Browse
Submit Data
Databases
API
Help

Dataset Information

32 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Kinetic Resolution of Cyclic Secondary Azides, Using an Enantioselective Copper-Catalyzed Azide-Alkyne Cycloaddition.

ABSTRACT: An enantioselective copper-catalyzed azide-alkyne cycloaddition (E-CuAAC) is reported by kinetic resolution. Chiral triazoles were isolated in high yield with limiting alkyne (up to 97:3 enantiomeric ratio (er)). A range of substrates were tolerated (>30 examples), and the reaction was scaled to >1 g. The er of a triazole product could be enhanced by recrystallization and the recovered scalemic azide could be racemized and recycled. Recycling the azide allows efficient use of the undesired azide enantiomer.

SUBMITTER: Alexander JR

PROVIDER: S-EPMC6631410 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Kinetic Resolution of Cyclic Secondary Azides, Using an Enantioselective Copper-Catalyzed Azide-Alkyne Cycloaddition.

Alexander Juliana R JR Ott Amy A AA Liu En-Chih EC Topczewski Joseph J JJ

Organic letters 20190522 11

An enantioselective copper-catalyzed azide-alkyne cycloaddition (E-CuAAC) is reported by kinetic resolution. Chiral triazoles were isolated in high yield with limiting alkyne (up to 97:3 enantiomeric ratio (er)). A range of substrates were tolerated (>30 examples), and the reaction was scaled to >1 g. The er of a triazole product could be enhanced by recrystallization and the recovered scalemic azide could be racemized and recycled. Recycling the azide allows efficient use of the undesired azide ...[more]

PMID: 31117717

Similar Datasets

Enantioselective Copper Catalyzed Alkyne-Azide Cycloaddition by Dynamic Kinetic Resolution.

Project description:The copper(I) catalyzed alkyne-azide cycloaddition (CuAAC), a click reaction, is one of the most powerful catalytic reactions developed during the last two decades. Conducting CuAAC enantioselectively would add a third dimension to this reaction and would enable the direct synthesis of α-chiral triazoles. Doing so is demanding because the two precursors have linear geometries, and the triazole product is a flat heterocycle. Designing a chiral catalyst is further complicated by the complex mechanism of CuAAC. We report an enantioselective CuAAC (E-CuAAC), enabled by dynamic kinetic resolution (DKR). The E-CuAAC is high yielding and affords up to 99:1 er. The E-CuAAC can directly generate α-chiral triazoles in a complex molecular environment.

| S-EPMC6594181 | biostudies-literature

Enantioselective Nickel-Catalyzed Alkyne-Azide Cycloaddition by Dynamic Kinetic Resolution.

Project description:The triazole heterocycle has been widely adopted as an isostere for the amide bond. Many native amides are α-chiral, being derived from amino acids. This makes α-N-chiral triazoles attractive building blocks. This report describes the first enantioselective triazole synthesis that proceeds via nickel-catalyzed alkyne-azide cycloaddition (NiAAC). This dynamic kinetic resolution is enabled by a spontaneous [3,3]-sigmatropic rearrangement of the allylic azide. The 1,4,5-trisubstituted triazole products, derived from internal alkynes, are complementary to those commonly obtained by the related CuAAC reaction. Initial mechanistic experiments indicate that the NiAAC reaction proceeds through a monometallic Ni complex, which is distinct from the CuAAC manifold.

| S-EPMC8130861 | biostudies-literature

Electrochemically protected copper(I)-catalyzed azide-alkyne cycloaddition.

Project description:The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction has found broad application in myriad fields. For the most demanding applications that require high yields at low substrate concentrations, highly active but air-sensitive copper complexes must be used. We describe here the use of an electrochemical potential to maintain catalysts in the active Cu(I) oxidation state in the presence of air. This simple procedure efficiently achieves excellent yields of CuAAC products from both small-molecule and protein substrates without the use of potentially damaging chemical reducing agents. A new water-soluble carboxylated version of the popular tris(benzyltriazolylmethyl)amine (TBTA) ligand is also described. Cyclic voltammetry revealed reversible or quasi-reversible electrochemical redox behavior of copper complexes of the TBTA derivative (2; E(1/2)=60 mV vs. Ag/AgCl), sulfonated bathophenanthroline (3; E(1/2)=-60 mV), and sulfonated tris(benzimidazoylmethyl)amine (4; E(1/2) approximately -70 mV), and showed catalytic turnover to be rapid relative to the voltammetry time scale. Under the influence of a -200 mV potential that was established by using a reticulated vitreous carbon working electrode, CuSO4 and 3 formed a superior catalyst. Electrochemically protected bioconjugations in air were performed by using bacteriophage Qbeta that was derivatized with azide moieties at surface lysine residues. Complete derivatization of more than 600 reactive sites per particle was demonstrated within 12 h of electrolysis with substoichiometric quantities of Cu3.

| S-EPMC3574790 | biostudies-literature

Solvent-free copper-catalyzed azide-alkyne cycloaddition under mechanochemical activation.

Project description:The ball-mill-based mechanochemical activation of metallic copper powder facilitates solvent-free alkyne-azide click reactions (CuAAC). All parameters that affect reaction rate (i.e., milling time, revolutions/min, size and milling ball number) have been optimized. This new, efficient, facile and eco-friendly procedure has been tested on a number of different substrates and in all cases afforded the corresponding 1,4-disubstituted 1,2,3-triazole derivatives in high yields and purities. The final compounds were isolated in almost quantitative overall yields after simple filtration, making this procedure facile and rapid. The optimized CuAAC protocol was efficiently applied even with bulky functionalized ?-cyclodextrins (?-CD) and scaled-up to 10 g of isolated product.

| S-EPMC6272186 | biostudies-other

Conditional Copper-Catalyzed Azide-Alkyne Cycloaddition by Catalyst Encapsulation.

Project description:Supramolecular encapsulation is known to alter chemical properties of guest molecules. We have applied this strategy of molecular encapsulation to temporally control the catalytic activity of a stable copper(I)-carbene catalyst. Encapsulation of the copper(I)-carbene catalyst by the supramolecular host cucurbit[7]uril (CB[7]) resulted in the complete inactivation of a copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. The addition of a chemical signal achieved the near instantaneous activation of the catalyst, by releasing the catalyst from the inhibited CB[7] catalyst complex. To broaden the scope of our on-demand CuAAC reaction, we demonstrated the protein labeling of vinculin with the copper(I)-carbene catalyst, to inhibit its activity by encapsulation with CB[7] and to initiate labeling at any moment by adding a specific signal molecule. Ultimately, this strategy allows for temporal control over copper-catalyzed click chemistry, on small molecules as well as protein targets.

| S-EPMC7318279 | biostudies-literature

Relative performance of alkynes in copper-catalyzed azide-alkyne cycloaddition.

Project description:Copper-catalyzed azide-alkyne cycloaddition (CuAAC) has found numerous applications in a variety of fields. We report here only modest differences in the reactivity of various classes of terminal alkynes under typical bioconjugative and preparative organic conditions. Propargyl compounds represent an excellent combination of azide reactivity, ease of installation, and cost. Electronically activated propiolamides are slightly more reactive, at the expense of increased propensity for Michael addition. Certain alkynes, including tertiary propargyl carbamates, are not suitable for bioconjugation due to copper-induced fragmentation. A fluorogenic probe based on such reactivity is available in one step from rhodamine 110 and can be useful for optimization of CuAAC conditions.

| S-EPMC4170714 | biostudies-literature

Analysis and optimization of copper-catalyzed azide-alkyne cycloaddition for bioconjugation.

Project description: Not available

| S-EPMC3410708 | biostudies-literature

Towards understanding the kinetic behaviour and limitations in photo-induced copper(i) catalyzed azide-alkyne cycloaddition (CuAAC) reactions.

Project description:The kinetic behaviour of the photo-induced copper(i) catalyzed azide-alkyne cycloaddition (CuAAC) reaction was studied in detail using real-time Fourier transform infrared (FTIR) spectroscopy on both a solvent-based monofunctional and a neat polymer network forming system. The results in the solvent-based system showed near first-order kinetics on copper and photoinitiator concentrations up to a threshold value in which the kinetics switch to zeroth-order. This kinetic shift shows that the photo-CuAAC reaction is not susceptible from side reactions such as copper disproportionation, copper(i) reduction, and radical termination at the early stages of the reaction. The overall reaction rate and conversion is highly dependent on the initial concentrations of photoinitiator and copper(ii) as well as their relative ratios. The conversion was decreased when an excess of photoinitiator was utilized compared to its threshold value. Interestingly, the reaction showed an induction period at relatively low intensities. The induction period is decreased by increasing light intensity and photoinitiator concentration. The reaction trends and limitations were further observed in a solventless polymer network forming system, exhibiting a similar copper and photoinitiator threshold behaviour.

| S-EPMC5074343 | biostudies-literature

Photoinitiated Copper(I) Catalyzed Azide-Alkyne Cycloaddition Reaction for Ion Conductive Networks.

Project description:The photoinitiated copper(I) catalyzed azide-alkyne cycloaddition (photo-CuAAC) is a 'click' reaction that enables spatially and temporally controlled polymerizations. The solvent-less photopolymerization of multi-functional azide and cationic alkyne monomers results in the rapid formation of a charged polymer network. Full conversion of these monomers is achieved within 30 minutes under mild, blue-light irradiation conditions (470 nm light at 30 mW/cm2). The modulus of the material is readily tuned by controlling the ratio of di- and tri-functional alkyne monomers. Facile exchange of the hydrophobic bistriflimide counterion for a hydroxide anion yields an ion conductive polymer network with photopatternable charged regions. The spatiotemporal nature of the ionic photo-CuAAC reaction coupled with the chemical stability and mechanical flexibility suggests this chemistry is a facile and novel approach for ion-containing material synthesis (e.g., alkaline fuel cells components).

| S-EPMC7451218 | biostudies-literature

Kinetics of bulk photo-initiated copper(i)-catalyzed azide-alkyne cycloaddition (CuAAC) polymerizations.

Project description:Photoinitiation of polymerizations based on the copper(i)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction enables spatio-temporal control and the formation of mechanically robust, highly glassy photopolymers. Here, we investigated several critical factors influencing photo-CuAAC polymerization kinetics via systematic variation of reaction conditions such as the physicochemical nature of the monomers; the copper salt and photoinitiator types and concentrations; light intensity; exposure time and solvent content. Real time Fourier transform infrared spectroscopy (FTIR) was used to monitor the polymerization kinetics in situ. Six different di-functional azide monomers and four different tri-functional alkyne monomers containing either aliphatic, aromatic, ether and/or carbamate substituents were synthesized and polymerized. Replacing carbamate structures with ether moieties in the monomers enabled an increase in conversion from 65% to 90% under similar irradiation conditions. The carbamate results in stiffer monomers and higher viscosity mixtures indicating that chain mobility and diffusion are key factors that determine the CuAAC network formation kinetics. Photoinitiation rates were manipulated by altering various aspects of the photo-reduction step; ultimately, a loading above 3 mol% per functional group for both the copper catalyst and the photoinitiator showed little or no rate dependence on concentration while a loading below 3 mol% exhibited 1st order rate dependence. Furthermore, a photoinitiating system consisting of camphorquinone resulted in 60% conversion in the dark after only 1 minute of 75 mW cm-2 light exposure at 400-500 nm, highlighting a unique characteristic of the CuAAC photopolymerization enabled by the combination of the copper(i)'s catalytic lifetime and the nature of the step-growth polymerization.

| S-EPMC4946250 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data