The electrophilic zwitterionic ring expansion polymerization of monosubstituted epoxides initiated by tris-(pentafluorophenyl)borane [B(C6F5)(3)] is investigated to reveal the effect of substituents on the generation of functional macrocyclic polyethers and to understand the formation of topological impurities for better control of architectural purity during polymerization. With this aim, different families of monofunctional epoxides were polymerized, and the products were analyzed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-ToFMS). The data revealed that side reactions coexist with the macrocyclization reaction, including chain transfer reactions to the monomer. With the detailed MALDI-ToF MS analysis, it was possible to ascertain structural assignments of major and minor products and propose corresponding reaction mechanisms. Substituent effects were also studied to probe the functional group tolerance of this polymerization. Finally, computational studies were performed to examine the chemical interaction between the monomer and B(C6F5)(3) catalyst, which corroborated the experimental results by providing insight into the likelihood of generating noncyclic byproducts. By using both analytical and computational tools, the polymerization could be optimized to generate macrocyclic polyethers with substantially increased purity.