Synthesis of a sterically congested α,α'-iminodiacid

Article abstract of DOI:10.1016/S0040-4020(97)01065-X

The synthesis of iminodiacid 2, a derivative of valine, was found to be difficult at the point of attempting to functionalize the imino-nitrogen to form a tertiary amine. Nonetheless, a route was discovered starting from α-hydroxyisovaleric acid, ethanolamine and maleimide. After esterification, the α-triflate of α-hydroxyisovaleric acid was formed and used to sequentially alkylate the amino group of ethanolamine. Steric hindrance was reduced by tethering two of the amine substituents into lactone ring. This was followed by maleimide substitution of the hydroxyl group under Mitsunobu conditions.