Diversity‐Oriented Synthesis of Aliphatic Fluorides via Reductive C(sp3)−C(sp3) Cross‐Coupling Fluoroalkylation
| Autor: | Shan-Xiu Ni, Guang-Xu Liao, Bing-Bing Wu, Ru Cui, Kang-Jie Bian, Jie Sheng, Xi-Sheng Wang, Yan He, Hui-Qi Ni |
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| Rok vydání: | 2021 |
| Předmět: |
chemistry.chemical_classification
010405 organic chemistry Chemistry Bromofluoromethane Alkyl bromide chemistry.chemical_element Halide General Medicine General Chemistry 010402 general chemistry 01 natural sciences Combinatorial chemistry Catalysis 0104 chemical sciences chemistry.chemical_compound Nickel Alkyl |
| Zdroj: | Angewandte Chemie International Edition. 60:15020-15027 |
| ISSN: | 1521-3773 1433-7851 |
| Popis: | Monofluorinated alkyl compounds are of great importance in pharmaceuticals, agrochemicals and materials. Herein, we describe a direct nickel-catalyzed monofluoromethylation of unactivated alkyl halides using a low-cost industrial raw material, bromofluoromethane, by demonstrating a general and efficient reductive cross-coupling of two alkyl halides. Results with 1-bromo-1-fluoroalkane also demonstrate the viability of monofluoroalkylation, which further established the first example of reductive C(sp3 )-C(sp3 ) cross-coupling fluoroalkylation. These transformations demonstrate high efficiency, mild conditions, and excellent functional-group compatibility, especially for a range of pharmaceuticals and biologically active compounds. Mechanistic studies support a radical pathway. Kinetic studies reveal that the reaction is first-order dependent on catalyst and alkyl bromide whereas the generation of monofluoroalkyl radical is not involved in the rate-determining step. This strategy provides a general and efficient method for the synthesis of aliphatic fluorides. |
| Databáze: | OpenAIRE |
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