Carda M, Portoles R, Murga J, Uriel S, Marco JA, Domingo LR, Zaragoza RJ, Roper H
U. P. de Quimica Inorganica y Organica, Universidad Jaume I, E-12080 Castellon, Spain; Departamento de Quimica Organica, Universidad de Valencia, E-46100 Burjassot, Valencia, Spain; and Eridania Beghin-Say, R&D Centre, Havenstraat.
J Org Chem. 2000 Oct 20;65(21):7000-9. doi: 10.1021/jo0009651.
We have investigated several 1,3-dipolar cycloadditions of a chiral nitrone prepared from L-erythrulose. While cycloadditions to carbon-carbon multiple bonds of dipolarophiles such as ethyl acrylate, ethyl propiolate, or dimethyl acetylenedicarboxylate were poorly stereoselective, reaction with acrylonitrile provided predominantly one diastereomeric adduct. Furthermore, the regioselectivity exhibited by the two structurally similar dipolarophiles ethyl acrylate and ethyl propiolate was found to be opposite. The molecular mechanisms of these cycloadditions have thus been investigated by means of density functional theory (DFT) methods with the B3LYP functional and the 6-31G and 6-31+G basis sets. A simplified achiral version of nitrone 1 as the dipole, and methyl propiolate or acrylonitrile as the dipolarophiles, were chosen as computational models. The cycloadditions have been shown to take place through one-step pathways in which the C-C and C-O sigma bonds are formed in a nonsynchronous way. For the reaction with methyl propiolate, DFT calculations predict the experimentally observed meta regioselectivity. For the reaction with acrylonitrile, however, the predicted regioselectivity has been found to depend on the computational level used. The calculations further indicate the exo approach to be energetically favored in the case of the latter dipolarophile, in agreement with experimental findings. The main reason for this is the steric repulsion between the nitrile function and one of the methyl groups on the nitrone that progressively develops in the alternative endo approach.
我们研究了由L-赤藓糖制备的手性硝酮的几种1,3-偶极环加成反应。虽然与丙烯酸乙酯、丙炔酸乙酯或乙炔二羧酸二甲酯等亲偶极体的碳-碳多重键进行环加成反应时立体选择性较差，但与丙烯腈反应主要生成一种非对映体加合物。此外，发现结构相似的两种亲偶极体丙烯酸乙酯和丙炔酸乙酯表现出相反的区域选择性。因此，利用密度泛函理论（DFT）方法，采用B3LYP泛函以及6-31G和6-31+G基组，对这些环加成反应的分子机制进行了研究。选择硝酮1的简化非手性形式作为偶极体，以及丙炔酸甲酯或丙烯腈作为亲偶极体，作为计算模型。结果表明，环加成反应通过一步途径进行，其中C-C和C-O σ键以非同步方式形成。对于与丙炔酸甲酯的反应，DFT计算预测了实验观察到的间位区域选择性。然而，对于与丙烯腈的反应，发现预测的区域选择性取决于所使用的计算水平。计算进一步表明，在后一种亲偶极体的情况下，外型加成在能量上更有利，这与实验结果一致。主要原因是腈基与硝酮上的一个甲基之间的空间排斥作用，在另一种内型加成途径中这种排斥作用会逐渐增强。
