Synthesis of Neocannabinoids Using Controlled Friedel-Crafts Reactions

A simple, one-step transformation to produce 8,9-dihydrocannabidiol (H2CBD) and related “neocannabinoids” via controlled Friedel-Crafts reactions is reported. Experimental and computational studies probing the mechanism of neocannabinoid synthesis from cyclic allylic alcohol and substituted resorcinol reaction partners provide understanding of the kinetic and thermody-namic factors driving regioselectivity for the reaction. Herein, we present a reaction scope for neocannabinoid synthesis including the production of both normal and abnormal isomers under both kinetic and thermodynamic control. Discovery and optimization of this one-step protocol between various allylic alcohols and resorcinol derivatives is discussed and supported with density-functional theory (DFT) calculations.