A practical and catalyst-free trifluoroethylation reaction of amines using trifluoroacetic acid
| Autor: | Ross M. Denton, Radmilla Faizova, Keith G. Andrews |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Multidisciplinary
Primary (chemistry) Silylation 010405 organic chemistry Science General Physics and Astronomy chemistry.chemical_element General Chemistry 010402 general chemistry 01 natural sciences Article General Biochemistry Genetics and Molecular Biology 0104 chemical sciences Catalysis chemistry.chemical_compound chemistry Reagent Functional group Fluorine Trifluoroacetic acid Organic chemistry Selectivity |
| Zdroj: | Nature Communications, Vol 8, Iss 1, Pp 1-6 (2017) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Amines are a fundamentally important class of biologically active compounds and the ability to manipulate their physicochemical properties through the introduction of fluorine is of paramount importance in medicinal chemistry. Current synthesis methods for the construction of fluorinated amines rely on air and moisture sensitive reagents that require special handling or harsh reductants that limit functionality. Here we report practical, catalyst-free, reductive trifluoroethylation reactions of free amines exhibiting remarkable functional group tolerance. The reactions proceed in conventional glassware without rigorous exclusion of either moisture or oxygen, and use trifluoroacetic acid as a stable and inexpensive fluorine source. The new methods provide access to a wide range of medicinally relevant functionalized tertiary β-fluoroalkylamine cores, either through direct trifluoroethylation of secondary amines or via a three-component coupling of primary amines, aldehydes and trifluoroacetic acid. A reduction of in situ-generated silyl ester species is proposed to account for the reductive selectivity observed. Amino and trifluoromethyl groups are ubiquitous within medicinal chemistry, but synthesis of fluoroalkylamines normally requires harsh conditions or sensitive reagents. Here the authors report an operationally simple, catalyst-free procedure for the trifluoroethylation of primary and secondary amines. |
| Databáze: | OpenAIRE |
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