Radical Azidation/Cyclization Cascade of <i>N</i> -Acrylohydrazides: Access to Biologically Relevant Azido-Pyrazolones

A metal-free sustainable method was developed for the construction of pharmaceutically important azido-pyrazolones via a radical azidation/5<i>-endo-trig</i> cyclization cascade of <i>N</i>-acrylohydrazides. The protocol exhibits a broad substrate scope and good to excellent yields of products. Furthermore, the use of readily available, inexpensive, and nontoxic materials, mild reaction conditions, tolerance to air and moisture, and operational simplicity make this strategy highly attractive. Gram-scale synthesis and further transformation of products, including the conjugation of drug molecules and amino acids were demonstrated to show the practicality and utility of this environmentally friendly method. Mechanistic studies reveal that hypervalent iodine(III) reagent promotes the formation of azide radicals from trimethylsilyl azide for subsequent addition/cyclization cascade.