Triazole-Appended Glycohybrid/CuI-Catalyzed C–C Cross-Coupling of Aryl/Heteroaryl Halides with Alkynyl Sugars

Abstract

This report describes a convenient method for the Cu(I)-catalyzed Sonogashira cross-coupling reaction of aryl/heteroaryl halides and alkynyl sugars in the presence of a 1,2,3-triazole-appended glycohybrid as a biocompatible ligand. The Sonogashira cross-coupling products were exclusively formed without the Glaser-Hay homocoupling reaction in the presence of a glycosyl monotriazolyl ligand at 120 °C. However, the Glaser-Hay homocoupling products were obtained at 60–70 °C in the presence of bis-triazolyl-based macrocyclic glycohybrid ligand L8. The glycosyl triazole ligands were synthesized via the CuI/DIPEA-mediated regioselective CuAAC click reaction, and a series of glycohybrids of glucose, mannose, and galactose alkynes including glycosyl rods were developed in good yields. The developed glycohybrids have been well characterized by various spectroscopic techniques, such as nuclear magnetic resonance, high-resolution mass spectrometry, and single-crystal X-ray data of L3. The protocol works well with the heteroaryl and naphthyl halides, and the mechanistic approach leads to CuI/ligand-assisted oxidative coupling. The coupling protocol has notable features, including low catalytic loading, cost-effectiveness, biocompatible nature, and a wide substrate scope.

Multicomponent Click Reaction: An Indispensable Tool for Easy Access of Functionalized 1,2,3‐Triazoles

“…Compounds containing 1,2,3‐triazole are an important class of compound from a biological point of view as well as their use as synthetic precursors in an array of reactions [38–40] . Besides the various triazole‐appended analogues, the glycohybrid triazole analogues are significant in many disciplines, including drug discovery and development, it is essential to develop effective practical synthetic methods that are quick, simple, high‐yielding, novel, and biocompatible [11,41–50] . The Cu(I)‐catalyzed azide‐alkyne cycloaddition (CuAAC)‐tandem MCR methods are currently recognized for providing a robust framework for rapid access to related triazole‐fused or isolated systems during multi‐component reactions [11,51,52] .…”

“…[38][39][40] Besides the various triazole-appended analogues, the glycohybrid triazole analogues are significant in many disciplines, including drug discovery and development, it is essential to develop effective practical synthetic methods that are quick, simple, highyielding, novel, and biocompatible. [11,[41][42][43][44][45][46][47][48][49][50] The Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC)-tandem MCR methods are currently recognized for providing a robust framework for rapid access to related triazole-fused or isolated systems during multi-component reactions. [11,51,52] The Michael addition is one of the alternate approaches for introducing the azido functionality at the β-position of α,β-unsaturated olefinic ester.…”