A practical and catalyst-free trifluoroethylation reaction of amines using trifluoroacetic acid
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...
| Main Authors: | , , |
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| Format: | Article |
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Nature Publishing Group
2017
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| Online Access: | https://eprints.nottingham.ac.uk/43664/ |
| _version_ | 1848796739233906688 |
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| author | Andrews, Keith G. Faizova, Radmilla Denton, Ross M. |
| author_facet | Andrews, Keith G. Faizova, Radmilla Denton, Ross M. |
| author_sort | Andrews, Keith G. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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 beta-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. |
| first_indexed | 2025-11-14T19:52:46Z |
| format | Article |
| id | nottingham-43664 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:52:46Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-436642020-05-04T18:51:47Z https://eprints.nottingham.ac.uk/43664/ A practical and catalyst-free trifluoroethylation reaction of amines using trifluoroacetic acid Andrews, Keith G. Faizova, Radmilla Denton, Ross M. 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 beta-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. Nature Publishing Group 2017-06-26 Article PeerReviewed Andrews, Keith G., Faizova, Radmilla and Denton, Ross M. (2017) A practical and catalyst-free trifluoroethylation reaction of amines using trifluoroacetic acid. Nature Communications, 8 . 15913/1-15913/6. ISSN 2041-1723 https://www.nature.com/articles/ncomms15913 doi:10.1038/ncomms15913 doi:10.1038/ncomms15913 |
| spellingShingle | Andrews, Keith G. Faizova, Radmilla Denton, Ross M. A practical and catalyst-free trifluoroethylation reaction of amines using trifluoroacetic acid |
| title | A practical and catalyst-free trifluoroethylation reaction of amines using trifluoroacetic acid |
| title_full | A practical and catalyst-free trifluoroethylation reaction of amines using trifluoroacetic acid |
| title_fullStr | A practical and catalyst-free trifluoroethylation reaction of amines using trifluoroacetic acid |
| title_full_unstemmed | A practical and catalyst-free trifluoroethylation reaction of amines using trifluoroacetic acid |
| title_short | A practical and catalyst-free trifluoroethylation reaction of amines using trifluoroacetic acid |
| title_sort | practical and catalyst-free trifluoroethylation reaction of amines using trifluoroacetic acid |
| url | https://eprints.nottingham.ac.uk/43664/ https://eprints.nottingham.ac.uk/43664/ https://eprints.nottingham.ac.uk/43664/ |