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A general, versatile and divergent synthesis of selectively deuterated amines

Deuterated organic molecules are of utmost importance in many areas of science and have been recently intensively investigated in medicinal chemistry due to their enhanced metabolic stability. The development of efficient and broadly applicable methods for the selective incorporation of deuterium at...

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Autores principales: Lecomte, Morgan, Lahboubi, Mounsef, Thilmany, Pierre, El Bouzakhi, Adil, Evano, Gwilherm
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386668/
https://www.ncbi.nlm.nih.gov/pubmed/34522313
http://dx.doi.org/10.1039/d1sc02622d
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author Lecomte, Morgan
Lahboubi, Mounsef
Thilmany, Pierre
El Bouzakhi, Adil
Evano, Gwilherm
author_facet Lecomte, Morgan
Lahboubi, Mounsef
Thilmany, Pierre
El Bouzakhi, Adil
Evano, Gwilherm
author_sort Lecomte, Morgan
collection PubMed
description Deuterated organic molecules are of utmost importance in many areas of science and have been recently intensively investigated in medicinal chemistry due to their enhanced metabolic stability. The development of efficient and broadly applicable methods for the selective incorporation of deuterium atoms into organic molecules from readily available starting materials and reagents is therefore of extreme importance. Such methods however often lack generality and selectivity, notably in the nitrogen series. With nitrogen-containing molecules being indeed ubiquitous in medicinal chemistry, there is a strong need for efficient methods enabling the selective synthesis of deuterated amines. In this perspective, we report herein a general, versatile, divergent and metal-free synthesis of amines selectively deuterated at their α and/or β positions. Upon simple treatment of readily available ynamides with a mixture of triflic acid and triethylsilane, either deuterated or not, a range of amines can be smoothly obtained with high levels of deuterium incorporation by a unique sequence involving a domino keteniminium/iminium activation.
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spelling pubmed-83866682021-09-13 A general, versatile and divergent synthesis of selectively deuterated amines Lecomte, Morgan Lahboubi, Mounsef Thilmany, Pierre El Bouzakhi, Adil Evano, Gwilherm Chem Sci Chemistry Deuterated organic molecules are of utmost importance in many areas of science and have been recently intensively investigated in medicinal chemistry due to their enhanced metabolic stability. The development of efficient and broadly applicable methods for the selective incorporation of deuterium atoms into organic molecules from readily available starting materials and reagents is therefore of extreme importance. Such methods however often lack generality and selectivity, notably in the nitrogen series. With nitrogen-containing molecules being indeed ubiquitous in medicinal chemistry, there is a strong need for efficient methods enabling the selective synthesis of deuterated amines. In this perspective, we report herein a general, versatile, divergent and metal-free synthesis of amines selectively deuterated at their α and/or β positions. Upon simple treatment of readily available ynamides with a mixture of triflic acid and triethylsilane, either deuterated or not, a range of amines can be smoothly obtained with high levels of deuterium incorporation by a unique sequence involving a domino keteniminium/iminium activation. The Royal Society of Chemistry 2021-07-13 /pmc/articles/PMC8386668/ /pubmed/34522313 http://dx.doi.org/10.1039/d1sc02622d Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Lecomte, Morgan
Lahboubi, Mounsef
Thilmany, Pierre
El Bouzakhi, Adil
Evano, Gwilherm
A general, versatile and divergent synthesis of selectively deuterated amines
title A general, versatile and divergent synthesis of selectively deuterated amines
title_full A general, versatile and divergent synthesis of selectively deuterated amines
title_fullStr A general, versatile and divergent synthesis of selectively deuterated amines
title_full_unstemmed A general, versatile and divergent synthesis of selectively deuterated amines
title_short A general, versatile and divergent synthesis of selectively deuterated amines
title_sort general, versatile and divergent synthesis of selectively deuterated amines
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386668/
https://www.ncbi.nlm.nih.gov/pubmed/34522313
http://dx.doi.org/10.1039/d1sc02622d
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