Mechanistic Insights on Organocatalytic Enantioselective Decarboxylative Protonation by Epicinchona-Thiourea Hybrid Derivatives
DSpace at IIT Bombay
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Title |
Mechanistic Insights on Organocatalytic Enantioselective Decarboxylative Protonation by Epicinchona-Thiourea Hybrid Derivatives
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Creator |
SENGUPTA, A
SUNOJ, RB |
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Subject |
BIFUNCTIONAL CINCHONA ORGANOCATALYSTS
MOLECULAR-DYNAMICS SIMULATIONS DENSITY-FUNCTIONAL THEORY HYDROGEN-BOND DONORS ASYMMETRIC CATALYSIS MICHAEL REACTION COMBINED NMR METAL-FREE ALKALOIDS SYSTEMS |
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Description |
Mechanism and the origin of enantioselectivity in the decarboxylative protonation of alpha-amino malonate hemiester promoted by epicinchona-thiourea hybrid organocatalyst is established by using the DFT(M06-2X/6-311+G**//ONIOM2) computational methods. The origin of stereoselectivity rendered by this hybrid bifunctional catalyst in asymmetric protonation is investigated for the first time using suitable transition-state models. A detailed conformational analysis of N-[3,5-bis(trifluoromethyl)]phenylthiourea-based epicinchonidine reveals the potential for a bifunctional mode of activation of the substrate a-amino malonate hemiester through hydrogen bonding. Six different conformer families differing in characteristic dihedral angles are identified within a range of 16 kcal/mol with respect to the lowest energy conformer. Different likely mechanistic pathways obtained through detailed analysis of the transition states and intermediates are compared. It is identified that in the preferred pathway, the decarboxylation is followed by a direct proton transfer from the chiral quinuclidinium moiety to the enolate carbon as opposed to a conventional protonation at the enolate oxygen followed by a keto-enol tautomerization. The factors responsible for high levels of observed stereoselectivity are traced to interesting hydrogen bonding interactions offered by the thiourea-cinchona bifunctional framework. The predicted stereoselectivities using computed Gibbs free energies of diastereomeric transition states are in fair agreement with the experimental stereoselectivities.
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Publisher |
AMER CHEMICAL SOC
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Date |
2014-10-15T08:44:35Z
2014-10-15T08:44:35Z 2012 |
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Type |
Article
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Identifier |
JOURNAL OF ORGANIC CHEMISTRY, 77(23)10525-10536
http://dx.doi.org/10.1021/jo301483p http://dspace.library.iitb.ac.in/jspui/handle/100/14715 |
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Language |
en
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