Aggarwal Varinder K, Harvey Jeremy N, Richardson Jeffery
School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, U.K.
J Am Chem Soc. 2002 May 22;124(20):5747-56. doi: 10.1021/ja025633n.
Sulfur ylides R(2)S(+)-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(+)Me(2))-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.
硫叶立德R(2)S(+)-C(-)HR' 与醛R''-CHO反应生成环氧化物，主要生成反式异构体，这是一种在合成中有用的反应，其不对称变体中使用手性硫化物的情况越来越多。使用密度泛函理论、B3LYP密度泛函和灵活基组详细研究了“模型”反应（R = Me，R' = R'' = H）和生成氧化芪的反应（R = Me，R' = R'' = Ph）。结果表明，对于这个涉及高极性中间体的反应，需要始终使用连续溶剂化模型才能获得合理的结果。对于苯甲醛与苄基二甲基锍叶立德的反应，关键步骤显示为叶立德与醛的准[2 + 2]加成，形成内盐R'-CH(S(+)Me(2))-CH(O(-))-R''，其中带电基团彼此呈邻位交叉，以及围绕内盐的C-C单键进行扭转旋转，以形成两个带电基团呈反式的旋转异构体。发现从内盐的第二个旋转异构体中消除硫化物这一最后步骤很容易。在导致反式氧化芪的反式途径中，发现初始加成是速率决定步骤，而对于导致顺式环氧化物的非对映体顺式途径，最慢的是扭转旋转。与之前的计算工作不同，这些结果与实验结果非常吻合。扭转旋转步骤出人意料且显然前所未有的（对于形成C-C键的反应而言）重要性，特别是在顺式情况下，是由于所有涉及的势垒都较低。这种新颖的机理图景为用于对映选择性环氧化物合成的手性硫化物的未来发展提供了坚实的基础。
