We report herein a detailed investigation into the reaction mechanism for a sequential oxy-Cope/ene reaction under anionic conditions. With DFT calculations and ab initio molecular dynamics simulations, the observed diastereoselectivity is shown to be the result of an isomerization of the enolate olefin, which would evidently not occur under neutral conditions. The potential energy surface was thoroughly mapped out for the reaction pathways and the proposed mechanism confirmed the different product distributions observed under neutral and anionic oxy-Cope conditions. In addition, other possible pathways are shown to be higher in energy and experimental evidence is given that supports the olefin-isomerization pathway.