Solvent effect in diastereoselective intramolecular Diels–Alder reactions
2015
Tomberg, Anna | De Cesco, Stéphane | Huot, Mitchell | Moitessier, Nicolas
In the process of improving the synthesis of a novel class of chiral drug scaffolds, first reported in 2010, we observed that the stereochemical outcome of the key chemical transformation appeared to be correlated to the solvophobicity of the reaction medium. Our mechanistic investigations by NMR monitoring of the reaction confirmed the proposed acylation/intermolecular cycloaddition sequence. The computational studies using DFT methods next predicted exo/endo stereoselectivity (4.3:1 in CHCl3, 1.6:1 in H2O) in agreement with the experimental results (3.3:1 in CHCl3, 1:1 in H2O). The observed stereoselectivity was related to the different level of asynchronicity of the diastereomeric transition states. This leads to different solvent stabilization of the cycloaddition transition state of one diastereomer more than the other.
Show more [+] Less [-]AGROVOC Keywords
Bibliographic information
This bibliographic record has been provided by National Agricultural Library