A concise route to beta-Cyclopropyl amino acids utilizing 1,2-dioxines and stabilized phosphonate nucleophiles.

1,2-Dioxines react with glycine-derived phosphonate nucleophiles via a multistep cascade reaction to give beta-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 beta-cyclopropyl amino acids that are selective and potent agonists or antagonists of the metabotropic glutamate receptors in excellent yields.