Unraveling the mechanism of epoxide formation from sulfur ylides and aldehydes
Unraveling the mechanism of epoxide formation from sulfur ylides and aldehydes
复制标题
DOI：
10.1021/ja025633n
复制
发表时间：
2002-05-22
影响因子：
15
通讯作者：
Richardson, J
中科院分区：
文献类型：
--
作者：
Aggarwal, VK;Harvey, JN;Richardson, J
硫叶立德R2 S +-C-HR'与醛R”-CHO反应形成环氧化物，主要作为反式异构体，在合成有用的反应中，其越来越多地以其不对称变体与手性硫化物一起使用。采用密度泛函理论、B3 LYP密度泛函和柔性基组方法对模型反应（R = Me，R '= R”= H）和生成氧化二苯乙烯（R = Me，R' = R”= Ph）的反应机理进行了详细的研究.结果表明，对于这种涉及高极性中间体的反应，需要自始至终使用连续溶剂化模型以获得合理的结果。苯甲醛与二甲基锍苄叉反应的关键步骤是苄叉与醛的准[2 + 2]加成，形成带电荷基团相互交错的甜菜碱R '-CH（S+ Me 2）-CH（O-）-R”，并围绕甜菜碱的C-C单键发生扭转旋转，形成带有两个带电荷基团anti的旋转异构体.发现最后一步，从甜菜碱的第二旋转异构体中消除硫化物是容易的。在反途径的情况下，导致反式-二苯乙烯环氧化物，初始添加被发现是速率决定，而对于非对映体的顺式途径，导致顺式-环氧化物，它反而是扭转旋转是最慢的。这些结果与实验非常吻合，不同于以前的计算工作。扭转旋转步骤，特别是在顺式情况下，出乎意料的和显然前所未有的（对于C-C键形成反应）重要性是由于所有涉及的势垒都是低的。这一新的反应机理为手性硫醚在不对称环氧化物合成中的应用奠定了基础。
Sulfur ylides R2S+-C-HR' react with aldehydes R"-CHO to form epoxides, predominantly as the trans isomers, in a synthetically useful reaction which is increasingly used in its asymmetric variant with chiral sulfides. The mechanisms of the "model" reaction (R = Me, R' = R" = H) and the reaction forming stilbene oxide (R = Me, R' = R" = Ph) have been studied in detail using density functional theory, the B3LYP density functional, and flexible basis sets. It has been shown that for this reaction involving highly polar intermediates, continuum solvation models need to be used throughout to obtain reasonable results. For the reaction of benzaldehyde with dimethylsulfonium benzylide, the key steps are shown to be quasi [2 + 2] addition of the ylide to the aldehyde to form a betaine R'-CH(S+Me2)-CH(O-)-R" in which the charged groups are gauche to one another, and torsional rotation around the C-C single bond of the betaine to form its rotamer with the two charged groups anti. The final step, elimination of sulfide from this second rotamer of the betaine, is found to be facile. In the case of the anti pathway, leading to trans-stilbene epoxide, the initial addition is found to be rate-determining, whereas for the diastereomeric syn pathway, leading to the cis-epoxide, it is instead the torsional rotation which is slowest. These results are in excellent agreement with experiment, unlike previous computational work. The unexpected and apparently unprecedented (for C-C bond-forming reactions) importance of the torsional rotation step, especially in the syn case, is due to the fact that all the barriers involved are low-lying. This novel picture of the mechanism provides a sound basis for the future development of chiral sulfides for enantioselective epoxide synthesis.