{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T16:11:14Z","timestamp":1788970274171,"version":"build-2803163510"},"reference-count":48,"publisher":"American Chemical Society (ACS)","issue":"35","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001459","name":"Ministry of Education - Singapore","doi-asserted-by":"publisher","award":["MOE-T2EP10223-0003"],"award-info":[{"award-number":["MOE-T2EP10223-0003"]}],"id":[{"id":"10.13039\/501100001459","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001381","name":"National Research Foundation Singapore","doi-asserted-by":"publisher","award":["NRF-CRP27-2021-0001"],"award-info":[{"award-number":["NRF-CRP27-2021-0001"]}],"id":[{"id":"10.13039\/501100001381","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001475","name":"Nanyang Technological University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001475","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Nitrogen-containing heteroarenes, particularly diazines (six-membered dinitrogen aromatics) and diazoles (five-membered dinitrogen aromatics), constitute the bedrock of modern pharmaceutical and agrochemical architectures. Synthetic capability to edit these heteroaromatic scaffolds through precise core-atom transformations opens the door to previously untapped chemical spaces, thus accelerating discovery campaigns for developing pharmaceutical drugs and agrochemicals. Here we report a photocatalytic platform for the skeletal remodeling of diazines into diazoles, encompassing three distinct permutations: conversion of pyrimidines (1,3-diazines) to imidazoles (1,3-diazoles), and pyridazines (1,2-diazines) to pyrazoles (1,2-diazoles) facilitated by formal ring contractions that proceed via either rehybridizative transposition or deletion of an aromatic carbon unit. Key to this strategy is harnessing photocatalytic single-electron transfer (SET) to access dearomatized diazacyclohexadienyl anions, which undergo precisely orchestrated ring contraction via disrotatory 6\u03c0-1,5-electrocyclization.<\/jats:p>","DOI":"10.1021\/jacs.6c14314","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T15:44:19Z","timestamp":1788191059000},"page":"38491-38499","source":"Crossref","is-referenced-by-count":0,"title":["Diazines-to-Diazoles\nSkeletal Remodeling"],"prefix":"10.1021","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0391-2746","authenticated-orcid":true,"given":"Tian-Yu","family":"Peng","sequence":"first","affiliation":[{"name":"Nanyang Technological University , , ,","place":["Singapore, Singapore, 637371"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene Yew Kun","family":"Tan","sequence":"additional","affiliation":[{"name":"Nanyang Technological University , , ,","place":["Singapore, Singapore, 637371"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taku","family":"Wakabayashi","sequence":"additional","affiliation":[{"name":"Nanyang Technological University , , ,","place":["Singapore, Singapore, 637371"]},{"name":"Cambridge Centre for Advanced Research and Education in Singapore (CARES) , ,","place":["Singapore, Singapore, 138602"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0775-0334","authenticated-orcid":true,"given":"Yaoyue","family":"Liu","sequence":"additional","affiliation":[{"name":"Nanyang Technological University , , ,","place":["Singapore, Singapore, 637371"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2039-023X","authenticated-orcid":true,"given":"Shunsuke","family":"Chiba","sequence":"additional","affiliation":[{"name":"Nanyang Technological University , , ,","place":["Singapore, Singapore, 637371"]},{"name":"Cambridge Centre for Advanced Research and Education in Singapore (CARES) , ,","place":["Singapore, Singapore, 138602"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"2026090910095694300_cit1","doi-asserted-by":"publisher","first-page":"11622","DOI":"10.1021\/acs.jmedchem.4c01122","article-title":"An Update\non the Nitrogen Heterocycle Compositions and Properties of U.S. FDA-Approved\nPharmaceuticals (2013\u20132023)","volume":"67","author":"Marshall","year":"2024","journal-title":"J. Med.\nChem."},{"key":"2026090910095694300_cit2","doi-asserted-by":"publisher","first-page":"8699","DOI":"10.1021\/acs.jmedchem.2c00473","article-title":"Rings in\nClinical Trials and Drugs: Present and Future","volume":"65","author":"Shearer","year":"2022","journal-title":"J. Med. Chem."},{"key":"2026090910095694300_cit3","doi-asserted-by":"publisher","first-page":"3552","DOI":"10.1021\/acs.jmedchem.6b01807","article-title":"The Necessary\nNitrogen Atom: A Versatile High-Impact\nDesign Element for Multiparameter Optimization","volume":"60","author":"Pennington","year":"2017","journal-title":"J. Med. Chem."},{"key":"2026090910095694300_cit4","doi-asserted-by":"publisher","first-page":"1853","DOI":"10.1007\/s00044-023-03035-9","article-title":"The pyridazine\nheterocycle in molecular recognition and drug discovery","volume":"32","author":"Meanwell","year":"2023","journal-title":"Med. Chem. Res."},{"key":"2026090910095694300_cit5","doi-asserted-by":"publisher","first-page":"110902","DOI":"10.1016\/j.cclet.2025.110902","article-title":"Pyridazine: A privileged\nscaffold in the development of 21st-century\npesticides","volume":"36","author":"Chen","year":"2025","journal-title":"Chin. Chem. Lett."},{"key":"2026090910095694300_cit6","doi-asserted-by":"publisher","first-page":"1786","DOI":"10.1021\/acs.accounts.5c00174","article-title":"Skeletal Editing Strategies\nDriven by Total Synthesis","volume":"58","author":"Kim","year":"2025","journal-title":"Acc. Chem. Res."},{"key":"2026090910095694300_cit7","doi-asserted-by":"publisher","first-page":"11459","DOI":"10.1021\/acs.jmedchem.4c01347","article-title":"Rational Molecular\nEditing: A New Paradigm in Drug Discovery","volume":"67","author":"Ma","year":"2024","journal-title":"J.\nMed. Chem."},{"key":"2026090910095694300_cit8","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/d41586-023-01735-1","article-title":"Almost magical:\nchemists can now move single atoms in and out of a molecule\u2019s\ncore","volume":"618","author":"Peplow","year":"2023","journal-title":"Nature"},{"key":"2026090910095694300_cit9","doi-asserted-by":"publisher","first-page":"114483","DOI":"10.1016\/j.ejmech.2022.114483","article-title":"Ring replacement\nrecommender:\nRing modifications for improving biological activity","volume":"238","author":"Ertl","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"2026090910095694300_cit10","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1038\/s44160-022-00052-1","article-title":"Single-atom\nlogic for heterocycle editing","volume":"1","author":"Jurczyk","year":"2022","journal-title":"Nat. Synth."},{"key":"2026090910095694300_cit11","doi-asserted-by":"publisher","first-page":"5810","DOI":"10.1039\/C9CS00478E","article-title":"Carbodiimide-based\nsynthesis of N-heterocycles:\nmoving from two classical reactive sites to chemical bond breaking\/forming\nreaction","volume":"49","author":"Wang","year":"2020","journal-title":"Chem. Soc. Rev."},{"key":"2026090910095694300_cit12","doi-asserted-by":"publisher","first-page":"2942","DOI":"10.1021\/cr300122t","article-title":"Acid Hydrazides,\nPotent Reagents for Synthesis of Oxygen-, Nitrogen-, and\/or Sulfur-Containing\nHeterocyclic Rings","volume":"114","author":"Majumdar","year":"2014","journal-title":"Chem. Rev."},{"key":"2026090910095694300_cit13","doi-asserted-by":"publisher","first-page":"6984","DOI":"10.1021\/cr2000459","article-title":"From 2000\nto Mid-2010: A Fruitful Decade for the Synthesis of Pyrazoles","volume":"111","author":"Fustero","year":"2011","journal-title":"Chem. Rev."},{"key":"2026090910095694300_cit14","doi-asserted-by":"publisher","first-page":"2958","DOI":"10.1021\/cr300176g","article-title":"Arylglyoxals\nin Synthesis of Heterocyclic\nCompounds","volume":"113","author":"Eftekhari-Sis","year":"2013","journal-title":"Chem. Rev."},{"key":"2026090910095694300_cit15","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1055\/sos-SD-012-00002","article-title":"Product Class 1: Pyrazoles","volume-title":"Science of Synthesis","author":"Stanovnik","year":"2002"},{"key":"2026090910095694300_cit16","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1055\/sos-SD-012-00398","article-title":"Product Class\n3: Imidazoles","volume-title":"Science of Synthesis","author":"Grimmett","year":"2002"},{"key":"2026090910095694300_cit17","doi-asserted-by":"publisher","first-page":"6027","DOI":"10.1021\/acs.jmedchem.4c02839","article-title":"Chem Analysis of Core-Atom Transformations in Pharmaceutically\nRelevant Heteroaromatics","volume":"68","author":"Bartholomew","year":"2025","journal-title":"J. Med. Chem."},{"key":"2026090910095694300_cit18","doi-asserted-by":"publisher","first-page":"4915","DOI":"10.1016\/S0040-4020(01)93143-6","article-title":"Hetarylnitrenes\nI: Ring contraction and fragmentation\nin nitrenodiazines","volume":"26","author":"Wentrup","year":"1970","journal-title":"Tetrahedron"},{"key":"2026090910095694300_cit19","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1002\/recl.19690880614","article-title":"Ring transformations\nin reactions of heterocyclic compounds with nucleophiles. Part. XVI:\nA tracer study of the formation of 4(5)-ethynyl-2-phenylimidazole\nfrom 4-chloro-5-methyl-2-phenylpyrimidine by potassium amide in liquid\nammonia","volume":"88","author":"van Meeteren","year":"1969","journal-title":"Recl. Trav. Chim. Pays-Bas"},{"key":"2026090910095694300_cit20","doi-asserted-by":"publisher","first-page":"1727","DOI":"10.1002\/jhet.5570210631","article-title":"Pyridazines. XXIII. A novel pyridazine\ninto pyrazole\nring transformation","volume":"21","author":"Heinisch","year":"1984","journal-title":"J. Heterocycl. Chem."},{"key":"2026090910095694300_cit21","doi-asserted-by":"publisher","first-page":"22309","DOI":"10.1021\/jacs.2c10746","article-title":"Skeletal Editing of\nPyrimidines to\nPyrazoles by Formal Carbon Deletion","volume":"144","author":"Bartholomew","year":"2022","journal-title":"J. Am.\nChem. Soc."},{"key":"2026090910095694300_cit22","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/s41586-024-07474-1","article-title":"A deconstruction-reconstruction\nstrategy\nfor pyrimidine diversification","volume":"631","author":"Uhlenbruck","year":"2024","journal-title":"Nature"},{"key":"2026090910095694300_cit23","doi-asserted-by":"publisher","first-page":"12860","DOI":"10.1039\/D6SC03470E","article-title":"A photochemical strategy for pyrazole\nto imidazole conversion","volume":"17","author":"Wei","year":"2026","journal-title":"Chem. Sci."},{"key":"2026090910095694300_cit24","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1002\/cjoc.202200583","article-title":"Overview of 6\u03c0 1,5-Electrocyclization over the\nPast 40 Years","volume":"41","author":"Huang","year":"2023","journal-title":"Chin. J. Chem."},{"key":"2026090910095694300_cit25","doi-asserted-by":"publisher","first-page":"6202","DOI":"10.1021\/ja01050a060","article-title":"Orbital symmetry in a carbanion cyclization","volume":"91","author":"Hunter","year":"1969","journal-title":"J. Am. Chem. Soc."},{"key":"2026090910095694300_cit26","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1038\/s44160-026-01023-6","article-title":"Peripheral aryl group\ntransposition on pyridines using photoredox catalysis","volume":"5","author":"Tan","year":"2026","journal-title":"Nat. Synth."},{"key":"2026090910095694300_cit27","doi-asserted-by":"publisher","first-page":"3722","DOI":"10.1016\/j.chempr.2024.09.016","article-title":"Dearomative\ndimerization of quinolines and their skeletal rearrangement to indoles\ntriggered by single-electron transfer","volume":"10","author":"Tan","year":"2024","journal-title":"Chem"},{"key":"2026090910095694300_cit28","doi-asserted-by":"publisher","first-page":"2145","DOI":"10.1039\/C9CS00311H","article-title":"Visible-light induced\ndearomatization reactions","volume":"51","author":"Cheng","year":"2022","journal-title":"Chem. Soc. Rev."},{"key":"2026090910095694300_cit29","doi-asserted-by":"publisher","first-page":"15353","DOI":"10.1021\/jacs.8b08933","article-title":"A Toolbox Approach To Construct Broadly\nApplicable Metal-Free Catalysts for Photoredox Chemistry: Deliberate\nTuning of Redox Potentials and Importance of Halogens in Donor\u2013Acceptor\nCyanoarenes","volume":"140","author":"Speckmeier","year":"2018","journal-title":"J. Am. Chem. Soc."},{"key":"2026090910095694300_cit30","doi-asserted-by":"publisher","first-page":"2351","DOI":"10.1016\/S0040-4020(01)90617-9","article-title":"High-yielding syntheses of 4(5)-substituted\nimidazoles\nvia organolithium intermediates. the utility of sulphonamide n-protection\nand silicon-containing blocking groups","volume":"42","author":"Carpenter","year":"1986","journal-title":"Tetrahedron"},{"key":"2026090910095694300_cit31","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/nrd839","article-title":"Glivec (STI571, imatinib),\na rationally developed, targeted anticancer drug","volume":"1","author":"Capdeville","year":"2002","journal-title":"Nat. Rev. Drug Discovery"},{"key":"2026090910095694300_cit32","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s13065-020-00730-1","article-title":"Synthesis and therapeutic\npotential of imidazole containing\ncompounds","volume":"15","author":"Siwach","year":"2021","journal-title":"BMC Chem."},{"key":"2026090910095694300_cit33","doi-asserted-by":"publisher","first-page":"12071","DOI":"10.1021\/acs.joc.9b02003","article-title":"Redox Property of Enamines","volume":"84","author":"Li","year":"2019","journal-title":"J. Org. Chem."},{"key":"2026090910095694300_cit34","doi-asserted-by":"publisher","first-page":"2695","DOI":"10.1021\/acs.chemrev.1c00388","article-title":"Aryl\nTransfer Strategies Mediated\nby Photoinduced Electron Transfer","volume":"122","author":"Allen","year":"2022","journal-title":"Chem. Rev."},{"key":"2026090910095694300_cit35","doi-asserted-by":"publisher","first-page":"5220","DOI":"10.1039\/C4CS00467A","article-title":"Radical\naryl migration reactions\nand synthetic applications","volume":"44","author":"Chen","year":"2015","journal-title":"Chem. Soc. Rev."},{"key":"2026090910095694300_cit36","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1055\/s-0035-1561297","article-title":"Experimental and Calculated Electrochemical\nPotentials of Common Organic Molecules for Applications to Single-Electron\nRedox Chemistry","volume":"27","author":"Roth","year":"2016","journal-title":"Synlett"},{"key":"2026090910095694300_cit37","doi-asserted-by":"publisher","first-page":"4863","DOI":"10.1016\/S0040-4039(00)85733-0","article-title":"Isomerizationi of small ring lithium\ndialkylamides","volume":"23","author":"Newcomb","year":"1982","journal-title":"Tetrahedron Lett."},{"key":"2026090910095694300_cit38","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1055\/s-2005-869850","article-title":"Synthesis of N-Protected\n\u03b2-Aminocyclopropanedicarboxylates\nand Their Ring Transformation to N-Benzhydryl-3-alkoxycarbonyl-4,4-dialkyl-pyrrolidin-2-ones","volume":"2005","author":"Mangelinckx","year":"2005","journal-title":"Synlett"},{"key":"2026090910095694300_cit39","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1002\/recl.19831020706","article-title":"Photochemical ring\ncontraction of 4-heteroaryl-substituted 1,4(or 3,4)-dihydropyrimidines\ninto imidazoles","volume":"102","author":"van der Stoel","year":"1983","journal-title":"Recl. Trav. Chim. Pays-Bas"},{"key":"2026090910095694300_cit40","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/s44160-025-00986-2","article-title":"Chemical reactivity from the perspective\nof enthalpic\ncoupling","volume":"5","author":"Brien","year":"2026","journal-title":"Nat. Synth."},{"key":"2026090910095694300_cit41","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1128\/jb.02352-14","article-title":"Small-Molecule Inhibitors of Gram-Negative\nLipoprotein\nTrafficking Discovered by Phenotypic Screening","volume":"197","author":"McLeod","year":"2015","journal-title":"J. Bacteriol."},{"key":"2026090910095694300_cit42","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.2174\/1568026619666190808145235","article-title":"Homologation:\nA Versatile Molecular\nModification Strategy to Drug Discovery","volume":"19","author":"Lima","year":"2019","journal-title":"Curr.\nTop. Med. Chem."},{"key":"2026090910095694300_cit43","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1038\/s41586-025-09159-9","article-title":"One-carbon homologation\nof alkenes","volume":"643","author":"Grocott","year":"2025","journal-title":"Nature"},{"key":"2026090910095694300_cit44","doi-asserted-by":"publisher","first-page":"1775","DOI":"10.1039\/C9MD00228F","article-title":"Discovery of new\nnon-acidic lonazolac\nanalogues with COX-2 selectivity as potent anti-inflammatory agents","volume":"10","author":"Harras","year":"2019","journal-title":"Med. Chem. Comm."},{"key":"2026090910095694300_cit45","doi-asserted-by":"publisher","first-page":"26124","DOI":"10.1021\/jacs.5c09085","article-title":"Radical 1,3-Difunctionalization\nof \u03b2,\u03b3-Unsaturated Ketones\nvia Concomitant 1,2-Carbonyl Migration: An Entrance to \u03b2-SF5-\/\u03b2-CF3SF4 Ketones","volume":"147","author":"Li","year":"2025","journal-title":"J. Am. Chem. Soc."},{"key":"2026090910095694300_cit46","doi-asserted-by":"publisher","first-page":"5578","DOI":"10.1021\/jo049658b","article-title":"Copper\u2013Diamine-Catalyzed\nN-Arylation of Pyrroles, Pyrazoles, Indazoles, Imidazoles, and Triazoles","volume":"69","author":"Antilla","year":"2004","journal-title":"J. Org. Chem."},{"key":"2026090910095694300_cit47","doi-asserted-by":"publisher","first-page":"3349","DOI":"10.1016\/j.bmcl.2013.03.093","article-title":"2-(1H-Pyrazol-4-yl)acetic\nacids as CRTh2 antagonists","volume":"23","author":"Andre\u0301s","year":"2013","journal-title":"Bioorg. Med. Chem.\nLett."},{"key":"2026090910095694300_cit48","doi-asserted-by":"publisher","first-page":"3468","DOI":"10.1039\/D1GC00487E","article-title":"Ring-contraction\nof hantzsch esters and their derivatives\nto pyrroles via electrochemical extrusion of ethyl acetate out of\naromatic rings","volume":"23","author":"Liu","year":"2021","journal-title":"Green Chem."}],"container-title":["Journal of the American\nChemical Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/jacs.6c14314","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jacsat\/article-pdf\/148\/35\/38491\/67371395\/jacs.6c14314.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jacsat\/article-pdf\/148\/35\/38491\/67371395\/jacs.6c14314.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T15:28:06Z","timestamp":1788967686000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jacsat\/article\/148\/35\/38491\/5326164\/Diazines-to-Diazoles-Skeletal-Remodeling"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,24]]},"references-count":48,"journal-issue":{"issue":"35","published-online":{"date-parts":[[2026,8,24]]},"published-print":{"date-parts":[[2026,9,9]]}},"URL":"https:\/\/doi.org\/10.1021\/jacs.6c14314","relation":{},"ISSN":["0002-7863","1520-5126"],"issn-type":[{"value":"0002-7863","type":"print"},{"value":"1520-5126","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,24]]}}}