Synthesis and <i>meta</i> -Amination of Pyridines via Multicomponent Cascade Reaction
We report a green, multicomponent cascade synthesis of 3-aminopyridines <i>via</i> [1,3'-bipyridin]-1-ium intermediates undergoing Zincke aminolysis with ammonia supported by experimental evidence and DFT calculations. The method offers broad scope (>20 examples), good functional group tolerance, and scalability in batch and flow procedures. Synthetic utility is demonstrated through conversion into 3-halo, 3-hydroxy, and 3-thiopyridines, expanding the access to <i>meta</i>-substituted pyridines through peripheral editing of the unprotected amino group.
Authors
- Telmo N. Francisco (ORCID: https://orcid.org/0000-0002-7511-4374)
- Carlos A. M. Afonso (ORCID: https://orcid.org/0000-0002-7284-5948)
- Rafael F. A. Gomes (ORCID: https://orcid.org/0000-0002-2598-8540)
- Hélio M. T. Albuquerque (ORCID: https://orcid.org/0000-0001-5905-3316)
- Samuel Guieu (ORCID: https://orcid.org/0000-0002-7439-209X)
- Joana L. C. Sousa (ORCID: https://orcid.org/0000-0003-1412-4197)
- Nuno R. Candeias (ORCID: https://orcid.org/0000-0003-2414-9064)
- Artur M. S. Silva (ORCID: https://orcid.org/0000-0003-2861-8286)
Institutions
- University of Lisbon (PT)
- Tampere University (FI)
- Institute for Medical Research (AR)
- Rede de Química e Tecnologia (PT)
- University of Aveiro (PT)
Publication Details
- Journal
- Organic Letters
- Published
- 2025-10-13
- DOI
- https://doi.org/10.1021/acs.orglett.5c03509
- Primary Topic
- Catalytic C–H Functionalization Methods
- Type
- article
- Field-Weighted Citation Impact
- 0.00