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 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%. © 2002 Wiley-Liss, Inc.