Selective Formation of 1,4-Disubstituted Triazoles from Ruthenium-Catalyzed Cycloaddition of Terminal Alkynes and Organic Azides: Scope and Reaction Mechanism

The catalytic activity of a series of ruthenium complexes lacking cyclopentadienyl ligands has been evaluated for the cycloaddition of terminal alkynes and azides to give selectively 1,4-disubstituted 1,2,3-triazoles. The complex RuH­(η²-BH₄)­(CO)­(PCy₃)₂ was found to be an effective catalyst for the cycloaddition reactions. In the presence of RuH­(η²-BH₄)­(CO)­(PCy₃)₂, primary and secondary azides reacted with a range of terminal alkynes containing various functionalities to selectively produce 1,4-disubstituted 1,2,3-triazoles. The ruthenium-catalyzed azide–alkyne cycloaddition appears to proceed via a Ru–acetylide species as the key intermediate, which undergoes formal cycloaddition with an azide to give a ruthenium triazolide complex. The 1,4-disubstituted 1,2,3-triazole product is generated by metathesis of the triazolide complex with a terminal alkyne. In support of the reaction mechanism, the acetylide complex Ru­(CCCMe₃)₂(CO)­(PPh₃)₃ reacts cleanly with benzyl azide to give a ruthenium triazolide complex, which reacts with excess tert-butylacetylene in the presence of PPh₃ to give 4-tert-butyl-1-benzyl-1,2,3-triazole and the diacetylide complex Ru­(CCCMe₃)₂(CO)­(PPh₃)₃. The mechanism is also supported by DFT calculations.