1H-triazoles - palladium catalysis - XantPhos - sodium azide
Significance
<P>A palladium-catalyzed synthesis of 1
H-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.</P>
Comment
<P>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 1
H-1,2,3-triazoles because inorganic azides are poor substrates for these reactions.
This report provides a new access for 1
H-1,2,3-trizaole ring construction.</P>
