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.
Authors
- Robin Stuhr (ORCID: https://orcid.org/0000-0001-5932-1747)
- Magnus J. Johansson (ORCID: https://orcid.org/0000-0002-0904-2835)
- Axel Jacobi von Wangelin (ORCID: https://orcid.org/0000-0001-7462-0745)
- Stefano Bonciolini (ORCID: https://orcid.org/0000-0002-2239-2549)
- Timothy Noël (ORCID: https://orcid.org/0000-0002-3107-6927)
- Antonio Pulcinella (ORCID: https://orcid.org/0000-0001-7934-4225)
- Damiano Diprima (ORCID: https://orcid.org/0009-0009-0200-1449)
- Minh Tran
Institutions
- Janssen (Belgium) (BE)
- Universität Hamburg (DE)
- AstraZeneca (Sweden) (SE)
- University of Amsterdam (NL)
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
Funders
- European Commission
- Horizon 2020 Framework Programme