A Metal-Free Cycloaddition of α-Diazoacetates with Amino Acid-Derived NHPI Esters for the Facile Synthesis of 1,2,4-Triazoles.

Abstract

1,2,4-Triazoles are privileged scaffolds for many pharmaceuticals, and methods for structurally diverse compound libraries are of current interest. Here we report an efficient coupling of α-diazoacetates with amino acid-derived alkyl N-hydroxy phthalimide esters, under metal-free conditions involving 1,8-diazabicyclo(5.4.0)undec-7-ene as the base, with which highly functionalized 1,2,4-triazoles can be obtained in excellent yields with remarkable functional group tolerance. Preliminary studies revealed that 1,2,4-triazole 3a exhibits potent inhibition of tyrosinase activities in melanoma B16F10 cell lines, demonstrating promising skin-whitening properties.