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

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

Povzetek

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.

Ključne besede

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

Podatki

Jezik:	Angleški jezik
Leto izida:	2022
Tipologija:	1.01 - Izvirni znanstveni članek
Organizacija:	UL FKKT - Fakulteta za kemijo in kemijsko tehnologijo
UDK:	547.79:544.473-039.63
COBISS:	97425923
ISSN:	0022-3263
Št. ogledov:	163
Št. prenosov:	45
Ocena:	0 (0 glasov)
Metapodatki:

Ostali podatki

Sekundarni jezik:	Slovenski jezik
Sekundarne ključne besede:	CuAAC;alkini;azidi;baker;kataliza;
Vrsta dela (COBISS):	Članek v reviji
Strani:	str. 4018-4028
Letnik:	ǂVol. ǂ87
Zvezek:	ǂiss. ǂ6
Čas izdaje:	18 Mar. 2022
DOI:	10.1021/acs.joc.1c02775
ID:	15427845