Journal
CHEMISTRY-A EUROPEAN JOURNAL
Volume 19, Issue 42, Pages 14286-14295Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.201200832
Keywords
asymmetric catalysis; cinchona alkaloids; Conia-ene reaction; quantum mechanical calculations; reaction mechanism
Categories
Funding
- EPSRC
- Oxford University Press John Fell fund
- European Community (IEF) [PIEF-GA-2009-254068]
- Spanish Ministerio de Educacion (MEC)
- EPSRC [EP/J003921/1] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [EP/J003921/1] Funding Source: researchfish
Ask authors/readers for more resources
The enantioselective Conia-ene cyclization of alkyne-tethered -ketoesters is efficiently catalyzed by the combination of cinchona-derived amino-urea pre-catalysts and copper(I) salts. The reaction scope is broad and a series of substrates can be efficiently cyclized with high yields and enantioselectivities. Herein, we present a detailed mechanistic study based on experimental considerations and quantum mechanical calculations. Several variables, such as the nature of the organic pre-catalyst and the metal-ion source, have been thoroughly investigated. Kinetic studies, as well as kinetic isotope effects and deuterium labeling experiments have been used to gain further insights into the mechanism and prove the cooperative nature of the catalytic system. Our studies suggest that the rate-limiting step for the reaction involves the -ketoester deprotonation and that the active species responsible for the enantiodeterming step is monomeric in amino-urea pre-catalyst. Computational studies provide a quantitative understanding of the observed stereoinduction and identify hydrogen bonding from the urea group as a crucial factor in determining the observed enantioselectivity.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available