Organocatalysts Fold to Generate an Active Site Pocket for the Mannich Reaction
Neuvonen, A., Földes, T., Madarász, Á., Pápai, I., & Pihko, P. (2017). Organocatalysts Fold to Generate an Active Site Pocket for the Mannich Reaction. ACS Catalysis, 7(5), 3284-3294. https://doi.org/10.1021/acscatal.7b00336
Julkaistu sarjassa
ACS CatalysisPäivämäärä
2017Tekijänoikeudet
© 2017 American Chemical Society. This is a final draft version of an article whose final and definitive form has been published by ACS. Published in this repository with the kind permission of the publisher.
Catalysts containing urea, thiourea and tertiary amine groups fold into a three-dimensional organized structure in
solution both in the absence as well as in the presence of substrates or substrate analogues, as indicated by solution NMR and computational
studies. These foldamer catalysts promote Mannich reactions with both aliphatic and aromatic imines and malonate
esters. Hammett plot and secondary kinetic isotope effects provide evidence for the C-C bond forming event as the turnoverlimiting
step of the Mannich reaction. Computational studies suggest two viable pathways for the C-C bond formation step, differing
in the activation modes of the malonate and imine substrates. The results show that the foldamer catalysts may promote C-C
bond formation with an aliphatic substrate bearing a cyclohexyl group by enhanced binding of the substrates by dispersion interactions,
but these interactions are largely absent with a simpler catalyst. Additional control experiments demonstrate the ability of
simple thiourea catalysts to promote competing side reactions with aliphatic substrates, such as reversible covalent binding of the
thiourea sulfur to the imine which deactivates the catalyst, and imine-to-enamine isomerization reactions. In foldamer catalysts, the
nucleophilicity of sulfur is reduced, which prevents catalyst deactivation. The results indicate that the improved catalytic performance
of foldamer catalysts in Mannich reactions may not be due to cooperative effects of intramolecular hydrogen bonds, but
simply due to the presence of the folded structure that provides an active site pocket, accommodating the substrate and at the same
time impeding undesirable side reactions.
...
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American Chemical SocietyISSN Hae Julkaisufoorumista
2155-5435Asiasanat
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https://converis.jyu.fi/converis/portal/detail/Publication/26933800
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