title: Asymmetric Pentafulvene Carbometalation--Access to Enantiopure Titanocene Dichlorides of Biological Relevance.
abstract: Unprecedented asymmetric copper-catalyzed addition of ZnEt2 (ZnBu2) to the exocyclic C=C bond of pentafulvenes C5H4(=CHAr) (Ar=2-MeOPh and related species) results in enantiomerically enriched (up to 93:7 e.r.) cyclopentadienyl ligands (C5H4CHEtAr; abbreviated Cp(R)). Copper catalyst promotion with both chiral phosphoramidite ligands and a phosphate additive is vital in realizing both acceptable enantioselectivities and reaction rates. Enantiomeric Cp(R)2TiCl2 complexes have been prepared; the (S,S) isomer is twice as active towards pancreatic, breast, and colon cancer cell lines as its (R,R) enantiomer at 24 h.
authors.affiliation: School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD (UK). cinimelchior@gmail.com.|School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham NG7 2RD (UK). cinimelchior@gmail.com.
authors.forename: Melchior
authors.initials: M
authors.lastname: Cini
authors.affiliation: School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham NG7 2RD (UK). tracey.bradshaw@nottingham.ac.uk.
authors.forename: Tracey D
authors.initials: TD
authors.lastname: Bradshaw
authors.affiliation: School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD (UK). simon.woodward@nottingham.ac.uk.
authors.forename: Simon
authors.initials: S
authors.lastname: Woodward
authors.affiliation: School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD (UK).
authors.forename: William
authors.initials: W
authors.lastname: Lewis
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002384:Catalysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003300:Copper / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D003300:Copper; C020528:titanocene dichloride
keywords: CC coupling; asymmetric catalysis; carbometalation; copper; ligand effects