biostudies-literaturePaioti PHSU.S. Department of Health & Human Services | NIH | Office of Extramural Research, National Institutes of HealthANRU.S. Department of Health & Human Services | NIH | Office of Extramural Research, National Institutes of Health (OER)Centre National de la Recherche ScientifiqueU.S. Department of Health & Human Services | National Institutes of Health (NIH)U.S. Department of Health & Human Services | National Institutes of HealthNIGMS NIH HHS426-436https://www.ebi.ac.uk/biostudies/studies/S-EPMC11326532biostudies-literatureUnknown16(3)The appeal of catalytic click chemistry is largely due to the copper-catalysed azide-alkyne cycloaddition (CuAAC) process, which is orthogonal to the more recently introduced sulfur-fluoride exchange (SuFEx). However, the triazole rings generated by CuAAC are not readily modifiable, and SuFEx connectors cannot be selectively functionalized, attributes that would be attractive in a click process. Here we introduce bisphosphine-copper-catalysed phenoxydiazaborinine formation (CuPDF), a link-and-in situ modify strategy for merging a nitrile, an allene, a diborane and a hydrazine. We also present copper- and palladium-catalysed quinoline formation (Cu/PdQNF), which is applicable in aqueous media, involving an aniline as the modifier. CuPDF and Cu/PdQNF are easy to perform and deliver robust, aNature chemistryClick processes orthogonal to CuAAC and SuFEx forge selectively modifiable fluorescent linkers.PMC11326532130395GM-130395R35 GM130395Del Pozo JLounsbury KEHackey MEFormica MRomiti FBauer VZandonella CHoveyda AHPaioti PHSfalseClick processes orthogonal to CuAAC and SuFEx forge selectively modifiable fluorescent linkers.The appeal of catalytic click chemistry is largely due to the copper-catalysed azide-alkyne cycloaddition (CuAAC) process, which is orthogonal to the more recently introduced sulfur-fluoride exchange (SuFEx). However, the triazole rings generated by CuAAC are not readily modifiable, and SuFEx connectors cannot be selectively functionalized, attributes that would be attractive in a click process. Here we introduce bisphosphine-copper-catalysed phenoxydiazaborinine formation (CuPDF), a link-and-in situ modify strategy for merging a nitrile, an allene, a diborane and a hydrazine. We also present copper- and palladium-catalysed quinoline formation (Cu/PdQNF), which is applicable in aqueous media, involving an aniline as the modifier. CuPDF and Cu/PdQNF are easy to perform and deliver robust, a2024-01-01T00:00:00Z2024 Mar2025-04-18T21:20:13.634Z2025-04-07T09:19:58.185ZS-EPMC113265323809309310.1038/s41557-023-01386-9