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A radical cascade strategy for the modular synthesis of five-membered heteroarenes ( e.g. oxazoles, imidazoles) from feedstock reagents ( e.g. alcohols, amines, nitriles) has been developed. This double C–H oxidation is enabled by in situ generated imidate and acyloxy radicals, which afford regio- and chemo-selective β C–H bis-functionalization. The broad synthetic utility of this tandem hydrogen atom transfer (HAT) approach to access azoles is included, along with experiments and computations that provide insight into the selectivity and mechanism of both HAT events. 

The first catalytic strategy to harness imidate radicals for C–H functionalization has been developed. This iodine-catalyzed approach enables β C–H amination of alcohols by an imidate-mediated radical relay. In contrast to our first-generation, (super)stoichiometric protocol, this catalytic method enables faster and more efficient reactivity. Furthermore, lower oxidant concentration affords broader functional group tolerance, including alkenes, alkynes, alcohols, carbonyls, and heteroarenes. Mechanistic experiments interrogating the electronic nature of the key 1,5 H-atom transfer event are included, as well as probes for chemo-, regio-, and stereo-selectivity. 

The selective functionalization of remote C–H bonds via intramolecular hydrogen atom transfer (HAT) is transformative for organic synthesis. This radical-mediated strategy provides access to novel reactivity that is complementary to closed-shell pathways. As modern methods for mild generation of radicals are continually developed, inherent selectivity paradigms of HAT mechanisms offer unparalleled opportunities for developing new strategies for C–H functionalization. This review outlines the history, recent advances, and mechanistic underpinnings of intramolecular HAT as a guide to addressing ongoing challenges in this arena. 1 Introduction 2 Nitrogen-Centered Radicals 2.1 sp3 N-Radical Initiation 2.2 sp2 N-Radical Initiation 3 Oxygen-Centered Radicals 3.1 Carbonyl Diradical Initiation 3.2 Alkoxy Radical Initiation 3.3 Non-alkoxy Radical Initiation 4 Carbon-Centered Radicals 4.1 sp2 C-Radical Initiation 4.2 sp3 C-Radical Initiation 5 Conclusion 

The mechanism of the intermolecular hydroamination of 3‐methylbuta‐1,2‐diene (1) withN‐methylaniline (2) catalyzed by (IPr)AuOTf has been studied by employing a combination of kinetic analysis, deuterium labelling studies, and in situ spectral analysis of catalytically active mixtures. The results of these and additional experiments are consistent with a mechanism for hydroamination involving reversible, endergonic displacement ofN‐methylaniline from [(IPr)Au(NHMePh)]⁺(4) by allene to form the cationic gold π‐C1,C2‐allene complex [(IPr)Au(η²‐H₂C=C=CMe₂)]⁺(I), which is in rapid, endergonic equilibrium with the regioisomeric π‐C2,C3‐allene complex [(IPr)Au(η²‐Me₂C=C=CH₂)]⁺(I′). Rapid and reversible outer‐sphere addition of2to the terminal allene carbon atom ofI′to form gold vinyl complex (IPr)Au[C(=CH₂)CMe₂NMePh] (II) is superimposed on the slower addition of2to the terminal allene carbon atom ofIto form gold vinyl complex (IPr)Au[C(=CMe₂)CH₂NMePh] (III). Selective protodeauration ofIIIreleasesN‐methyl‐N‐(3‐methylbut‐2‐en‐1‐yl)aniline (3 a) with regeneration of4. At high conversion, gold vinyl complexIIis competitively trapped by an (IPr)Au⁺fragment to form the cationic bis(gold) vinyl complex {[(IPr)Au]₂[C(=CH₂)CMe₂NMePh]}⁺(6).