Solvent effect in diastereoselective intramolecular Diels–Alder reactions

Autor:	Mitchell Huot, Anna Tomberg, Stéphane De Cesco, Nicolas Moitessier
Rok vydání:	2015
Předmět:	Acylation Chemistry Stereochemistry Intramolecular force Organic Chemistry Drug Discovery Intermolecular force Diastereomer Stereoselectivity Solvent effects Biochemistry Transition state Cycloaddition
Zdroj:	Tetrahedron Letters. 56:6852-6856
ISSN:	0040-4039
DOI:	10.1016/j.tetlet.2015.10.086
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::1349cd679cc0275b7ad25dff66f36a98 https://doi.org/10.1016/j.tetlet.2015.10.086 Zobrazit plný text záznamu Full Text from ScienceDirect