Synthesis of Fused Triazoles via Azide-[3+2] Cycloaddition and Ring-Closing Metathesis

Significance

Reported here is a Huisgen [3+2] cycloaddition (‘click’ chemistry) of azides with ynamides mediated by Cu(I). It is proposed that this leads to a vinyl copper intermediate A which is trapped in situ by external electrophiles to highly substituted triazoles in fair to good yields. In the absence of electrophile, the ynamine triazole B was isolated as a significant side product resulting from reductive elimination. Product B is the major isolated product from reactions of sulfonyl substituted ynamides (J. A. Porco and co-workers Tetrahedron 2006, 62, 6405). Use of a large excess of external electrophiles, such as allyl iodide, diminished the amount of product B. The derived triazoles having two tethered alkene units were subjected to ring-closing metathesis (RCM) with Grubbs second-generation catalyst to afford fused triazoles. A bridged triazole macrocyclic system was also prepared by this combined methodology.