Liquid and solid phase syntheses of orthogonally protected α-hydrazinoacid derivatives

Abstract

The first solid phase synthesis of chiral α-hydrazinoacids has been developed. This synthesis was achieved by the preparation of solid supported- N-alkyloxycarbonyl-aminophthalimides used as acidic partners in the Mitsunobu protocol involving α-hydroxyesters. Two different final trans-protection steps of the phthaloyl group, developed first in liquid phase, result in efficient releases of orthogonally bis-protected or fully tris-protected hydrazine derivatives. A comparison between liquid and solid phase syntheses is outlined: even if the overall yields are sometimes rather higher by the liquid phase synthesis, the on-resin protocol is much more rapid and convenient than the liquid protocol.