Asymmetric Synthesis of (-)-Cannabidiol (CBD), (-)-Δ9-Tetrahydrocannabinol (Δ9-THC) and Their cis Analogs Using an Enantioselective Organocatalyzed Diels-Alder Reaction.
Yann Pauvert, André B. Charette
Organic Letters July 11, 2024 DOI: 10.1021/acs.orglett.4c01622 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Peer reviewed |
|---|---|
| Topics | Cannabis CBD |
| Key points | Reports an asymmetric synthesis of natural (-)-trans-CBD and psychoactive (-)-trans-Δ9-THC plus their cis diastereomers, using a prolinol-catalyzed enantioselective Diels-Alder reaction to build the cyclohexene carbaldehyde intermediate in good yield and high enantiomeric excess. Optimized resorcinol protecting groups avoid harsh, low-yield deprotection of the acid-sensitive resorcinol moiety. |
Abstract
Herein we describe an asymmetric synthesis of the pharmacologically relevant natural (-)-trans-CBD and psychoactive (-)-trans-Δ9-THC, as well as their synthetic cis diastereomers. The key step is an enantioselective Diels-Alder reaction catalyzed by a prolinol-based catalyst, which provides the cyclohexene carbaldehyde intermediate in good yield and high enantiomeric excess. Optimization of the substituted resorcinol protecting groups to avoid harsh and low-yield deprotection of the acid sensitive resorcinol moiety is also described.