We have described simple, high-yield, protocols, requiring only commonly accessible equipment, to synthesize a wide range of β-CD derivatives mono-substituted at the secondary face. Steric hindrance, a key obstacle to functionalizing the secondary face of β-CD, was circumvented by the use of linear nucleophiles and less bulky coupling agents; by using a skinny linker, such as glycine and amic acids, to position bulkier reactants away from the bulk of the host molecule; and by using β-amino acids, instead of α-amino acids, to position bulky side chains slightly further from the secondary rim. Some reactions were also enhanced by inclusion of adamantane, an inert component of the reaction mixture that presumably helps by displacing reactants from the binding cavity. The synthetic approaches described here open new possibilities for the use of modified β-CDs in applications that include testing and improvement of simulation force fields, enhanced pharmaceutical formulations, and novel supramolecular constructs and devices.