title: Enantioselective carbon-hydrogen insertion is an effective and efficient methodology for the synthesis of (R)-(-)-baclofen.
abstract: A highly enantioselective methodology for the synthesis of the GABA(B) receptor agonist (R)-(-)-baclofen is described. This synthesis begins with p-chlorophenethyl alcohol and involves a catalytic carbon-hydrogen insertion reaction of a chiral dirhodium(II) carboxamidate with the corresponding diazoacetate (81% yield, 95% ee). Subsequent steps convert the intermediate gamma-lactone to (R)- (-)-baclofen in a 60% overall yield. The amount of catalyst required for the C-H insertion transformation is only 0.5 mol%.
authors.affiliation: Department of Chemistry, University of Arizona, Tucson, Arizona, USA. mdoyle@u.arizona.edu
authors.forename: Michael P
authors.initials: MP
authors.lastname: Doyle
authors.forename: Wenhao
authors.initials: W
authors.lastname: Hu
mesh_terms: D001418:Baclofen / Q000138:chemical synthesis* / Q000737:chemistry; D002244:Carbon; D002384:Catalysis; D006859:Hydrogen; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013237:Stereoisomerism
chemical_list: D007202:Indicators and Reagents; D002244:Carbon; D006859:Hydrogen; D001418:Baclofen