Ruthenium-Catalyzed Azide-Selenoalkyne Cycloadditions: A Combined Synthetic–Computational Study into Reaction Scope, Mechanism, and Origins of Regioselectivity

A ruthenium-catalyzed azide–alkyne cycloaddition (RuAAC) reaction involving selenoalkynes is reported for the synthesis of selenium-substituted 1,2,3-triazole products (26 examples, up to 89% yield). The reaction works well with a wide range of alkyl and aryl azides bearing both electron-donating and -withdrawing groups. This contrasts RuAAC reactions using regular terminal and internal alkynes, where aryl azides bearing electron-withdrawing groups are not generally tolerated. The regioselectivity of the cycloaddition is highly dependent on the identity of the non-selenium substituent of the alkyne. This challenges earlier reports on RuAAC reactions involving thioalkynes and questions the perceived understanding of the regioselectivity of these reactions. Computational modeling of the reaction profiles for four alkyne substrates that provided contrasting regioselectivities accurately reproduces the experimental results. The observed regioselectivity is primarily attributed to the relative nucleophilicity of the alkyne carbons upon coordination to ruthenium and an approach is proposed in which reaction regioselectivity may be predicted.