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Direct α-alkylation of primary aliphatic amines enabled by CO(2) and electrostatics

Primary aliphatic amines are important building blocks in organic synthesis due to the presence of a synthetically versatile NH(2) group. While N-functionalization of primary amines is well-established, selective C-functionalization of unprotected primary amines remains challenging. Here we report t...

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Autores principales: Ye, Juntao, Kalvet, Indrek, Schoenebeck, Franziska, Rovis, Tomislav
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150826/
https://www.ncbi.nlm.nih.gov/pubmed/30061617
http://dx.doi.org/10.1038/s41557-018-0085-9
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author Ye, Juntao
Kalvet, Indrek
Schoenebeck, Franziska
Rovis, Tomislav
author_facet Ye, Juntao
Kalvet, Indrek
Schoenebeck, Franziska
Rovis, Tomislav
author_sort Ye, Juntao
collection PubMed
description Primary aliphatic amines are important building blocks in organic synthesis due to the presence of a synthetically versatile NH(2) group. While N-functionalization of primary amines is well-established, selective C-functionalization of unprotected primary amines remains challenging. Here we report the use of CO(2) as an activator for the direct transformation of abundant primary aliphatic amines into valuable γ-lactams under photoredox and hydrogen atom transfer (HAT) catalysis. Experimental and computational studies suggest that CO(2) not only inhibits undesired N-alkylation of primary amines but also promotes selective intermolecular HAT by an electrostatically accelerated interaction between the in situ generated negatively charged carbamate and the positively charged quinuclidinium radical. This electrostatic attraction overwhelms the inherent bond dissociation energies which suggest HAT should occur unselectively. We anticipate that our findings will open up new avenues for amine functionalizations as well as selectivity control in HAT reactions.
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spelling pubmed-61508262019-01-30 Direct α-alkylation of primary aliphatic amines enabled by CO(2) and electrostatics Ye, Juntao Kalvet, Indrek Schoenebeck, Franziska Rovis, Tomislav Nat Chem Article Primary aliphatic amines are important building blocks in organic synthesis due to the presence of a synthetically versatile NH(2) group. While N-functionalization of primary amines is well-established, selective C-functionalization of unprotected primary amines remains challenging. Here we report the use of CO(2) as an activator for the direct transformation of abundant primary aliphatic amines into valuable γ-lactams under photoredox and hydrogen atom transfer (HAT) catalysis. Experimental and computational studies suggest that CO(2) not only inhibits undesired N-alkylation of primary amines but also promotes selective intermolecular HAT by an electrostatically accelerated interaction between the in situ generated negatively charged carbamate and the positively charged quinuclidinium radical. This electrostatic attraction overwhelms the inherent bond dissociation energies which suggest HAT should occur unselectively. We anticipate that our findings will open up new avenues for amine functionalizations as well as selectivity control in HAT reactions. 2018-07-30 2018-10 /pmc/articles/PMC6150826/ /pubmed/30061617 http://dx.doi.org/10.1038/s41557-018-0085-9 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms Reprints and permissions information is available at www.nature.com/reprints.
spellingShingle Article
Ye, Juntao
Kalvet, Indrek
Schoenebeck, Franziska
Rovis, Tomislav
Direct α-alkylation of primary aliphatic amines enabled by CO(2) and electrostatics
title Direct α-alkylation of primary aliphatic amines enabled by CO(2) and electrostatics
title_full Direct α-alkylation of primary aliphatic amines enabled by CO(2) and electrostatics
title_fullStr Direct α-alkylation of primary aliphatic amines enabled by CO(2) and electrostatics
title_full_unstemmed Direct α-alkylation of primary aliphatic amines enabled by CO(2) and electrostatics
title_short Direct α-alkylation of primary aliphatic amines enabled by CO(2) and electrostatics
title_sort direct α-alkylation of primary aliphatic amines enabled by co(2) and electrostatics
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150826/
https://www.ncbi.nlm.nih.gov/pubmed/30061617
http://dx.doi.org/10.1038/s41557-018-0085-9
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