{"doi":"10.1021/jacs.5c14648","title":"Multisite Proton-Coupled Electron Transfer Enables Iodanyl Radical Catalysis","abstract":"High Resolution Image Download MS PowerPoint Slide The utility of hypervalent iodine reagents is often ascribed to the selective two-electron redox events that interconvert I(I), I(III), and I(V) species during substrate oxidation. We recently reported 1,2-diiodoveratrole ( 4a ) as an efficient catalyst for intramolecular oxidative C–H/N–H coupling and proposed that N–H activation was accomplished by an iodanyl radical (i.e., an I(I)/I(II) catalytic cycle) without accessing the corresponding I(III) derivative. Transient iodanyl radicals have been proposed during reductive activation of I(III) reagents, but the role of I(II) intermediates in substrate activation is underexplored. Here, we report a combined experimental and computational investigation of N–H activation and C–N coupling promoted by iodanyl radicals. The assembled data indicate that anodically generated iodanyl radicals directly promote C–H/N–H coupling through a multisite proton-coupled electron transfer (MS-PCET) mechanism where the iodanyl radical serves as an electron acceptor and a carboxylate additive serves as a proton acceptor. Based on these mechanistic insights, two second-generation catalysts─1-iodo-4-methoxy-2-(trifluoromethyl)benzene ( 4c ) and 6,7-diiodo-1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphthalene ( 4d )─were developed. These catalysts display tailored redox properties that significantly expand the scope of both intra- and intermolecular metal-free electrocatalytic C–N bond-forming chemistry. Together, these results demonstrate that (1) iodanyl radicals can engage directly in substrate activation without the intermediacy of I(III) species and (2) systematic variation of redox properties of iodanyl radicals enables rational catalyst optimization. The realization of one-electron hypervalent iodine mechanisms provides synthetic opportunities complementary to classical two-electron strategies and enables the development of new catalyst design concepts for metal-free electrocatalysis.","journal":"Journal of the American Chemical Society","year":2025,"id":527543,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9602,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":886907,"name":"Brandon L. Frey","orcid":"0000-0002-6041-1659","position":1,"is_corresponding":false},{"id":703976,"name":"Rémy F. Lalisse","orcid":"0000-0002-4556-5641","position":2,"is_corresponding":false},{"id":1404859,"name":"Lauv Patel","orcid":null,"position":3,"is_corresponding":false},{"id":1201261,"name":"Poulami Mukherjee","orcid":"0000-0002-2876-7612","position":4,"is_corresponding":false},{"id":408241,"name":"Zhihui Song","orcid":null,"position":5,"is_corresponding":false},{"id":684027,"name":"Raanan Carmieli","orcid":"0000-0003-4418-916X","position":6,"is_corresponding":false},{"id":348357,"name":"Osvaldo Gutiérrez","orcid":"0000-0001-8151-7519","position":7,"is_corresponding":false},{"id":298861,"name":"David C. Powers","orcid":"0000-0003-3717-2001","position":8,"is_corresponding":false},{"id":1082451,"name":"Phong Thai","orcid":"0000-0001-6283-9344","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T02:50:39.280101Z","pmid":"41252562","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":[]}