Synthesis of a Cannabidiol Precursor: Experimental Challenges and DFT Insights into β‑Elimination Barriers

Abstract The synthesis of cannabidiol (CBD) from limonene derivatives involves a key β-elimination step that remains challenging to reproduce efficiently. In this work, we revisited a known racemic synthetic route to CBD and investigated the mechanistic origin of the low yield associated with the β-hydrogen elimination step. Alternative synthetic approaches were tested experimentally by comparing the traditional selenoxide-mediated pathway with a direct elimination attempt from bromohydrin intermediates. Despite optimization of reaction and workup conditions, β-elimination consistently failed, regenerating epoxide 1