Synthesis, Structural Characterization and Reactivity of Macrocyclic Cyclo[2]malonates

We report the controlled synthesis of a new class of oxygen-bridged cyclo[2]malonates via condensation of malonyl dichloride with substituted benzylic α,ω-diols. Optimization of reaction conditions enables selective access to dimeric macrocycles, overcoming the intrinsic tendency toward higher oligomer formation. Single-crystal X-ray diffraction reveals well-defined conformations, tunable cavity sizes, and substituent-dependent stereochemical preferences. The macrocycles assemble into interlocked columnar architectures driven by shape complementarity and stabilized by C−H···O hydrogen bonding, with additional halogen bonding in iodinated derivatives. While αproton acidity is retained across the series, vanadyl (VO2+) binding is strongly governed by cavity size and conformational preorganization, suggesting a structure−function relationship. These findings introduce cyclo[2]malonates as an accessible and versatile macrocyclic platform, combining structural tunability with predictable supramolecular behavior, and highlight their potential in molecular recognition and functional materials design.