AbstractA combined computational and structural study of the lithium affinity (LA) of O—C—O systems exhibiting the anomeric effect and of O— C—C—O systems exhibiting the gauche effect is presented. QM ab initio calculations using the MP2/6–31G* basis set were carried out on the gas‐phase lithium affinities of dimethoxymethane (DMOM), dimethoxyethane (DMOE), 1,3‐dioxane (DOX) and cis‐ and trans‐tetraoxadecalin (TOD), along with that of dimethyl ether and of its dimer as reference compounds. Structural parameters were retrieved from the Cambridge Structural Database (CSD) for diethyl ether dimer and O—C—C—O lithium complexes and these agreed well with the calculated data. The computed lithium affinities of dimethoxymethane and dimethoxyethane were found to be conformationally dependent. The LAs are conformationally dependent (wherever applicable) and decrease in the order: (Me2O)2 > DMOE > DMOM > DOD > DOX > trans‐TOD, but cis‐TOD restores the high LA (better than DMOE) by virtue of multiple coordination. Copyright © 2001 John Wiley & Sons, Ltd.