A family of chiral lower-rim substituted calixarene ligands 1–14 is synthesized and characterized as prospective ligands for synthesis of asymmetric active sites for heterogeneous catalysis and adsorption using a surface organometallic approach. The ligands possess asymmetric centers directly attached to lower-rim oxygens; the asymmetric centers are tailored with sterically bulky naphthyl and electron withdrawing CF₃ substituents. ¹H and ¹³C NMR spectroscopies demonstrate that mono- and 1,3-di-alkylated calixarenes synthesized using this procedure adopt the cone-shaped conformation, which is stabilized by multiple hydrogen bonds at the lower rim. Smaller pendant groups and polar solvents increase the dialkylation/monoalkylation ratio. The reaction proceeds with full inversion of configuration as established viasingle crystal X-ray diffraction of an N-Cbz-protected aminocyclopentoxy-modified calixarene. The calixarenes synthesized by this approach are characterized using circular dichroism (CD) spectroscopy and ab initio modeling, which is used to identify the minimal molecular fragment responsible for the observed lowest energy Cotton effect in the CD spectrum. Factors that influence the intramolecular induction of asymmetry throughout the calixarene scaffold are investigated by systematically varying substituent steric bulk, connectivity of the asymmetric center to the calixarene core, and the extent of hydrogen bonding at the calixarene lower rim. The asymmetry of the calixarene core is quantified using ¹H NMR spectroscopic shifts of aromatic meta and methylene bridge hydrogens and supported using ab initio calculations. The results demonstrate that calixarene core asymmetry is most strongly induced for rigid calixarene cores—an attribute that is expected to be preserved upon metal complexation and anchoring of these prospective ligands.