{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:20:14Z","timestamp":1760239214373,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2020,10,9]],"date-time":"2020-10-09T00:00:00Z","timestamp":1602201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["CTQ2016-77989-P"],"award-info":[{"award-number":["CTQ2016-77989-P"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Ullmann-type copper-mediated arylC-O bond formation has attracted the attention of the catalysis and organometallic communities, although the mechanism of these copper-catalyzed coupling reactions remains a subject of debate. We have designed well-defined triazamacrocyclic-based aryl-CuIII complexes as an ideal platform to study the C-heteroatom reductive elimination step with all kinds of nucleophiles, and in this work we focus our efforts on the straightforward synthesis of phenols by using H2O as nucleophile. Seven well-defined aryl-CuIII complexes featuring different ring size and different electronic properties have been reacted with water in basic conditions to produce final bis-phenoxo-CuII2 complexes, all of which are characterized by XRD. Mechanistic investigations indicate that the reaction takes place by an initial deprotonation of the NH group coordinated to CuIII center, subsequent reductive elimination with H2O as nucleophile to form phenoxo products, and finally air oxidation of the CuI produced to form the final bis-phenoxo-CuII2 complexes, whose enhanced stability acts as a thermodynamic sink and pushes the reaction forward. Furthermore, the corresponding triazamacrocyclic-CuI complexes react with O2 to undergo 1e\u2212 oxidation to CuII and subsequent C-H activation to form aryl-CuIII species, which follow the same fate towards bis-phenoxo-CuII2 complexes. This work further highlights the ability of the triazamacrocyclic-CuIII platform to undergo aryl-OH formation by reductive elimination with basic water, and also shows the facile formation of rare bis-phenoxo-CuII2 complexes.<\/jats:p>","DOI":"10.3390\/molecules25204595","type":"journal-article","created":{"date-parts":[[2020,10,17]],"date-time":"2020-10-17T07:23:22Z","timestamp":1602919402000},"page":"4595","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Bis-Phenoxo-CuII2 Complexes: Formal Aromatic Hydroxylation via Aryl-CuIII Intermediate Species"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2850-4409","authenticated-orcid":false,"given":"Xavi","family":"Ribas","sequence":"first","affiliation":[{"name":"Institut de Qu\u00edmica Computacional i Cat\u00e0lisi and Departament de Qu\u00edmica, Universitat de Girona, Campus Montilivi, E-17003 Girona, Catalonia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ra\u00fcl","family":"Xifra","sequence":"additional","affiliation":[{"name":"Institut de Qu\u00edmica Computacional i Cat\u00e0lisi and Departament de Qu\u00edmica, Universitat de Girona, Campus Montilivi, E-17003 Girona, Catalonia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9873-1332","authenticated-orcid":false,"given":"Xavier","family":"Fontrodona","sequence":"additional","affiliation":[{"name":"Serveis T\u00e8cnics de Recerca (STR), Universitat de Girona, Parc Cient\u00edfic i Tecnol\u00f2gic, E-17003 Girona, Catalonia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5400","DOI":"10.1002\/anie.200300594","article-title":"Modern synthetic methods for copper-mediated C(aryl)-O, C(aryl)-N, and C(aryl)-S bond formation","volume":"42","author":"Ley","year":"2003","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1002\/anie.200902245","article-title":"Copper(I) phenoxide complexes in the etherification of aryl halides","volume":"49","author":"Tye","year":"2010","journal-title":"Angew Chem. Int. Ed."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9971","DOI":"10.1021\/ja076668w","article-title":"Copper complexes of anionic nitrogen ligands in the amidation and imidation of aryl halides","volume":"130","author":"Tye","year":"2008","journal-title":"J. Am. Chem. Soc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3490","DOI":"10.1021\/ja068926f","article-title":"N-versus O-arylation of aminoalcohols: Orthogonal selectivity in copper-based catalysts","volume":"129","author":"Shafir","year":"2007","journal-title":"J. Am. Chem. Soc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"17423","DOI":"10.1021\/ja9081815","article-title":"Orthogonal Cu- and Pd-based catalyst systems for the O- and N-arylation of aminophenols","volume":"131","author":"Maiti","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6205","DOI":"10.1021\/ja100739h","article-title":"Computational explorations of mechanisms and ligand-directed selectivities of copper-catalyzed ullmann-type reactions","volume":"132","author":"Jones","year":"2010","journal-title":"J. Am. Chem. Soc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1039\/c3sc21818j","article-title":"The role of organometallic copper(III) complexes in homogeneous catalysis","volume":"4","author":"Casitas","year":"2013","journal-title":"Chem. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3054","DOI":"10.1021\/cr8002505","article-title":"Copper-mediated coupling reactions and their applications in natural products and designed biomolecules synthesis","volume":"108","author":"Evano","year":"2008","journal-title":"Chem. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Evano, G., and Blanchard, N. (2014). Modern Ullmann-Goldberg chemistry: Arylation of N-nucleophiles with aryl halides. Copper-Mediated Cross-Coupling Reactions, Wiley.","DOI":"10.1002\/9781118690659"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1515\/pac-2013-1104","article-title":"Cu(I)\/Cu(III) catalytic cycle involved in Ullmann-type cross-coupling reactions","volume":"86","author":"Ribas","year":"2014","journal-title":"Pure Appl. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1039\/c0sc00245c","article-title":"Direct Observation of CuI\/CuIII Redox Steps Relevant to Ullmann-Type Coupling Reactions","volume":"1","author":"Casitas","year":"2010","journal-title":"Chem. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Yao, B., Wang, D.-X., Huang, Z.-T., and Wang, M.-X. (2009). Room-temperature aerobic formation of a stable aryl-Cu(iii) complex and its reactions with nucleophiles: Highly efficient and diverse arene C-H functionalizations of azacalix[1]arene[3]pyridine. Chem. Commun., 2899\u20132901.","DOI":"10.1039\/b902946j"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3336","DOI":"10.1021\/jo300152u","article-title":"Cu(ClO4)2-mediated arene C-H bond halogenations of azacalixaromatics using alkali metal halides as halogen sources","volume":"77","author":"Yao","year":"2012","journal-title":"J. Org. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1021\/ol300205r","article-title":"Construction of Caryl\u2013Calkynyl Bond from Copper-Mediated Arene\u2013Alkyne and Aryl Iodide\u2013Alkyne Cross-Coupling Reactions: A Common Aryl-CuIII Intermediate in Arene C\u2013H Activation and Castro\u2013Stephens Reaction","volume":"14","author":"Wang","year":"2012","journal-title":"Org. Lett."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9418","DOI":"10.1039\/c2cc35067j","article-title":"Caryl-Calkyl bond formation from Cu(ClO4)2-mediated oxidative cross coupling reaction between arenes and alkyllithium reagents through structurally well-defined Ar-Cu(iii) intermediates","volume":"48","author":"Wang","year":"2012","journal-title":"Chem. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.1002\/1521-3773(20020816)41:16<2991::AID-ANIE2991>3.0.CO;2-6","article-title":"Aryl C-H Activation by Cu(II) To Form an Organometallic Aryl-Cu(III) Species: A Novel Twist on Copper Disproportionation","volume":"41","author":"Ribas","year":"2002","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"10005","DOI":"10.1002\/chem.201402711","article-title":"Aryl-copper(III)-acetylides as key intermediates in Csp2-Csp model couplings under mild conditions","volume":"20","author":"Rovira","year":"2014","journal-title":"Chem. Eur. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1002\/cctc.201200885","article-title":"Model Csp2-Csp3 Hurtley Coupling Catalysis that Operates through a Well-Defined CuI\/CuIII Mechanism","volume":"5","author":"Rovira","year":"2013","journal-title":"ChemCatChem"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"19386","DOI":"10.1021\/ja2058567","article-title":"Nucleophilic Aryl Fluorination and Aryl Halide Exchange Mediated by a Cu(I)\/Cu(III) Catalytic Cycle","volume":"133","author":"Casitas","year":"2011","journal-title":"J. Am. Chem. Soc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12068","DOI":"10.1021\/ja1045378","article-title":"Copper-Catalyzed Aerobic Oxidative Functionalization of an Arene C-H Bond: Evidence for an Aryl-Copper(III) Intermediate","volume":"132","author":"King","year":"2010","journal-title":"J. Am. Chem. Soc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"10458","DOI":"10.1039\/c0dt00284d","article-title":"Molecular mechanism of acid-triggered aryl-halide reductive elimination in well-defined aryl-CuIII-halide species","volume":"39","author":"Casitas","year":"2010","journal-title":"Dalton Trans."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.jorganchem.2017.02.004","article-title":"Direct use of CO2 for O-arylcarbamate synthesis via mild Cu(II)-catalyzed aerobic C-H functionalization in pincer-like macrocyclic systems","volume":"845","author":"Bernoud","year":"2017","journal-title":"J. Organomet. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5146","DOI":"10.1002\/chem.200500088","article-title":"Fine-Tuning the Electronic Properties of Highly Stable Organometallic CuIII Complexes Containing Monoanionic Macrocyclic Ligands","volume":"11","author":"Xifra","year":"2005","journal-title":"Chem. Eur. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"8786","DOI":"10.1039\/C7CC04491G","article-title":"A CuI\/CuIII prototypical organometallic mechanism for the deactivation of an active pincer-like CuI catalyst in Ullmann-type couplings","volume":"53","author":"Rovira","year":"2017","journal-title":"Chem. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7315","DOI":"10.1021\/acs.joc.6b01035","article-title":"Orthogonal Discrimination among Functional Groups in Ullmann-Type C\u2013O and C\u2013N Couplings","volume":"81","author":"Rovira","year":"2016","journal-title":"J. Org. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"10643","DOI":"10.1002\/chem.201100608","article-title":"Observation and Mechanistic Study of Facile C-O Bond Formation between a Well-Defined Aryl-Copper(III) Complex and Oxygen Nucleophiles","volume":"17","author":"Huffman","year":"2011","journal-title":"Chem. Eur. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6954","DOI":"10.1002\/anie.200804497","article-title":"Catalytic C-C, C-N anf C-O Ullmann-Type Coupling Reactions","volume":"48","author":"Monnier","year":"2009","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4105","DOI":"10.1021\/cr030011l","article-title":"The Baeyer\u2212Villiger Reaction:\u2009 New Developments toward Greener Procedures","volume":"104","author":"Arends","year":"2004","journal-title":"Chem. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1021\/cr00087a004","article-title":"Radical reactions of arenediazonium ions: An easy entry into the chemistry of the aryl radical","volume":"88","author":"Galli","year":"1988","journal-title":"Chem. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"10694","DOI":"10.1021\/ja0639719","article-title":"The Selective Reaction of Aryl Halides with KOH:\u2009 Synthesis of Phenols, Aromatic Ethers, and Benzofurans","volume":"128","author":"Anderson","year":"2006","journal-title":"J. Am. Chem. Soc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3688","DOI":"10.1021\/ol301523q","article-title":"Efficient Microwave-Assisted Pd-Catalyzed Hydroxylation of Aryl Chlorides in the Presence of Carbonate","volume":"14","author":"Yu","year":"2012","journal-title":"Org. Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1055\/s-0029-1219548","article-title":"An Efficient Synthesis of Phenol via CuI\/8-Hydroxyquinoline-Catalyzed Hydroxylation of Aryl Halides and Potassium Hydroxide","volume":"2010","author":"Maurer","year":"2010","journal-title":"Synlett"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.1021\/jo102506x","article-title":"CuI-Nanoparticles-Catalyzed Selective Synthesis of Phenols, Anilines, and Thiophenols from Aryl Halides in Aqueous Solution","volume":"76","author":"Xu","year":"2011","journal-title":"J. Org. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3033","DOI":"10.1021\/acs.orglett.7b01403","article-title":"Reagent Design and Ligand Evolution for the Development of a Mild Copper-Catalyzed Hydroxylation Reaction","volume":"19","author":"Fier","year":"2017","journal-title":"Org. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1055\/s-0037-1611894","article-title":"Room-Temperature Ionic Liquids (RTILs) as Green Media for Metal- and Base-Free ipso-Hydroxylation of Arylboronic Acids","volume":"30","author":"Shin","year":"2019","journal-title":"Synlett"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"14654","DOI":"10.1021\/ja907198n","article-title":"Pd(II)-Catalyzed Hydroxylation of Arenes with 1 atm of O2 or Air","volume":"131","author":"Zhang","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"12299","DOI":"10.1021\/ja101599e","article-title":"Facile C-H Bond Cleavage via a Proton-Coupled Electron Transfer Involving a C-H\u00b7\u00b7\u00b7CuII Interaction","volume":"132","author":"Ribas","year":"2010","journal-title":"J. Am. Chem. Soc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1039\/DT9840001349","article-title":"Synthesis, structure, and spectroscopic properties of copper(II) compounds containing nitrogen-sulfur donor ligands: The crystal and molecular structure of aqua[1,7-bis(N-methylbenzimidazol-2\u2032-yl)-2,6-dithiaheptane]copper(II) perchlorate","volume":"7","author":"Addison","year":"1984","journal-title":"J. Chem. Soc. Dalton Trans."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1002\/1099-0682(200203)2002:4<987::AID-EJIC987>3.0.CO;2-R","article-title":"A new Cu(I) complex that mimics the cresolase rection of tyrosinase. Crystal structure of its oxygenated Cu(II) complex","volume":"2002","author":"Fusi","year":"2002","journal-title":"Eur. J. Inorg. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"8796","DOI":"10.1039\/c1dt10428d","article-title":"Aryl-O reductive elimination from reaction of well-defined aryl-Cu(III) species with phenolates: The importance of ligand reactivity","volume":"40","author":"Casitas","year":"2011","journal-title":"Dalton Trans."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2941","DOI":"10.1002\/anie.200504222","article-title":"Regiospecific C-H Bond Activation: Reversible H\/D Exchange Promoted by CuI Complexes with Triazamacrocyclic Ligands","volume":"45","author":"Ribas","year":"2006","journal-title":"Angew. Chem. Int. Ed."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/20\/4595\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:17:50Z","timestamp":1760177870000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/20\/4595"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,9]]},"references-count":41,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["molecules25204595"],"URL":"https:\/\/doi.org\/10.3390\/molecules25204595","relation":{},"ISSN":["1420-3049"],"issn-type":[{"type":"electronic","value":"1420-3049"}],"subject":[],"published":{"date-parts":[[2020,10,9]]}}}