Solvent effect in diastereoselective intramolecular Diels-Alder reactions

被引：10

作者：

Tomberg, Anna ^{[1
]}

De Cesco, Stephane ^{[1
]}

Huot, Mitchell ^{[1
]}

Moitessier, Nicolas ^{[1
]}

机构：

[1] McGill Univ, Dept Chem, Montreal, PQ H3A 0B8, Canada

来源：

TETRAHEDRON LETTERS | 2015年 / 56卷 / 49期

基金：

加拿大自然科学与工程研究理事会;

关键词：

IMDA; Solvent effect; DFT; Diastereoselectivity; DESIGN; STEREOSELECTIVITY; SELECTIVITIES;

D O I：

10.1016/j.tetlet.2015.10.086

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

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. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：6852 / 6856

页数：5

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