Multi-Component Reaction for the Preparation of 1,5-Disubstituted 1,2,3-Triazoles by In-Situ Generation of Azides and Nickel-Catalyzed Azide-Alkyne Cycloaddition

Virgyl Camberlein (1) , Nicolas Kraupner (1) , Nour Bou Karroum (1) , Emmanuelle Lipka (2) , Rebecca Deprez-Poulain (1) , Benoit Deprez (1) , Damien Bosc (1)

1 M2SV - Médicaments et molécules pour agir sur les Systèmes Vivants - U 1177
2 RID-AGE - Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167

An efficient one-pot procedure combining bromide conversion into azide followed by NiAAC for the preparation of 1,5-disubstituted 1,2,3-triazoles has been developed. This procedure prevents the use of isolated azides, which are insufficiently commercially available and could be potentially unstable and difficult to handle. Moreover, this one-pot method tolerates a broad range of functional moieties including ester, carbamate or alcohol. Diverse 1,5-disubstituted 1,2,3-triazoles can be obtained from functionalized aryl and alkyl alkynes and bromides with modest to excellent yields and regioselectivities. This procedure will enable the synthesis of libraries of functionalizable 1,5disubstituted 1,2,3-triazoles particularly helpful for diverse applications such as medicinal chemistry and chemical biology purposes.

Mots clés: click chemistry; molecular diversity; multicomponent reactions; regioselectivity; synthetic methods

Domaines: Chimie organique

Virgyl Camberlein, Nicolas Kraupner, Nour Bou Karroum, Emmanuelle Lipka, Rebecca Deprez-Poulain, et al.. Multi-Component Reaction for the Preparation of 1,5-Disubstituted 1,2,3-Triazoles by In-Situ Generation of Azides and Nickel-Catalyzed Azide-Alkyne Cycloaddition. Tetrahedron Letters, In press, ⟨10.1016/j.tetlet.2021.153131⟩. ⟨hal-03207833⟩