| Autor: |
Novaes, Luiz F. T., Ho, Justin S. K., Mao, Kaining, Villemure, Elisia, Terrett, Jack A., Lin, Song |
| Zdroj: |
Journal of the American Chemical Society; August 2024, Vol. 146 Issue: 33 p22982-22992, 11p |
| Abstrakt: |
Incorporation of C(sp3)–F bonds in biologically active compounds is a common strategy employed in medicinal and agricultural chemistry to tune pharmacokinetic and pharmacodynamic properties. Due to the limited number of robust strategies for C(sp3)–H fluorination of complex molecules, time-consuming de novosyntheses of such fluorinated analogs are typically required, representing a major bottleneck in the drug discovery process. In this work, we present a general and operationally simple strategy for site-specific β-C(sp3)–H fluorination of amine derivatives including carbamates, amides, and sulfonamides, which is compatible with a wide range of functional groups including N-heteroarenes. In this approach, an improved electrochemical Shono oxidation is used to set the site of functionalization via net α,β-desaturation to access enamine derivatives. We further developed a series of new transformations of these enamine intermediates to synthesize a variety of β-fluoro-α-functionalized structures, allowing efficient access to pertinent targets to accelerate drug discovery campaigns. |
| Databáze: |
Supplemental Index |
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