title: Stereolability of chiral ruthenium catalysts with frozen NHC ligand conformations investigated by dynamic-HPLC.
abstract: The stereolability of chiral Hoveyda-Grubbs II type ruthenium complexes bearing N-heterocyclic carbene (NHC) ligands with Syn-phenyl groups on the backbone and Syn- or Anti-oriented o-tolyl N-substituents was studied by resorting to dynamic high-performance liquid chromatography (D-HPLC). A complete chromatographic picture of the involved stereoisomers (four for Anti- and two for Syn-complexes) was achieved at very low temperatures (-53°C and -40°C respectively), at which the NHC-Ru bond rotations were frozen out. Inspection of the chromatographic profiles recorded at higher temperatures revealed the presence of plateau zones between the couples of either Syn or Anti stereoisomers, attesting to the active interconversion between the eluted species. Such dynamic chromatograms were successfully simulated through procedures based on both theoretical plate and classical stochastic models. The good superimposition achieved between experimental and simulated chromatographic profiles allowed determination of the related isomerization energy barriers (ΔGisom (#) ), all derived by rotation around the NHC-Ru bond. The obtained diastereomerization barriers between the Anti isomers were found in very good agreement with those previously measured by experimental nuclear magnetic resonance (NMR) and assessed through Density Functional Theory (DFT) calculations. With the same approach, for the first time we also determined the enantiomerization barrier of the Syn isomer. Focused changes to the structure of complex Syn, studied by a molecular modeling approach, were found suitable to strongly reduce the stereolability arising from rotation around the NHC-Ru bond.
authors.affiliation: Department of Chemistry and Technology of Drug, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Menta
authors.affiliation: Department of Chemistry and Technology of Drug, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Pierini
authors.affiliation: Department of Drug, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cirilli
authors.affiliation: Department of Chemistry and Biology, University of Salerno, Salerno, Italy.
authors.forename: Fabia
authors.initials: F
authors.lastname: Grisi
authors.affiliation: Department of Chemistry and Biology, University of Salerno, Salerno, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Perfetto
authors.affiliation: Department of Chemistry and Technology of Drug, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Ciogli
mesh_terms: D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006571:Heterocyclic Compounds / Q000737:chemistry*; D007700:Kinetics; D008024:Ligands; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D006571:Heterocyclic Compounds; D008024:Ligands; D009942:Organometallic Compounds; C030011:carbene; D012428:Ruthenium; D008697:Methane
keywords: Chiralpak IA; activation energy barrier; atropisomers; dynamic-high-performance liquid chromatography; ruthenium complexes