement of pathway engineering.