Deoxygenative photochemical alkylation of secondary amides enables a streamlined synthesis of substituted amines
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....
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56234-w |
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| author | Antonio Pulcinella Stefano Bonciolini Robin Stuhr Damiano Diprima Minh Thao Tran Magnus Johansson Axel Jacobi von Wangelin Timothy Noël |
| author_facet | Antonio Pulcinella Stefano Bonciolini Robin Stuhr Damiano Diprima Minh Thao Tran Magnus Johansson Axel Jacobi von Wangelin Timothy Noël |
| author_sort | Antonio Pulcinella |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-edfea1d15e6446d1ac7b0503f2176fc7 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-edfea1d15e6446d1ac7b0503f2176fc72025-01-26T12:42:42ZengNature PortfolioNature Communications2041-17232025-01-0116111010.1038/s41467-025-56234-wDeoxygenative photochemical alkylation of secondary amides enables a streamlined synthesis of substituted aminesAntonio Pulcinella0Stefano Bonciolini1Robin Stuhr2Damiano Diprima3Minh Thao Tran4Magnus Johansson5Axel Jacobi von Wangelin6Timothy Noël7Flow Chemistry Group, Van’t Hoff Institute for Molecular Sciences (HIMS), University of AmsterdamFlow Chemistry Group, Van’t Hoff Institute for Molecular Sciences (HIMS), University of AmsterdamFlow Chemistry Group, Van’t Hoff Institute for Molecular Sciences (HIMS), University of AmsterdamFlow Chemistry Group, Van’t Hoff Institute for Molecular Sciences (HIMS), University of AmsterdamJanssen Pharmaceutica NVMedicinal Chemistry, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZenecaDepartment of Chemistry, University of HamburgFlow Chemistry Group, Van’t Hoff Institute for Molecular Sciences (HIMS), University of AmsterdamAbstract 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.https://doi.org/10.1038/s41467-025-56234-w |
| spellingShingle | Antonio Pulcinella Stefano Bonciolini Robin Stuhr Damiano Diprima Minh Thao Tran Magnus Johansson Axel Jacobi von Wangelin Timothy Noël Deoxygenative photochemical alkylation of secondary amides enables a streamlined synthesis of substituted amines Nature Communications |
| title | Deoxygenative photochemical alkylation of secondary amides enables a streamlined synthesis of substituted amines |
| title_full | Deoxygenative photochemical alkylation of secondary amides enables a streamlined synthesis of substituted amines |
| title_fullStr | Deoxygenative photochemical alkylation of secondary amides enables a streamlined synthesis of substituted amines |
| title_full_unstemmed | Deoxygenative photochemical alkylation of secondary amides enables a streamlined synthesis of substituted amines |
| title_short | Deoxygenative photochemical alkylation of secondary amides enables a streamlined synthesis of substituted amines |
| title_sort | deoxygenative photochemical alkylation of secondary amides enables a streamlined synthesis of substituted amines |
| url | https://doi.org/10.1038/s41467-025-56234-w |
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