Stereochemistry as a tool in deciphering the processes of a tandem iminium cyclization and Smiles rearrangement.
Stereochemistry as a tool in deciphering the processes of a tandem iminium cyclization and Smiles rearrangement.
复制标题
DOI：
10.1021/jo101798p
复制
发表时间：
2010-11
期刊：
影响因子：
--
通讯作者：
Jinbao Xiang;T. Zhu;Q. Dang;X. Bai
中科院分区：
文献类型：
--
作者：
Jinbao Xiang;T. Zhu;Q. Dang;X. Bai
为了了解最近报道的串联亚胺环化和Smiles重排的详细机理，通过监测其立体化学过程来研究手性底物的反应过程。在串联反应条件下，衍生自l-脯氨醇的手性醛1导致两个令人惊讶的结果。首先，亚胺鎓环化得到非对映异构体混合物，其中顺式构型的产物为主要产物。其次，顺式和反式2的Smiles重排导致直接衍生自反式异构体的相同产物3a。前者是合理化的假设的克拉姆的螯合物过渡态，导致顺式产品的动力学青睐。后者是由于反式/顺式对之间的平衡，包括碳正离子中间体和空间位阻，这阻止了顺式异构体进行分子内亲核取代。竞争实验的结果进一步支持了这一假设，其中在重排步骤中加入1当量的对甲氧基苯胺导致大量的苯胺基交换的重排产物。
To understand the detailed mechanism of a recently reported tandem iminium cyclization and Smiles rearrangement, the reaction processes of a chiral substrate were investigated by monitoring its stereochemical courses. Under the tandem reaction conditions, chiral aldehyde 1 derived from l-prolinol led to two surprising results. First, the iminium cyclization gave a diastereomeric mixture with the cis-configured product as the predominant one. Second, Smiles rearrangement of both cis- and trans-2 led to the same product 3a directly derived from the trans isomer. The former was rationalized by the postulation of a Cram's chelate transition state leading to the cis product as kinetically favored. The latter was due to the equilibration between the trans/cis pair involving a carbocation intermediate and the steric hindrance, which prevented the cis isomer from undergoing the intramolecular nucleophilic substitution. This hypothesis was further supported by the results of a competition experiment in which the addition of 1 equiv of p-methoxyaniline in the rearrangement step led to a significant amount of anilinyl-exchanged rearrangement product.