Facile, High‐Yielding Synthesis of 4‐Functionalised 1,2,3‐Triazoles via Amino‐ and Aryloxycarbonylation

Péter Szuroczki,Ágnes Dörnyei,Levente Molnár,László Kollár

doi:10.1002/slct.201903801

Abstract

Abstract4‐Iodo‐1,2,3‐triazoles were synthesised via azide‐alkyne cycloaddition of alkynyl Grignard reagent and benzyl azide followed by iodination reaction. The aminocarbonylation and aryloxycarbonylation of 4‐iodo‐1,2,3‐triazoles were carried out in the presence of various N‐ and O‐nucleophiles, resulting in the corresponding triazole‐based 4‐carboxamides and 4‐esters, respectively. Both high‐yielding reactions were carried out under mild conditions (atmospheric CO pressure, 70 °C).

Highlights

The facile functionalization of heterocycles in homogeneous catalytic reactions[1] or their multistep synthesis is still in the forefront of the investigation of practically important skeletons. 1,2,3-Triazole-based derivatives are among the most investigated ones.[2]
Our synthetic approach is based on the combination of two efficient catalytic reactions, namely, the azide-alkyne (3 + 2) cycloaddition reaction[8,9,10] and the palladium-catalysed aminocarbonylation discovered by Heck (’Heck carbonylation’).[11]
While the ’click’ reaction revolutionized the synthesis of triazoles,[10] the abovementioned aminocarbonylation enabled the synthesis of even hardly available carboxamides

Summary

Introduction

The facile functionalization of heterocycles in homogeneous catalytic reactions[1] or their multistep synthesis is still in the forefront of the investigation of practically important skeletons. 1,2,3-Triazole-based derivatives are among the most investigated ones.[2]. The facile functionalization of heterocycles in homogeneous catalytic reactions[1] or their multistep synthesis is still in the forefront of the investigation of practically important skeletons. 1,2,3-Triazole-based derivatives are among the most investigated ones.[2] Due to our long interest in the synthesis of carboxamides in palladium-catalysed aminocarbonylation,[3,4] and recently in the functionalization of heterocycles,[5] novel synthetic procedures targeting 4-carboxamido-1,2,3-triazoles of high synthetic and biological (pharmaceutical) importance were considered. Our synthetic approach is based on the combination of two efficient catalytic reactions, namely, the azide-alkyne (3 + 2) cycloaddition reaction[8,9,10] and the palladium-catalysed aminocarbonylation discovered by Heck (’Heck carbonylation’).[11] While the ’click’ reaction revolutionized the synthesis of triazoles,[10] the abovementioned aminocarbonylation enabled the synthesis of even hardly available carboxamides. Our approach is based on the application of conventional highyielding reactions as well as the above homogeneous catalytic reaction, carbonylation reactions in the presence of N- and Onucleophiles

Synthesis of 4-Iodotriazoles

Conclusions

Conflict of Interest