Deoxygenative photochemical alkylation of secondary amides enables a streamlined synthesis of substituted amines

Secondary amines are vital functional groups in pharmaceuticals, agrochemicals, and natural products, necessitating efficient synthetic methods. Traditional approaches, including N-monoalkylation and reductive amination, suffer from limitations such as poor chemoselectivity and complexity. Herein, we present a streamlined deoxygenative photochemical alkylation of secondary amides, enabling the efficient synthesis of α-branched secondary amines. Our method leverages triflic anhydride-mediated semi-reduction of amides to imines, followed by a photochemical radical alkylation step. This approach broadens the synthetic utility of amides, facilitating late-stage modifications of drug-like molecules and the synthesis of saturated N-substituted heterocycles. The pivotal role of flow technology in developing a scalable and robust process underscores the practicality of this method, significantly expanding the organic chemist's toolbox for complex amine synthesis.

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Publication Details

Journal
Nature Communications
Published
2025-01-22
DOI
https://doi.org/10.1038/s41467-025-56234-w
Citations
14
Primary Topic
Advanced Synthetic Organic Chemistry
Type
article
Field-Weighted Citation Impact
13.10

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article

Deoxygenative photochemical alkylation of secondary amides enables a streamlined synthesis of substituted amines

Robin Stuhr, Magnus J. Johansson, Axel Jacobi von Wangelin, Stefano Bonciolini et al.
14 citations
Nature Communications
Advanced Synthetic Organic Chemistry
13.10
article

Deoxygenative photochemical alkylation of secondary amides enables a streamlined synthesis of substituted amines

Robin Stuhr, Magnus J. Johansson, Axel Jacobi von Wangelin, Stefano Bonciolini, Timothy Noël, Antonio Pulcinella, Damiano Diprima, Minh Tran
article en
14 citations

Abstract

Secondary amines are vital functional groups in pharmaceuticals, agrochemicals, and natural products, necessitating efficient synthetic methods. Traditional approaches, including N-monoalkylation and reductive amination, suffer from limitations such as poor chemoselectivity and complexity. Herein, we present a streamlined deoxygenative photochemical alkylation of secondary amides, enabling the efficient synthesis of α-branched secondary amines. Our method leverages triflic anhydride-mediated semi-reduction of amides to imines, followed by a photochemical radical alkylation step. This approach broadens the synthetic utility of amides, facilitating late-stage modifications of drug-like molecules and the synthesis of saturated N-substituted heterocycles. The pivotal role of flow technology in developing a scalable and robust process underscores the practicality of this method, significantly expanding the organic chemist's toolbox for complex amine synthesis.

Nature CommunicationsVol. 16(1)
Janssen (Belgium) (BE), Universität Hamburg (DE), AstraZeneca (Sweden) (SE), University of Amsterdam (NL)
European Commission, Horizon 2020 Framework Programme
Openalex Percentile: Top 1%
Advanced Synthetic Organic Chemistry
13.10
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Deoxygenative photochemical alkylation of secondary amides enables a streamlined synthesis of substituted amines — Robin Stuhr, Magnus J. Johansson, et al. · Nature Communications (2025) | TGRS Research Map | TGRS