Development of a L‐Tryptophan‐Based Ligand for Regioselective Copper Catalyzed N²‐Arylation of 1,2,3‐Triazoles

Abstract

2‐aryl‐1,2,3‐triazoles are important compounds that find applications in Medicinal chemistry, diagnostics, catalysis and others. However, only few methodologies for their preparation is found in the literature. The development of a post cycloaddition N2 selective arylation towards these compounds would benefit from a more convergent strategy. In the present communication, the development of a new tryptophan‐based ligand allowed the selective arylation of the N2‐position of 1,2,3‐triazoles using recyclable CuFe2O4 nanoparticles. This method was efficient in furnishing N2‐arylated and heteroarylated 1,2,3‐triazoles in good yields and excellent N2‐selectivity. The methodology developed found application in the synthesis of the 2‐aryl‐1,2,3‐triazoyl fragment of the drug suvorexant (Belsomra®).

General Synthesis of Tri-Carbo-Substituted N2-Aryl-1,2,3-triazoles via Cu-Catalyzed Annulation of Azirines with Aryldiazonium Salts

“…1,2,3-Triazoles are prevalent functional compounds in medicinal and materials chemistry. , Among them, N 2 -aryl-1,2,3-triazoles are important structural scaffolds found in numerous biologically active molecules in drug discovery, as exemplified in the orexin receptor antagonists, suvorexant, nemorexant, and seltorexant, for treating insomnia. Transition-metal-catalyzed N-arylations have long been employed as the conventional methods to access the target N 2 -aryl-1,2,3-triazoles, but the concomitant formations of N 1 -aryl regioisomeric side products are generally inevitable. Alternatively, annulation reactions using various synthetic synthons are the reliable strategies to deliver N 2 -aryl-1,2,3 triazoles in regiospecific manners. , In this context, annulation reactions of nitrogen-based synthons with aryldiazonium salts have emerged as promising approaches to synthesize N 2 -aryl-1,2,3-triazoles thanks to the convenient preparations and broad scope of aryldiazonium salts .…”