[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-450019-105":3,"detail-sidebar-cat-0-en-105":80,"doc-detail-450019-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":73,"head_meta":75,"extra_data":77,"updated_unix":79},105,"en","photochemical-cuiii-mediated-trifluoromethylation-of-heteroarenes-and-biomolecules-edge-article","Photochemical Cu(III)-mediated trifluoromethylation of (hetero)arenes and biomolecules - EDGE ARTICLE","","A highly efficient, atom-economical C–H trifluoromethylation method for (hetero)arenes and complex biomolecules is developed using a substoichiometric amount of the stable tetrakis(trifluoromethyl)cuprate(III) salt. Under violet-light irradiation with an oxidant, four CF3 groups sequentially generate trifluoromethyl radicals, enabling high-yield transformations under mild conditions. The approach shows strong functional group tolerance and supports late-stage labeling of pharmaceuticals and biomolecules. Mechanistic studies support a photoinitiated radical pathway and full utilization of Cu(III) species.",{"@graph":14,"@context":72},[15,34,55],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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reagent and light source enable the Cu(III)-mediated trifluoromethylation?","Question",{"text":62,"@type":63},"The method uses substoichiometric tetrakis(trifluoromethyl)cuprate(III) and violet-light irradiation (LED) in the presence of an oxidant to generate trifluoromethyl radicals.","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"What advantage does the protocol provide for incorporating CF3 groups?",{"text":67,"@type":63},"It sequentially converts all four CF3 groups into reactive radicals, allowing high-yielding transformations under mild conditions and improving atom economy compared with systems that underutilize CF3 ligands.",{"name":69,"@type":60,"acceptedAnswer":70},"Which types of substrates are reported to be compatible?",{"text":71,"@type":63},"The protocol is applicable to (hetero)arenes and complex biomolecules, including late-stage trifluoromethylation of pharmaceuticals, amino acids, and nucleosides.","https://schema.org",{"og:url":32,"og:type":74,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":76,"canonical":32},"index,follow",{"doc_id":78,"site_id":7},450019,1790795187,{"code":4,"msg":81,"data":82},"success",[83,87,91,95,100,105,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":84,"show_sort_weight":85,"slug":86},"Story & 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.1039/d5sc07405c  \nAll publication charges for this article have been paid for by the Royal Society of Chemistry  \nReceived 24th September 2025  \nAccepted 6th November 2025 DOI: 10.1039/d5sc07405c[rsc.li/chemical-science](rsc.li/chemical-science)  \nPhotochemical Cu( III)-mediated trifluoromethylation of (hetero)arenes and biomolecules  \nPetr Posp il, ab Vladimir Motornov,  *ad Ondrej Michal,ˇac Lucie ˇSlkov,  ac So a Bohov,a Tom Slanina,  a Jn Tarbek,  a Blanka Klepeta and Petr Beier  *a  \nA highly efficient and atom-economical method for the C–H trifluoromethylation of (hetero)arenes and complex biomolecules has been developed using a substoichiometric amount of the stable tetrakis(trifluoromethyl)cuprate(III) salt. Upon violet-light irradiation in the presence of an oxidant, all four CF3 groups are sequentially converted into trifluoromethyl radicals, enabling high-yielding transformations under mild conditions. The protocol exhibits excellent functional group tolerance and is applicable to the late-stage trifluoromethylation of pharmaceuticals, amino acids, and nucleosides. Mechanistic studies support a photoinitiated radical pathway and reveal the full utilization of the Cu(III) species. The results presented advance the use of copper-mediated strategies for the sustainable incorporation of fluorine into complex molecules.  \nIntroduction  \nCu(III) tri􀀁uoromethyl compounds have received wide interest from organic and inorganic chemists due to their exceptional stability and versatile reactivity (Scheme 1A) .1 Since the breakthrough discovery by Grushin in 2015, who described a simple procedure for the preparation of tetrakis(tri􀀁uoromethyl) cuprate salts [Cu(CF3)4] − from CuCl with air as the only oxidant,2 Cu(III) tri􀀁uoromethyl complexes have become candidates for applications in organic synthesis, especially as tri-􀀁uoromethylation agents.1a However, homoleptic tetrakis(tri􀀁uoromethyl)-cuprate(III) salts are known to be poor tri􀀁uoromethylation agents. They have been shown to be activated to release tri􀀁uoromethyl radicals by harsh UV irradiation with only low efficiency (Scheme 1B),3 or by electrospray ionization.4 Therefore, neutral complexes with bidentate N-donor ligands, such as (bpy)Cu(CF3)3 (ref. 5) and (phen)Cu(CF3)3,6 are the most explored copper(III) tri􀀁uoromethyl transfer reagents, even though they exhibit limited atom economy in tri􀀁uoromethylation.  \naInstitute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo nam. 2, 16600, Prague, Czech Republic. E-mail: [beier@uochb.cas.cz](beier@uochb.cas.cz); [cuprate51@gmail.com](cuprate51@gmail.com)  \nbInstitute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentsk 573, 53210, Pardubice, Czech Republic cDepartment of Physical Chemistry, University of Chemistry and Technology, Prague, Technick 5, 16628, Prague, Czech Republic  \ndFreie Universitt Berlin, Fabeckstraße 34-36, 14195 Berlin, Germany  \nWe have recently described oxygen-donor solvate complexes (DMF)2Cu(CF3)3,7 and bis(tri􀀁uoromethyl)-1,3-diketonates8 bearing two tri􀀁uoromethyl groups which showed high  \nScheme 1 Reactivity of Cu(III) complexes in aromatic C–H trifluoromethylation.  \n© 2025 The Author(s) . Published by the Royal Society of Chemistry Chem. Sci.  \nChemical Science Edge Article  \nreactivities in tri􀀁uoromethylation reactions. Moreover, a highly reactive Cu(III) complex with only one tri􀀁uoromethyl group stabilized by a pyridine-2,6-dicarboxamide ligand has recently been reported.9 All these complexes are used as versatile stoichiometric C–H tri􀀁uoromethylation reagents under mild conditions (Scheme 1C), the reactivity of which increases with the decreasing number of CF3 ligands. However, no reported transformation starting from Cu(III) tri􀀁uoromethyl complexes to date achieved the complete utilization of all tri-􀀁uoromethyl groups in reactions, highlighting the need for an","cbCaihex2SiQgbG8","https://ap.wps.com/l/cbCaihex2SiQgbG8","pdf",1462757,"English","# Introduction\n# Results and discussion\n## Optimization of substoichiometric trifluoromethylation","[{\"question\":\"What reagent and light source enable the Cu(III)-mediated trifluoromethylation?\",\"answer\":\"The method uses substoichiometric tetrakis(trifluoromethyl)cuprate(III) and violet-light irradiation (LED) in the presence of an oxidant to generate trifluoromethyl radicals.\"},{\"question\":\"What advantage does the protocol provide for incorporating CF3 groups?\",\"answer\":\"It sequentially converts all four CF3 groups into reactive radicals, allowing high-yielding transformations under mild conditions and improving atom economy compared with systems that underutilize CF3 ligands.\"},{\"question\":\"Which types of substrates are reported to be compatible?\",\"answer\":\"The protocol is applicable to (hetero)arenes and complex biomolecules, including late-stage trifluoromethylation of pharmaceuticals, amino acids, and nucleosides.\"}]","Photochemical Cu(III)-mediated trifluoromethylation of (hetero)arenes and biomolecules - EDGE ARTICLE | PDF",1790731839,15]