HIGHLIGHT Cyclic Hypervalent Iodine Reagents and Iron Catalysis: the Winning Team for Late-Stage C-H Azidation

In the past decades azides have received increasing attention due to their exceptional reactivity and versatility in organic chemistry. Their use as non-basic precursors of amines or their easy conversion to nitrene intermediates for further C-N bond transformations made them key building blocks in chemistry, biology and material science. In spite of their hailed synthetic utility, their installation into organic molecules traditionally proceeds via substitution reactions, which usually require the pre-functionalization of the substrate. Methods allowing the selective introduction of azides into C-H bonds at a late-stage of the synthesis would represent a breakthrough in the field by giving a more efficient entry to these versatile building blocks. Recently, Sharma and Hartwig reported a practical methodology in which the challenges of reactivity and selectivity represented by the late stage azidation of C-H bonds were successfully overcome by the combination of an azidobenziodoxolone reagent and an iron catalyst. The envisaged azidation reaction requires a reactive, yet stable azide precursor, which is tolerant to functional groups and can at the same time act as a mild oxidant to perform C-H functionalization. In this context, hypervalent iodine reagents appear as excellent candidates, as they display several of the desired properties. They had been indeed applied to azide transfer since a long time, but the available reagents were highly unstable at room temperature. In 1994, Zhdankin and coworkers, shortly followed by Kita and co-workers, reported the first examples of cyclic and bench-stable azidobenziodoxol(on)e reagents 1-3 (Figure 1).