A Revised Modular Approach to (-)- trans-Δ8-THC and Derivatives Through Late-Stage Suzuki-Miyaura Cross-Coupling Reactions

Victor R L J Bloemendal; Daan Sondag; Hidde Elferink; Thomas J Boltje; Jan C M van Hest; Floris P J T Rutjes

doi:10.1002/ejoc.201900059

A Revised Modular Approach to (-)- trans-Δ⁸-THC and Derivatives Through Late-Stage Suzuki-Miyaura Cross-Coupling Reactions

European J Org Chem. 2019 Mar 31;2019(12):2289-2296. doi: 10.1002/ejoc.201900059. Epub 2019 Mar 18.

Authors

Victor R L J Bloemendal¹, Daan Sondag¹, Hidde Elferink¹, Thomas J Boltje¹, Jan C M van Hest², Floris P J T Rutjes¹

Affiliations

¹ Institute for Molecules and Materials Heyendaalseweg 135 NL-6525 AJ Nijmegen The Netherlands.
² Eindhoven University of Technology P.O. Box 513 (STO 3.31) NL-5600 MB Eindhoven The Netherlands.

Abstract

A revised modular approach to various synthetic (-)-trans-Δ⁸-THC derivatives through late-stage Suzuki-Miyaura cross-coupling reactions is disclosed. Ten derivatives were synthesized allowing both sp²- and sp³-hybridized cross-coupling partners with minimal β-hydride elimination. Importantly, we demonstrate that a para-bromo-substituted THC scaffold for Suzuki-Miyaura cross-coupling reactions has been initially reported incorrectly in recent literature.

Keywords: Cannabis derivatives; Cascade reactions; Heterocycles; Suzuki–Miyaura coupling; Tetrahydrocannabinol.