Stereochemistry as a tool in deciphering the processes of a tandem iminium cyclization and Smiles rearrangement.
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.
The Center for Combinatorial Chemistry and Drug Discovery, The School of Pharmaceutical Sciences and The College of Chemistry, Jilin University, 1266 Fujin Road, Changchun, Jilin 130021, P. R. China.
Jinbao
J
Xiang
Tong
T
Zhu
Qun
Q
Dang
Xu
X
Bai
D000814:Aniline Compounds / Q000737:chemistry*; D002384:Catalysis; D002412:Cations / Q000737:chemistry*; D003500:Cyclization; D007097:Imines / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
D000814:Aniline Compounds; D002412:Cations; D007097:Imines