Synthesis of neocannabinoids using controlled friedel-crafts reactions

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2023-Millimcai et al.pdf(1.9 MB)
Accepted manuscript
Date
2023-09-15
Authors
Millimaci, Alexandra M.
Trilles, Richard V.
McNeely, James H.
Brown, Lauren E.
Beeler, Aaron B.
Porco, John A.
Version
Accepted manuscript
OA Version
Citation
A.M. Millimaci, R.V. Trilles, J.H. McNeely, L.E. Brown, A.B. Beeler, J.A. Porco. 2023. "Synthesis of Neocannabinoids Using Controlled Friedel-Crafts Reactions." Journal of Organic Chemistry, Volume 88, Issue 18, pp.13135-13141. https://doi.org/10.1021/acs.joc.3c01362
Abstract
A 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 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.
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