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...

Full description

Bibliographic Details
Main Authors:	Andrews, Keith G., Faizova, Radmilla, Denton, Ross M.
Format:	Article
Language:	English
Published:	Nature Publishing Group 2017
Online Access:	http://eprints.nottingham.ac.uk/43664/ http://eprints.nottingham.ac.uk/43664/ http://eprints.nottingham.ac.uk/43664/ http://eprints.nottingham.ac.uk/43664/1/RDenton2%20A%20Practical%20and%20catalyst%20free%20%282%29.pdf

id	nottingham-43664
recordtype	eprints
spelling	nottingham-436642017-11-24T12:51:51Z http://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 application/pdf en cc_by http://eprints.nottingham.ac.uk/43664/1/RDenton2%20A%20Practical%20and%20catalyst%20free%20%282%29.pdf Andrews, Keith G. and 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
repository_type	Digital Repository
institution_category	Local University
institution	University of Nottingham Malaysia Campus
building	Nottingham Research Data Repository
collection	Online Access
language	English
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.
format	Article
author	Andrews, Keith G. Faizova, Radmilla Denton, Ross M.
spellingShingle	Andrews, Keith G. Faizova, Radmilla Denton, Ross M. A practical and catalyst-free trifluoroethylation reaction of amines using trifluoroacetic acid
author_facet	Andrews, Keith G. Faizova, Radmilla Denton, Ross M.
author_sort	Andrews, Keith G.
title	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_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_sort	practical and catalyst-free trifluoroethylation reaction of amines using trifluoroacetic acid
publisher	Nature Publishing Group
publishDate	2017
url	http://eprints.nottingham.ac.uk/43664/ http://eprints.nottingham.ac.uk/43664/ http://eprints.nottingham.ac.uk/43664/ http://eprints.nottingham.ac.uk/43664/1/RDenton2%20A%20Practical%20and%20catalyst%20free%20%282%29.pdf
first_indexed	2018-09-06T13:27:57Z
last_indexed	2018-09-06T13:27:57Z
_version_	1610864894543921152

A practical and catalyst-free trifluoroethylation reaction of amines using trifluoroacetic acid

Similar Items