Iron-catalysed intramolecular C(sp3)–H amination of alkyl azides

Abstract

Iron-catalysed intramolecular C(sp³)–H amination of alkyl azides (N₃R, R = alkyl) via the iron–alkylnitrene/alkylimido (Fe(NR)) intermediate, is an appealing synthetic approach for the synthesis of various N-heterocycles. This approach provides a direct atom-economy strategy for constructing C(sp³)–N bonds, with nitrogen gas as the only by-product and iron is a biocompatible, cheap, and earth-abundant metal. However, C(sp³)–H amination with alkyl azides is challenging because alkyl nitrenes readily undergo 1,2-hydride migration to imines. This article summarizes recent major advances in this field in terms of catalyst design, substrate scope expansion, stereoselectivity control, understanding of key reaction intermediates, and applications in the synthesis of complex natural products and pharmaceuticals.