Enantioselective carbon‐‐hydrogen insertion is an effective and efficient methodology for the synthesis of (r)‐(‐)‐baclofen
- 1 January 2002
- Vol. 14 (2-3) , 169-172
- https://doi.org/10.1002/chir.10060
Abstract
A highly enantioselective methodology for the synthesis of the GABAB 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 γ-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%. Chirality 14:169–172, 2002.Keywords
This publication has 15 references indexed in Scilit:
- Michael addition of nitromethane to non-racemic chiral Cr(CO)3 complexes of ethyl cinnamate derivatives: stereoselective synthesis of (R)-(−)-baclofenTetrahedron: Asymmetry, 2000
- Enantioselective synthesis of (R)-(−)-baclofen using Fischer-type carbene anionsTetrahedron: Asymmetry, 2000
- An efficient synthesis of (R)-(−)-baclofenTetrahedron: Asymmetry, 1999
- Enantioselective synthesis of β-substituted butyric acid derivatives via orthoester Claisen rearrangement of enzymatically resolved allylic alcohols: application to the synthesis of (R)-(−)-baclofenTetrahedron: Asymmetry, 1997
- Intramolecular Regioselective Insertion into Unactivated Prochiral Carbon−Hydrogen Bonds with Diazoacetates of Primary Alcohols Catalyzed by Chiral Dirhodium(II) Carboxamidates. Highly Enantioselective Total Synthesis of Natural Lignan LactonesThe Journal of Organic Chemistry, 1996
- A Practical Synthesis of (2S, 3R)‐3‐Amino‐2‐methylpentanoic Acid from L‐Aspartic AcidHelvetica Chimica Acta, 1994
- 3-amino-2-(4-chlorophenyl)-nitropropane is a new GABAB receptor agonist, more active peripherallyEuropean Journal of Pharmacology, 1993
- Asymmetric synthesis of lactones with high enantioselectivity by intramolecular carbon-hydrogen insertion reactions of alkyl diazoacetates catalyzed by chiral rhodium(II) carboxamidesJournal of the American Chemical Society, 1991
- 3-Thienyl- and 3-furylaminobutyric acids. Synthesis and binding GABAB receptor studiesJournal of Medicinal Chemistry, 1991
- The biological activity of d-baclofen (Lipresal®)European Journal of Pharmacology, 1978