Click Chemistry Under Microwave or Ultrasound Irradiation

Alessandro      Barge; Silvia      Tagliapietra; Arianna      Binello; Giancarlo      Cravotto

doi:10.2174/138527211793979826

Abstract

The copper-catalyzed azide-alkyne cycloaddition (CuAAC) is generally recognized as the most striking example of “click reaction”. CuAAC fit so well into Sharpless definition that it became almost synonymous with “click chemistry” itself. The most common catalyst systems employ Cu(II) salt in the presence of a reducing agent (i.e. sodium ascorbate) to generate the required Cu(I) catalyst in situ or as an alternative the comproportionation of Cu(II)/Cu(0) species. Although, Cu(I) catalyzes the reaction with a rate enhancement of ∼107 even in the absence of ligands and provides a clean and selective conversion to the 1,4-substituted triazoles, some bulky and scantily reactive substrates still require long reaction times and often few side products are formed. Outstanding results have been achieved by performing CuAAC under microwave (MW) irradiation. Several authors described excellent yields, high purity and short reaction times. In few cases also power ultrasound (US) accelerated the reaction, especially when heterogeneous catalysts or metallic copper are employed. The aim of this review is to summarize and highlight the huge advantages offered by MW- and US-promoted CuAAC. In the growing scenario of innovative synthetic strategies, we intend to emphasize the complementary role played by these non-conventional energy sources and click chemistry to achieve process intensification in organic synthesis.

Keywords: Click chemistry, microwave, ultrasound, organic synthesis, green chemistry, Ultrasound Irradiation, copper-catalyzed azide-alkyne cycloaddition, click re-action, 1,4-substituted triazoles, microwave (MW) irradiation, 1,3-dipolar Huisgen cycloaddition, macro-cyclic structures, oxidation, reduction, hydrolysis, peptidomimet-ics, bioconjugation, combinato-rial drug discovery, nucleosides, oligonucleotides, bioisosteres, active moieties, bioorthogonal reac-tions, carbohydrate-based drug discovery, glycobiology, rotaxanes, catenane, sonochemical conditions, Peptides, Liskamp's group, bis-propinoxybenzoic acid, azidoacid, azidopep-tide, cyclic-RGD (Arg-Gly-Asp tripeptide), non-hydrolysable isoster, Fmoc-protected small peptidomimetics, 1,3 dipolar cycloaddition, acetylenic amide, silica-gel chromatography, N-Boc-amino-alkyne, Boc cleavage, tissue engineering, novel bio-materials, dipeptide azido-phenylalanyl-alanyl-propargyl, mer-capto, hydroxy, carboxylic groups, nucleic acid, triplex-forming, oligonucleotides (TFOs), peptide nucleic, DNA, Saccharide Conjugation, Oligo- and Polysaccharides, Glycosilated aminoacids, linear oligomer, cyclic dimer, ethynylpyrazinone, azido saccharide, azido-functionalized, phosphoramidate bonds, DNA based glycoclusters, Propargylated pentaerythrityl phosphodiester oligomers, bis-propargylated pentaerythritol-based phosphoramidite, ascorbic, Glycodendrimers, heptavalent glycocy-clodexrins, propargyl, thiopropargyl mannose, ascorbic acid catalytic system, Heptakis-azido-cyclodextrin, gold nanoparticles, poli-azido gold, 1'azido-2',3',5',tri-O-acetylribose, ruthenium-catalyzed, Ru-catalyzed click reactions, Bronsted acid, 2-azido-4,4-bis-hydroxymethylcyclopentanole, carbanucleosides, tetrakis(acetonitrile)copper hexafluorophos-phate ([Cu(CH3CN)4]PF6), imidazoline(mesythyl) copper bro-mide (Imes)CuBr, enzymatic depolymerization, thymidine dimer, in situ, Miscellaneous, [1,5-a]azocine skeleton, a potent antileukemic, tubu-lin polymerization, stereochemistry, diastereoisomer, organic azides, Biginelli's multicomponent reaction, triazolyl-quinolones