Palladium-Catalyzed Synthesis of 1H-1,2,3-Triazoles

Key words

1H-triazoles - palladium catalysis - XantPhos - sodium azide

Significance

A palladium-catalyzed synthesis of 1H-1,2,3-triazoles from sodium azide and alkenyl bromides with yields ranging from 45-93% is reported. Among the ligands tested, the large bite angle bidentate XantPhos shows the highest activity, which is attributed to its ability to behave as a trans-chelating ligand. The optimized conditions for alkyl-substituted alkenyl bromides are different from aryl-substituted ones in that increased catalyst loading, higher temperature and more polar solvents are required for the former systems. Electronic variations of the aryl ring do not significantly affect the results of the reaction and sensitive functional groups such as ester, nitrile and halogen are compatible with the reaction conditions. A mechanism involving a [3+2] cycloaddition of the azide anion with a vinylpalladium species has been proposed.

Comment

1,2,3-Triazoles represent a significant pharmaceutical and agrochemical class of heterocycles, e.g. due to their antitumor activity (L. S. Kallander et al. J. Med. Chem. 2005, 48, 5644-5647). Methods for construction of these heterocycles include the condensation of azides with phenacylidenetriphenylphosphorane (P. Ykman et al. Tetrahedron 1971, 27, 845-849), the reaction of dichloroacetaldehyde tosylhydrazone with amines (K. Harada et al. Tetrahedron 1998, 48, 695-698) and, especially, the widely used Huisgen reaction (‘click chemistry’), the copper-catalyzed reaction of terminal alkynes with azides (see review). However, these methodologies cannot directly lead to 1H-1,2,3-triazoles because inorganic azides are poor substrates for these reactions. This report provides a new access for 1H-1,2,3-trizaole ring construction.

Review

V. D. Bock et al. Eur. J. Org. Chem. 2006, 51-68.