Catalyst-free synthesis of hydrazino-containing glycine derivatives via a diaziridine in situ formation/ring-opening cascade†

Abstract

Glycine derivatives are prevalent structural motifs that can be easily found in many bioactive molecules and natural isolates. To date, chemical synthesis of hydrazino-containing glycine derivatives has mainly focused on the utilization of metal catalysts or light-irradiation methods. Herein, we report a three-component reaction of amines, azodicarboxylates, and diazoalkanes under green and sustainable reaction conditions, leading to a wide range of hydrazino-containing glycine derivatives in good to excellent yields. Compared to the reported methods, the as-developed method does not require catalysts or light irradiation. The success of the scale-up reaction, synthetic transformation of the formed glycine products, and the direct aqueous media synthesis further rendered the method attractive and valuable. Control experiments together with detailed mechanism studies revealed that the in situ formed diaziridines are the key reaction intermediates.