{"doi":"10.1021/jacs.1c07330","title":"Mechanistic Investigation of the Iron-Catalyzed Azidation of Alkyl C(<i>sp</i><sup>3</sup>)–H Bonds with Zhdankin’s λ<sup>3</sup>-Azidoiodane","abstract":"An in-depth study of the mechanism of the azidation of C(sp3)–H bonds with Zhdankin’s λ3-azidoiodane reagent catalyzed by iron(II)(pybox) complexes is reported. Previously, it was shown that tertiary and benzylic C(sp3)–H bonds of a range of complex molecules underwent highly site-selective azidation by reaction with a λ3-azidoiodane reagent and an iron(II)(pybox) catalyst under mild conditions. However, the mechanism of this reaction was unclear. Here, a series of mechanistic experiments are presented that reveal critical features responsible for the high selectivity and broad scope of this reaction. These experiments demonstrate the ability of the λ3-azidoiodane reagent to undergo I–N bond homolysis under mild conditions to form λ2-iodanyl and azidyl radicals that undergo highly site-selective and rate-limiting abstraction of a hydrogen atom from the substrate. The resultant alkyl radical then combines rapidly with a resting state iron(III)-azide complex, which is generated by the reaction of the λ3-azidoiodane with the iron(II)(pybox) complex, to form the C(sp3)–N3 bond. This mechanism is supported by the independent synthesis of well-defined iron complexes characterized by cyclic voltammetry, X-ray diffraction, and EPR spectroscopy, and by the reaction of the iron complexes with alkanes and the λ3-azidoiodane. Reaction monitoring and kinetic studies further reveal an unusual effect of the catalyst on the rate of formation of product and consumption of reactants and suggest a blueprint for the development of new processes leading to late-stage functionalization of C(sp3)–H bonds.","journal":"Journal of the American Chemical Society","year":2021,"id":162079,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":51,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.947,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":660129,"name":"Alexander Fawcett","orcid":"0000-0003-1880-3269","position":1,"is_corresponding":false},{"id":240863,"name":"Ruchira Chatterjee","orcid":"0000-0002-0865-061X","position":2,"is_corresponding":false},{"id":242491,"name":"John F. Hartwig","orcid":"0000-0002-4157-468X","position":3,"is_corresponding":false},{"id":678301,"name":"Craig S. Day","orcid":"0000-0002-6931-0280","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-18T23:45:00.600065Z","pmid":"34559970","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}