Asymmetric Aza-Wacker-Type Cyclization of N-Ts Hydrazine-Tethered Tetrasubstituted Olefins: Synthesis of Pyrazolines Bearing One Quaternary or Two Vicinal Stereocenters
| Autor: | Qihang Shao, Xuezhen Kou, Guoqiang Yang, Wanbin Zhang, Chenghao Ye |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
chemistry.chemical_classification
Olefin fiber Double bond 010405 organic chemistry Hydrazine Substituent General Chemistry 010402 general chemistry 01 natural sciences Biochemistry Medicinal chemistry Catalysis 0104 chemical sciences Stereocenter chemistry.chemical_compound Colloid and Surface Chemistry chemistry Vicinal Alkyl Methyl group |
| Zdroj: | Journal of the American Chemical Society. 140(24) |
| ISSN: | 1520-5126 |
| Popis: | We have developed an asymmetric aza-Wacker-type cyclization of N-Ts hydrazine-tethered tetrasubstituted olefins, affording optically active pyrazolines bearing chiral tetrasubstituted carbon stereocenters. This reaction is tolerant to a broad range of substrates under mild reaction conditions, giving the desired chiral products with high enantioselectivities. Generation of two vicinal stereocenters on the C═C double bonds was also achieved with high selectivities, a process which has been rarely studied for Wacker-type reactions. A mechanistic study revealed that this aza-Wacker-type cyclization undergoes a syn-aminopalladation process. It was also found that for substrates bearing two linear alkyl substituents on the outer carbon atom of the olefin, both of which are larger than a methyl group, the alkyl substituent that is cis to the intranucleophilic group participates more readily in β-hydride elimination. When one of the two alkyl substituents on the outer carbon atom of the olefin is a methyl group, β-hydride elimination proceeds selectively at the methylene side, thus both diastereomers can be prepared via switching the configuration of the olefin. Furthermore, the product can be converted to a pharmaceutical compound in high yields over three steps. |
| Databáze: | OpenAIRE |
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