Capping Strategies for Covalent Template-Directed Synthesis of Linear Oligomers Using CuAAC.
Journal of the American Chemical Society
American Chemical Society
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Ciaccia, M., Núñez-Villanueva, D., & Hunter, C. (2019). Capping Strategies for Covalent Template-Directed Synthesis of Linear Oligomers Using CuAAC.. Journal of the American Chemical Society, 141 (27), 10862-10875. https://doi.org/10.1021/jacs.9b04973
Covalent templating provides an attractive solution to the controlled synthesis of linear oligomers, because a template oligomer can be used to define the precise length and sequence of the product. If the monomer units are attached to the template using kinetically inert covalent bonds, it should be possible to operate at high dilution to favour intramolecular over intermolecular reaction. However, for oligomerisation reactions using copper catalysed azide alkyne cycloaddition (CuAAC) this is not the case. The rate limiting step is formation of an activated copper complex, so any alkyne that is activated by copper reacts rapidly with the nearest available azide. As a result, every time a chain end alkyne is activated, rapid intermolecular reaction takes place with a different oligomer leading to the formation of higher order products. It proved possible to block these intermolecular reactions by adding an excess of an azide capping agent that intercepts the chain end of the growing oligomer on the template. By adjusting the concentration of the capping agent to compete effectively with the unwanted intermolecular reactions without interfering with the desired intramolecular reactions, it was possible to obtain quantitative yields of copy strands from covalent template-directed oligomerisation reactions. Remarkably the capping agent could also be used to control the stereochemistry of the duplex formed in the templated oligomerisation reaction to give exclusively the antiparallel product.
Copper, Azides, Alkynes, Dimerization, Kinetics, Catalysis, Polymerization, Cycloaddition Reaction
ERC-2012-AdG 320539-duplex, Herchel Smith Fund
European Research Council (320539)
External DOI: https://doi.org/10.1021/jacs.9b04973
This record's URL: https://www.repository.cam.ac.uk/handle/1810/293824
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