A Concise Route to β-Cyclopropyl Amino Acids Utilizing 1,2-Dioxines and Stabilized Phosphonate Nucleophiles

Abstract

1,2-Dioxines react with glycine-derived phosphonate nucleophiles via a multistep cascade reaction to give β-cyclopropyl amino acid derivatives in good yield with excellent control of the cyclopropane stereocentres. The cyclopropyl ketones were oxidized to the corresponding carboxylic esters using Baeyer−Villiger conditions. Standard deprotection protocols produced a series of known β-cyclopropyl amino acids that are selective and potent agonists or antagonists of the metabotropic glutamate receptors in excellent yields.