A mild and practical approach to N-CF3 secondary amines via oxidative fluorination of isocyanides
Abstract N-trifluoromethyl compounds, featuring a CF3 group directly attached to nitrogen, are valuable in medicinal chemistry. Despite substantial advances in their synthesis over the past decade, the efficient preparation of inherently unstable N-CF3 secondary amines remains a challenge in synthet...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60225-2 |
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| author | Jia-Luo Fu Jun-Yunzi Wu Juan-Fen Shi Long-Ling Huang Honggen Wang Qingjiang Li |
| author_facet | Jia-Luo Fu Jun-Yunzi Wu Juan-Fen Shi Long-Ling Huang Honggen Wang Qingjiang Li |
| author_sort | Jia-Luo Fu |
| collection | DOAJ |
| description | Abstract N-trifluoromethyl compounds, featuring a CF3 group directly attached to nitrogen, are valuable in medicinal chemistry. Despite substantial advances in their synthesis over the past decade, the efficient preparation of inherently unstable N-CF3 secondary amines remains a challenge in synthetic chemistry. Herein, we present a mild and practical method for synthesizing these compounds via oxidative fluorination of isocyanides using iodine as the oxidant, silver fluoride as the fluorinating reagent, and tert-butyldimethylsilane as the proton precursor. This approach benefits from simple workup, as all reagents and by-products can be easily removed through simple filtration and evaporation. This protocol features a broad substrate scope, good functional group tolerance, and good to excellent yields. Additionally, the resulting products can be readily converted into N-CF3 carbamoyl fluorides, valuable building blocks for the synthesis of diverse N-CF3 carbonyl derivatives. |
| format | Article |
| id | doaj-art-4006c29c3bd34499897a8e01bb71e449 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-4006c29c3bd34499897a8e01bb71e4492025-08-20T03:16:41ZengNature PortfolioNature Communications2041-17232025-05-0116111010.1038/s41467-025-60225-2A mild and practical approach to N-CF3 secondary amines via oxidative fluorination of isocyanidesJia-Luo Fu0Jun-Yunzi Wu1Juan-Fen Shi2Long-Ling Huang3Honggen Wang4Qingjiang Li5State Key Laboratory of Anti-Infective Drug Discovery and Development, Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen UniversityState Key Laboratory of Anti-Infective Drug Discovery and Development, Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen UniversityState Key Laboratory of Anti-Infective Drug Discovery and Development, Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen UniversityState Key Laboratory of Anti-Infective Drug Discovery and Development, Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen UniversityState Key Laboratory of Anti-Infective Drug Discovery and Development, Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen UniversityState Key Laboratory of Anti-Infective Drug Discovery and Development, Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen UniversityAbstract N-trifluoromethyl compounds, featuring a CF3 group directly attached to nitrogen, are valuable in medicinal chemistry. Despite substantial advances in their synthesis over the past decade, the efficient preparation of inherently unstable N-CF3 secondary amines remains a challenge in synthetic chemistry. Herein, we present a mild and practical method for synthesizing these compounds via oxidative fluorination of isocyanides using iodine as the oxidant, silver fluoride as the fluorinating reagent, and tert-butyldimethylsilane as the proton precursor. This approach benefits from simple workup, as all reagents and by-products can be easily removed through simple filtration and evaporation. This protocol features a broad substrate scope, good functional group tolerance, and good to excellent yields. Additionally, the resulting products can be readily converted into N-CF3 carbamoyl fluorides, valuable building blocks for the synthesis of diverse N-CF3 carbonyl derivatives.https://doi.org/10.1038/s41467-025-60225-2 |
| spellingShingle | Jia-Luo Fu Jun-Yunzi Wu Juan-Fen Shi Long-Ling Huang Honggen Wang Qingjiang Li A mild and practical approach to N-CF3 secondary amines via oxidative fluorination of isocyanides Nature Communications |
| title | A mild and practical approach to N-CF3 secondary amines via oxidative fluorination of isocyanides |
| title_full | A mild and practical approach to N-CF3 secondary amines via oxidative fluorination of isocyanides |
| title_fullStr | A mild and practical approach to N-CF3 secondary amines via oxidative fluorination of isocyanides |
| title_full_unstemmed | A mild and practical approach to N-CF3 secondary amines via oxidative fluorination of isocyanides |
| title_short | A mild and practical approach to N-CF3 secondary amines via oxidative fluorination of isocyanides |
| title_sort | mild and practical approach to n cf3 secondary amines via oxidative fluorination of isocyanides |
| url | https://doi.org/10.1038/s41467-025-60225-2 |
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