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

Abstract

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.

Keywords

CuAAC;alkini;azidi;baker;kataliza;alkynes;azides;copper;catalysis;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL FKKT - Faculty of Chemistry and Chemical Technology
UDC: 547.79:544.473-039.63
COBISS: 97425923 Link will open in a new window
ISSN: 0022-3263
Views: 163
Downloads: 45
Average score: 0 (0 votes)
Metadata: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Other data

Secondary language: Slovenian
Secondary keywords: CuAAC;alkini;azidi;baker;kataliza;
Type (COBISS): Article
Pages: str. 4018-4028
Volume: ǂVol. ǂ87
Issue: ǂiss. ǂ6
Chronology: 18 Mar. 2022
DOI: 10.1021/acs.joc.1c02775
ID: 15427845