Copper-catalyzed azide–alkyne cycloaddition of hydrazoic acid formed in situ from sodium azide affords 4-monosubstituted-1,2,3-triazoles

Jankovič, Dominik (author), Virant, Miha (author), Gazvoda, Martin (author)

We report a copper-catalyzed cycloaddition of hydrogen azide (hydrazoic acid, HN$_3$) with terminal alkynes to form 4-substituted-1H-1,2,3-triazoles in a sustainable manner. Hydrazoic acid was formed in situ from sodium azide under acidic conditions to react with terminal alkynes in a copper-catalyzed reaction. Using polydentate N-donor chelating ligands and mild organic acids, the reactions were realized to proceed at room temperature under aerobic conditions in a methanol–water mixture and with 5 mol % catalyst loadings to afford 4-substituted-1,2,3-triazoles in high yields. This method is amenable on a wide range of alkyne substrates, including unprotected peptides, showing diverse functional group tolerance. It is applicable for late-stage functionalization synthetic strategies, as demonstrated in the synthesis of the triazole analogue of losartan. The preparation of orthogonally protected azahistidine from Fmoc-L-propargylglycine was realized on a gram scale. The hazardous nature of hydrazoic acid has been diminished as it forms in situ in <6% concentrations at which it is safe to handle. Reactions of distilled solutions of hydrazoic acid indicated its role as a reactive species in the copper-catalyzed reaction.

• Language: English
• Keywords: CuAAC, alkynes, azides, copper, catalysis
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Version of Record
• Year: 2022
• Number of pages: Str. 4018–4028
• Numbering: Vol. 87, iss. 6
• PID: 20.500.12556/RUL-136959
• UDC: 547.79:544.473-039.63
• ISSN on article: 0022-3263
• DOI: 10.1021/acs.joc.1c02775
• COBISS.SI-ID: 97425923
• Publication date in RUL: 26.05.2022

Record is a part of a journal

• Title: Journal of organic chemistry
• Shortened title: J. org. chem.
• Publisher: American Chemical Society
• ISSN: 0022-3263
• COBISS.SI-ID: 235287

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: CuAAC, alkini, azidi, baker, kataliza