title: Atropisomerism about aryl-Csp(3) bonds: the electronic and steric influence of ortho-substituents on conformational exchange in cannabidiol and linderatin derivatives.
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-Csp(3) 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(sp(2))-C(sp(3)) single bonds through theoretical calculations.
authors.affiliation: ICMR, CNRS UMR 7312, Faculté de Pharmacie, Université de Reims Champagne-Ardenne , 51 rue Cognacq-Jay, F-51096 Reims Cedex, France.
authors.forename: Hatice
authors.initials: H
authors.lastname: Berber
authors.forename: Pedro
authors.initials: P
authors.lastname: Lameiras
authors.forename: Clément
authors.initials: C
authors.lastname: Denhez
authors.forename: Cyril
authors.initials: C
authors.lastname: Antheaume
authors.forename: Jonathan
authors.initials: J
authors.lastname: Clayden
mesh_terms: D002185:Cannabidiol / Q000031:analogs & derivatives* / Q000737:chemistry*; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010636:Phenols; D011789:Quantum Theory; D013237:Stereoisomerism
chemical_list: D010636:Phenols; C000593322:linderatin; D002185:Cannabidiol