Unveiling the Origin of Regioselectivity in Iron(III)-Promoted Friedel–Crafts Synthesis of Cannabinoids: Theoretical Studies and Synthetic Applications
O-catalyzed reaction that enables diastereoselective and highly regioselective preparation of (-)-CBD under mild and scalable conditions. Here, we report experimental and computational mechanistic studies that provide insight into the origin of this regioselectivity and support the involvement of a catalytically relevant iron(III)-olivetol complex, which reacts regioselectively with the carbocation generated from the terpenic unit. We also define the scope and limitations of the method and demonstrate its synthetic utility through the efficient formal synthesis of bioactive cannabinoid derivatives, including HU-210 and ajulemic acid.
Authors
- Antonio Sánchez‐Ruiz (ORCID: https://orcid.org/0000-0002-3656-7442)
- Francisco Sarabia (ORCID: https://orcid.org/0000-0002-5149-3576)
- Juan Manuel López‐Romero (ORCID: https://orcid.org/0000-0003-2422-655X)
- Iván Cheng‐Sánchez (ORCID: https://orcid.org/0000-0001-8606-6710)
- Juan Suárez
- Irama Fuentes-Pino
- Mohamed El Hllafi
- Mohamed Amin El Amrani
Institutions
- Abdelmalek Essaâdi University (MA)
- Biotechnology Research Center (IR)
- Institute of Microbiology and Biotechnology (MD)
- Institute for Legal Studies (HU)
- Instituto de Investigación Biomédica de Málaga (ES)
- Universidad de Málaga (ES)
Publication Details
- Journal
- The Journal of Organic Chemistry
- Published
- 2026-07-23
- DOI
- https://doi.org/10.1021/acs.joc.6c01142
- Primary Topic
- Asymmetric Hydrogenation and Catalysis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Ministerio de Ciencia, Innovación y Universidades