Flores-Bernal Gustavo G, Vargas-Díaz Ma Elena, Jiménez-Vázquez Hugo A, Hernández-Rodríguez Marcos, Zepeda-Vallejo L Gerardo
Department of Organic Chemistry, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prol. de Carpio y Plan de Ayala s/n, 11340 Mexico City, Mexico.
Department of Organic Chemistry, Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, 04510 Mexico City, Mexico.
ACS Omega. 2023 May 3;8(23):20611-20620. doi: 10.1021/acsomega.3c01161. eCollection 2023 Jun 13.
Pseudo--symmetric dodecaheterocyclic structures, which possess two acyl/aroyl groups disposed on either a cis- or trans-relative configuration, were prepared from the naturally occurring (-)-(1)-myrtenal. Addition of Grignard reagents (RMgX) to the diastereoisomeric mixture of these compounds unexpectedly showed that nucleophilic additions to the two prochiral carbonyl centers gave the same stereochemical result in both cis/trans diastereoisomers, making unnecessary the separation of this mixture. Noticeably, both carbonyl groups showed different reactivity because one of them is attached to an acetalic carbon and the other to a thioacetalic carbon. Furthermore, addition of RMgX to the carbonyl attached to the former carbon takes place through the face, while addition to the second one proceeds through the face, thus affording the corresponding carbinols in a highly diastereoselective process. This structural feature allowed the sequential hydrolysis of both carbinols, yielding separately ()- and ()-1,2-diols after reduction with NaBH. The mechanism of the asymmetric Grignard addition was explained by density functional theory calculations. This approach contributes to the development of the divergent synthesis of structurally and/or configurationally different chiral molecules.
由天然存在的(-)-(1)-桃金娘烯醛制备了具有两个以顺式或反式相对构型排列的酰基/芳酰基的伪对称十二元杂环结构。将格氏试剂(RMgX)添加到这些化合物的非对映异构体混合物中，意外地发现，对两个前手性羰基中心的亲核加成在顺式/反式非对映异构体中都给出了相同的立体化学结果，因此无需分离该混合物。值得注意的是，两个羰基表现出不同的反应性，因为其中一个连接到缩醛碳上，另一个连接到硫代缩醛碳上。此外，RMgX添加到连接到前一种碳的羰基上是通过面进行的，而添加到第二个羰基上是通过面进行的，从而在高度非对映选择性过程中得到相应的甲醇。这一结构特征允许对两种甲醇进行顺序水解，在用NaBH还原后分别得到()-和()-1,2-二醇。通过密度泛函理论计算解释了不对称格氏加成的机理。这种方法有助于开发结构和/或构型不同的手性分子的发散合成。
