biostudies-literatureMillimaci AMNational Institute of General Medical SciencesCBDQure IncNIGMS NIH HHS13135-13141https://www.ebi.ac.uk/biostudies/studies/S-EPMC10696561biostudies-literatureUnknown88(18)A one-step transformation to produce 8,9-dihydrocannabidiol (H₂CBD) and related "neocannabinoids" <i>via</i> 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 thermodynamic factors driving regioselectivity for the reaction. Herein, we present the 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 are discussed and supported with density functional theory calculations.The Journal of organic chemistrySynthesis of Neocannabinoids Using Controlled Friedel-Crafts Reactions.PMC10696561R35 GM118173GM 118173Trilles RVBeeler ABMillimaci AMMcNeely JHPorco JABrown LEfalseSynthesis of Neocannabinoids Using Controlled Friedel-Crafts Reactions.A one-step transformation to produce 8,9-dihydrocannabidiol (H₂CBD) and related "neocannabinoids" <i>via</i> 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 thermodynamic factors driving regioselectivity for the reaction. Herein, we present the 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 are discussed and supported with density functional theory calculations.2023-01-01T00:00:00Z2023 Sep2025-04-22T07:59:59.827Z2025-04-05T22:24:09.379ZS-EPMC106965613765712210.1021/acs.joc.3c01362