Atropisomerism about aryl-csp3 bonds: The electronic and steric influence of ortho -substituents on conformational exchange in cannabidiol and linderatin derivatives

Hatice Berber*, Pedro Lameiras, Clément Denhez, Cyril Antheaume, Jonathan Clayden

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

12 Citations (Scopus)

Abstract

Terpenylation reactions of substituted phenols were used to prepare cannabidiol and linderatin derivatives, and their structure and conformational behavior in solution were investigated by NMR and, for some representative examples, by DFT. VT-NMR spectra and DFT calculations were used to determine the activation energies of the conformational change arising from restricted rotation about the aryl-Csp3 bond that lead to two unequally populated rotameric epimers. The NBO calculation was applied to explain the electronic stabilization of one conformer over another by donor-acceptor charge transfer interactions. Conformational control arises from a combination of stereoelectronic and steric effects between substituents in close contact with each other on the two rings of the endocyclic epoxide atropisomers. This study represents the first exploration of the stereoelectronic origins of atropisomerism around C(sp2)-C(sp3) single bonds through theoretical calculations.

Original languageEnglish
Pages (from-to)6015-6027
Number of pages13
JournalJournal of Organic Chemistry
Volume79
Issue number13
Early online date23 Jun 2014
DOIs
Publication statusPublished - 3 Jul 2014

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