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.
Avery
Thomas D
TD
Department of Chemistry, The University of Adelaide, South Australia 5005, Australia.
Greatrex
Ben W
BW
Pedersen
Daniel Sejer
DS
Taylor
Dennis K
DK
Tiekink
Edward R T
ER
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000737:chemistry; D004146:Dioxanes / Q000737:chemistry*; D008968:Molecular Conformation; D009943:Organophosphorus Compounds / Q000737:chemistry*; D013237:Stereoisomerism
D000596:Amino Acids; D003521:Cyclopropanes; D004146:Dioxanes; D009943:Organophosphorus Compounds