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Asymmetric construction of allylicstereogenic carbon center featuring atrifluoromethyl group via enantioselective reductive fluoroalkylation

Emerging as a powerful tool for lead optimization in pharmaceutical research and development, to develop the facile, general protocols that allows the incorporation of fluorine-containing motif in drug candidates has accumulated enormous research interest in recent years. Among these important motif...

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Detalles Bibliográficos
Autores principales: Jin, Ruo-Xing, Wu, Bing-Bing, Bian, Kang-Jie, Yu, Jian-Liang, Dai, Jing-Cheng, Zuo, Ya-Wen, Zhang, Yi-Fan, Wang, Xi-Sheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9672039/
https://www.ncbi.nlm.nih.gov/pubmed/36396652
http://dx.doi.org/10.1038/s41467-022-34841-1
Descripción
Sumario:Emerging as a powerful tool for lead optimization in pharmaceutical research and development, to develop the facile, general protocols that allows the incorporation of fluorine-containing motif in drug candidates has accumulated enormous research interest in recent years. Among these important motifs, the incorporation of strategic motif CF(3) on aliphatic chain especially with the concomitant construction of trifluoromethylated alkanes bearing a CF(3)-substituted stereogenic carbon, is of paramount importance. Herein, we disclose an asymmetric nickel-catalyzed reductive trifluoroalkylation of alkenyl halides for enantioselective syntheses of diverse α-trifluoromethylated allylic alkanes, offering a general protocol to access the trifluoromethyl analogue to chiral α-methylated allylic alkanes, one of the most prevalent key components among natural products and pharmaceuticals. Utilities of the method including the application of the asymmetric trifluoroalkylation on multiple biologically active complex molecules, derivatization of transformable alkenyl functionality were demonstrated, providing a facile method in the diversity-oriented syntheses of CF(3)-containing chiral drugs and bioactive-molecules.