Synthesis of cyclopropanes via organoiron methodology: stereoselective preparation of cis-2-(2′-carboxycyclopropyl)glycine

Abstract

A stereoselective route to cis-2-(2′-carboxycyclopropyl)glycine has been developed. exo-Nucleophilic addition to the (bicyclo[5.1.0]octadienyl)iron(1+) cation establishes the relative stereochemistry at the cyclopropane ring and the α-stereocenter. Subsequent removal of the metal and cleavage of the cyclic diene gave the protected target 10, which upon hydrolysis gave 1. A stereoselective route to cis-2-(2′-carboxycyclopropyl)glycine has been developed. exo-Nucleophilic addition to the (bicyclo[5.1.0]octadienyl)iron(1+) cation establishes the relative stereochemistry at the cyclopropane ring and the α-stereocenter.

Reactivity of (Bicyclo[5.1.0]octadienyl)iron(1+) Cations: Application to the Synthesis of cis-2-(2‘-Carboxycyclopropyl)glycines

“…Synthesis of ( ± )- cis -2-(2 ‘ -Carboxycyclopropyl)glycine. L -Glutamic acid (Chart ) is the major excitatory neurotransmitter for a wide variety of receptors in mammalian systems . The selective activation of different glutamate receptors may depend on recognition of a particular conformer of this flexible molecule.…”

Natural Occurrence, Syntheses, and Applications of Cyclopropyl-Group-Containing α-Amino Acids. 2. 3,4- and 4,5-Methanoamino Acids

“…Subsequent twofold glycol cleavage, Jones oxidation, and esterification afforded the protected cis-(2-carboxycyclopropyl)glycine 139, which could be deprotected to the free amino acid cis-127 (Scheme 19). 88 An asymmetric variant of this methodology using an iron complex analogous to 135, but endowed with a chiral (-)neomenthyldiphenylphosphine instead of the triphenylphosphine ligand, was tested; however, the enantiomeric excess in the final product cis-127 was only 38%. 89 L-Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS), acting through either ligand-gated ion channels, the ionotropic receptors (subclasses: N-methyl-D-aspartate NMDA, kainate KA, and R-amino-5-hydroxy-3-methyl-4-isoxazole propionic acid AMPA), or G-protein coupled, metabotropic receptors (subclasses: group I with mGluR 1 and 5, group II with mGluR 2 and 3, and group III with mGluR 4, 6, 7, and 8).…”

“…Reaction of 136 with potassium phthalimide gave the phthalimido-substituted complex 137 , from which the ligand was liberated by oxidation with ceric ammonium nitrate and further hydroxylated with osmium tetroxide to furnish the tetrol 138 as a mixture of two unidentified diastereomers. Subsequent twofold glycol cleavage, Jones oxidation, and esterification afforded the protected cis -(2-carboxycyclopropyl)glycine 139 , which could be deprotected to the free amino acid cis - 127 (Scheme ) …”