Record Details

Mechanistic Insights on Organocatalytic Enantioselective Decarboxylative Protonation by Epicinchona-Thiourea Hybrid Derivatives

DSpace at IIT Bombay

View Archive Info
 
 
Field Value
 
Title Mechanistic Insights on Organocatalytic Enantioselective Decarboxylative Protonation by Epicinchona-Thiourea Hybrid Derivatives
 
Creator SENGUPTA, A
SUNOJ, RB
 
Subject BIFUNCTIONAL CINCHONA ORGANOCATALYSTS
MOLECULAR-DYNAMICS SIMULATIONS
DENSITY-FUNCTIONAL THEORY
HYDROGEN-BOND DONORS
ASYMMETRIC CATALYSIS
MICHAEL REACTION
COMBINED NMR
METAL-FREE
ALKALOIDS
SYSTEMS
 
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.
 
Publisher AMER CHEMICAL SOC
 
Date 2014-10-15T08:44:35Z
2014-10-15T08:44:35Z
2012
 
Type Article
 
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
 
Language en