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

31 May 2025, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

A ruthenium-catalysed 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 modelling 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.

Keywords

ruthenium
selenium
cycloaddition
nitrogen heterocycles
computational chemistry

Supplementary materials

Title
Description
Actions
Title
Supporting Information
Description
Synthetic procedures, characterisation data, additional computational details, NMR traces of novel compounds
Actions

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.