Synthesis of 3-perfluoroalkyl-substituted 1,2,4-triazinones through copper(I)-catalyzed interrupted click reaction

A Cu-catalyzed interrupted click reaction for the synthesis of 3-perfluoroalkyl-substituted 1,2,4-triazinones is developed. The reaction between the terminal alkynes with azides and pentafluoropropionic or heptafluorobutyric anhydride proceeds smoothly to afford the corresponding pentafluoroethylated or heptafluoropropyled products in good yields. This protocol is applicable to various types of substrates including arylacetylenes and aliphatic azides having electron-rich and electron-deficient groups. The broad substrate scope and functional group tolerance of the reaction makes this approach a practical method for the synthesis of valuable 3-perfluoroalkyl-substituted 1,2,4-triazinones. Some of the title compounds showed fungicidal activity against cucumber downy mildew (CDM).     

Synthesis of modified triazole nucleosides possessing one or two base moieties via a click chemistry approach

Copper-catalyzed 1,3-dipolar cycloaddition of propargyl and azidoethyl thymine and adenine derivatives afforded triazole nucleosides bearing one or two base moieties. A catalytic role of the adenine nucleus was observed and is explained through copper-adenine coordination in the intermediate copper acetylide-azide complex. The antioxidant activity of the obtained cycloadducts was tested.     

Synthesis and DSSC application of novel dendrimers with benzothiazole and triazole units

Synthesis of novel dendrimers with benzothiazole as surface group and triazole as branching unit is achieved through click chemistry. The presence of more number of benzothiazole and triazole units increases the molar absorption coefficient and alters the fluorescence as well as electrochemical behaviors in the dendrimers. Dye-sensitized solar cell (DSSC) studies reveal that dendrimers with more number of benzothiazole and triazole groups exhibit better current generating capacity than the dendrimers with lesser number of benzothiazole and triazole groups. Dendrimer 2b shows the maximum current conversion efficiency (η) of 7.1%.     

A novel green synthesis of α/β-amino acid functionalized pyrimidinone peptidomimetics using triazole ligation through click-multi-component reactions

An innovative synthetic pathway for the preparation of a new series of triazole-decorated dihydropyrimidinone peptidomimetics with skeletal α or β-amino acid residue is reported. The protocol involves two synthetic steps with an initial solvent-free and catalyst-free synthesis of propargylated dihydropyrimidinone precursors using Biginelli condensations. The subsequent cycloaddition reactions of pyrimidinone alkynes with small peptide like azides prepared from Ugi or alternate Mannich type multi-component reactions afforded the triazole decorated pyrimidinone peptide conjugates in excellent yield with high regio and stereospecificities. In total, a scaffold diversity contains 11 new pyrimidinone alkynes and 18 new pyrimidinone peptidomimetics were introduced into the chemical space.     

Synthesis of new copper(I)-complexed rotaxanes via click chemistry

The Cu(I)-catalyzed dipolar cycloaddition of azides and terminal alkynes (‘click’ chemistry) has been used as a mild and efficient stoppering reaction for the preparation of new copper(I)-complexed rotaxanes.     

Copper(I) oxide and benzoic acid ‘on water’: a highly practical and efficient catalytic system for copper(I)-catalyzed azide-alkyne cycloaddition

A simple combination of Cu₂O and PhCO₂H ‘on H₂O’ has been developed as a highly practical and efficient catalytic system for copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). It not only provides a further evidence for the strategy of carboxylic acids-promoted CuAAC, but also offers significant advantages to CuAAC because Cu₂O is one of the most stable and cheapest Cu(I) sources; PhCO₂H is one of the structurally simplest bidentate ligands; and water is the most ‘green’ solvent.     

Synthesis of novel aromatic ether polymers containing perfluorocyclobutyl and triazole units via click chemistry

The synthesis and characterization of a novel class of linear aromatic ether polymers containing perfluorocyclobutyl and triazole unites is described. These polymers were prepared from the click chemistry (the copper-catalyzed Huisgen's 1,3-dipolar cycloaddition) of new monomer 1,2-bis(4-azidomethylphenoxy) perfluorocyclobutane and bisethynyl compounds.     

Synthesis and properties of triazole bridged BODIPY-conjugates

A series of triazole bridged BODIPY-conjugates were synthesized under click reaction conditions. The 3-azido BODIPY was generated in situ by treating 3-bromo BODIPY with NaN₃ in CH₃CN at room temperature for 60 min and reacted with appropriate ethynyl containing chromophore/redox active unit, such as ferrocene, BODIPY, Zn(II) porphyrin, 21,23-dithiaporphyrin, BF₂-smaragdyrin in the presence of CuI/DIPEA in THF/CH₃CN solvent. The conjugates were purified by column chromatography and obtained pure compounds in 45–50% yields. The conjugates were characterized by HR-MS, 1D, 2D, ¹⁹F and ¹¹B NMR and X-ray crystallography for BODIPY-ferrocene conjugate. Absorption and electrochemical studies showed features of both the moieties present in the conjugates and also support interaction between the two moieties in the conjugates. The fluorescence studies supported an efficient energy transfer from BODIPY unit to BF₂-smaragdyrin unit in BODIPY–BF₂-smaragdyrin conjugate but the energy transfer was not efficient in BODIPY–Zn(II) porphyrin and BODIPY–21,23-dithiaporphyrin conjugates.     

Click chemistry to functionalise peptidomimetics

Sharpless modified Huisgen’s [2+3] cycloaddition of azide and acetylenic derivatives was employed as an efficient and simple method to conjugate azabicycloalkane amino acids, mimics of a homoSer-Pro dipeptide, with biologically relevant partners.     

Nucleophilic 5-endo-trig cyclization of 2-(trifluoromethyl)allylic metal enolates and enamides: Synthesis of tetrahydrofurans and pyrrolidines bearing exo-difluoromethylene units

Ketones and imines bearing a 2-(trifluoromethyl)allylic moiety successfully underwent nucleophilic 5-endo-trig cyclization via their metal enolates and enamides. O- or N-Cyclization proceeded exclusively in each case to afford the corresponding five-membered heterocycles with both exo-difluoromethylene and exo-alkylidene units. On treatment with potassium hexamethyldisilazide (KHMDS) or lithium diisopropylamide (LDA), 2-(trifluoromethyl)allylic ketones or imines provided the corresponding tetrahydrofurans or pyrrolidines bearing a Z-alkylidene group with perfect or substantial stereoselectivity, respectively.     

Microwave-assisted synthesis of fused heterocycles incorporating trifluoromethyl moiety

4,4,4-Trifluoro-1-(thien-2-yl)butane-1,3-dione (1) reacts with 5-aminopyrazole, 1,2,4-aminotriazole and 2-aminobenzimidazole derivatives, in the presence of triethylorthoformate under pressurized microwave irradiation to afford the corresponding trifluoromethyl derivatives of pyrazolo[1,5-a]pyrimidine, 1,2,4-triazolo[1,5-a]pyrimidine, and pyrimido[1,2-a]benzimidazoles. Also, compound 1 couples readily with azole diazonium salts to give pyrazolo[5,1-c]triazine, benzimidazo[5,1-c]1,2,4-triazine, and triazolo[3,4-c]1,2,4-triazine derivatives incorporating trifluoromethyl group.     

Combination of click chemistry and sulfonamides to develop three-armed triazole compounds

Fragment-based drug discovery is a valuable tool in hit identification, as well as the combination of different small fragments showing a minimal binding activity against biological receptors or enzymes to give merged hits. A high number of fragments on the same scaffold improve the probability to find a candidate showing single- or multi-target affinities. A rapid and versatile approach for synthesizing libraries of densely fragment-functionalized scaffolds is reported. Many fragments were assembled in few steps around a triazole ring starting from amino alcohols and other readily available building blocks. A binding assay against integrin α_vβ₃ was used as a test-bed in order to demonstrate the potential of such an approach in hit discovery strategies.     

Synthesis of a Schiff’s base chiral ligand with a trifluoromethyl carbinol moiety

A Schiff’s base ligand with a trifluoromethyl carbinol moiety was synthesized, and a structure of the active complex for asymmetric induction on the reaction of diethylzinc with aldehydes is proposed.     

An efficient green diversity oriented synthesis of pyrimidinone and indole appended macrocyclic peptidomimetics

A concise protocol for the synthesis of pyrimidinone/indole functionalized hybrid peptide macrocycles with varying ring size is described. The precursors of the macrocycles were obtained from the post reaction modification of multicomponent reaction products and were cyclized via copper (I) catalyzed [3?+?2] azide-alkyne cycloaddition. The macrocycles showed excellent inhibitory property towards CDK2 protein which is responsible for a variety of cancers and were also showed excellent cytotoxicity against human breast cancer cell line MCF-7.     

A fluorescent sensor for Hg and Ag functions as a molecular switch based on click-generated triazole moiety

The novel (S)-BINOL-based sensor 1 incorporating triazole moieties could be obtained by click reaction. The results show that 1 can exhibit excellent fluorescence response behaviors toward Hg²⁺ (selective switching-off) and Ag⁺ (selective switching-on) without interference from other metal ions, which functions as a molecular switch. This work can expand the application of click reaction in design and synthesis of the novel fluorescence sensor molecules.     

N-Sulfonyl acetylketenimine as a highly reactive intermediate for synthesis of N-Aroylsulfonamides

A highly reactive intermediate N-sulfonyl acetylketenimine was generated from an ynone-participated CuAAC/ring-opening method. Its unique structure allowed it to react with aryl carboxylic acids to give N-aroylsulfonamides via a novel Mumm-type rearrangement.     

Synthesis of N-unsubstituted 1,2,3-triazoles via aerobic oxidative N-dealkylation using copper(II) acetate

A copper-catalyzed aerobic oxidative CN bond cleavage reaction was developed for the synthesis of 4-substituted-NH-1,2,3-triazoles. Diverse β-ketotriazoles derivatives, which are the starting materials for the aerobic oxidative CN bond cleavage reaction, were prepared from nine aryl and seven alkyl alkynes and α-azidoacetophenone by a copper(I)-catalyzed [3 + 2]cycloaddition reaction. The aerobic oxidation of α-(1,2,3-triazol-1-yl)acetophenones using a catalytic amount of copper(II) acetate in the presence oxygen under neutral conditions gave the title compounds in high yield.     

Isostructural Nanocluster Manipulation Reveals Pivotal Role of One Surface Atom in Click Chemistry

Elucidating single-atom effects on the fundamental properties of nanoparticles is challenging because single-atom modifications are typically accompanied by appreciable changes to the overall particle's structure. Herein, we report the synthesis of a [Cu₅₈H₂₀PET₃₆(PPh₃)₄]²⁺ ( Cu₅₈ ; PET: phenylethanethiolate; PPh₃: triphenylphosphine) nanocluster—an atomically precise nanoparticle—that can be transformed into the surface-defective analog [Cu₅₇H₂₀PET₃₆(PPh₃)₄]⁺ ( Cu₅₇ ). Both nanoclusters are virtually identical, with five concentric metal shells, save for one missing surface copper atom in Cu₅₇ . Remarkably, the loss of this single surface atom drastically alters the reactivity of the nanocluster. In contrast to Cu₅₈ , Cu₅₇ shows promising activity for click chemistry, particularly photoinduced [3+2] azide-alkyne cycloaddition (AAC), which is attributed to the active catalytic site in Cu₅₇ after the removal of one surface copper atom. Our study not only presents a unique system for uncovering the effect of a single-surface atom modification on nanoparticle properties but also showcases single-atom surface modification as a powerful means for designing nanoparticle catalysts.     

Synthesis of new azaphthalocyanine dark quencher and evaluation of its quenching efficiency with different fluorophores

New unsymmetrical zinc azaphthalocyanine (AzaPc) was synthesized using statistical condensation of two precursors. Postsynthetic modifications led to incorporation of azide group that efficiently underwent Cu(I)-catalyzed azide/alkyne 1,3-dipolar cycloaddition with terminal alkyne on a solid phase. The modified solid phase was then used for synthesis of oligodeoxyribonucletides labeled with AzaPc. DNA hybridization assays confirmed high quenching efficiency (QE>96%) of zinc AzaPc quencher with six different fluorophores ranging in emission maxima from 517 nm to 701 nm (FAM, HEX, Cy3, Cy3.5, Cy5, and Cy5.5).