title: High-Performance Liquid Chromatographic Resolution of Neutral and Cationic Hetero[6]Helicenes.
abstract: Cationic hetero[6]helicenes 1+, 2+ and 3+ have been recently disclosed. Herein we report on their enantiomeric separation using high-performance liquid chromatography. Separation of the antipodes can be achieved in preparative scale on neutral adducts with Chiralcel OD-I or Chiralpak ID CSP. Selectivity factors of 1.90, 1.67, and 1.96 were obtained for 1-H, 2-H, and 3-H, respectively. Separation can also be performed on the carbenium ions on regular Chiralpak IA CSP using water-containing eluents, thus allowing for enantiomeric purity determinations in aqueous environments. Resolution of neutral and cationic helicenes is also achieved on more recently developed LARIHC columns. The versatility of the cyclofructan phases allows for baseline separations for both cases and their loading capabilities are demonstrated. Finally, the configurational stability of 1+, 2+, and 3+ was measured. For each replacement of an oxygen atom by an amino group, the racemization barrier increases significantly (ΔG‡ = 29.8, 36.3 and >37 kcal mol(-1) for 1+, 2+, and 3+ respectively).
authors.affiliation: Department of Organic Chemistry, University of Geneva, Geneva, Switzerland.
authors.forename: Geraldine M
authors.initials: GM
authors.lastname: Labrador
authors.affiliation: Department of Organic Chemistry, University of Geneva, Geneva, Switzerland.
authors.forename: Johann
authors.initials: J
authors.lastname: Bosson
authors.affiliation: Department of Chemistry and Biochemistry, University of Texas at Arlington, Arlington, Texas, USA.
authors.forename: Zachary S
authors.initials: ZS
authors.lastname: Breitbach
authors.affiliation: Department of Chemistry and Biochemistry, University of Texas at Arlington, Arlington, Texas, USA.
authors.forename: Yeeun
authors.initials: Y
authors.lastname: Lim
authors.affiliation: Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Francotte
authors.affiliation: Department of Drug Chemistry and Technologies, University of Rome La Sapienza, Rome, Italy.
authors.forename: Rocchina
authors.initials: R
authors.lastname: Sabia
authors.affiliation: Department of Drug Chemistry and Technologies, University of Rome La Sapienza, Rome, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Villani
authors.affiliation: Department of Chemistry and Biochemistry, University of Texas at Arlington, Arlington, Texas, USA.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Armstrong
authors.affiliation: Department of Organic Chemistry, University of Geneva, Geneva, Switzerland.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Lacour
mesh_terms: D000588:Amines / Q000737:chemistry*; D002412:Cations / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D006571:Heterocyclic Compounds / Q000737:chemistry*; D011083:Polycyclic Compounds / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000588:Amines; D002412:Cations; D006571:Heterocyclic Compounds; D011083:Polycyclic Compounds; C031660:helicenes
keywords: CSP-HPLC resolution; carbenium ions; helical conformations; racemization barriers; single enantiomers