A mild and practical approach to N-CF3 secondary amines via oxidative fluorination of isocyanides

Jia-Luo Fu, Jun-Yunzi Wu, Juan-Fen Shi, Long-Ling Huang, Honggen Wang () and Qingjiang Li ()
Additional contact information
Jia-Luo Fu: Sun Yat-sen University
Jun-Yunzi Wu: Sun Yat-sen University
Juan-Fen Shi: Sun Yat-sen University
Long-Ling Huang: Sun Yat-sen University
Honggen Wang: Sun Yat-sen University
Qingjiang Li: Sun Yat-sen University

Nature Communications, 2025, vol. 16, issue 1, 1-10

Abstract: 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.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-60225-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60225-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-60225-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().