Unified synthesis of unconventional α-polyhalogenated amines through hydroaminoalkylation
Hofmeister AK, Iannelli G, Angyal P, Malandain A, Kaiser D, Maryasin B, Kählig H, Barel M, Novarino G, Maulide N. 2026. Unified synthesis of unconventional α-polyhalogenated amines through hydroaminoalkylation. Angewandte Chemie International Edition., e1233707.
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Journal Article
| Epub ahead of print
| English
Scopus indexed
Author
Hofmeister, Angela K.;
Iannelli, Giulia;
Angyal, Péter;
Malandain, Augustin;
Kaiser, Daniel;
Maryasin, Boris;
Kählig, Hanspeter;
Barel, MatteoISTA;
Novarino, GaiaISTA 
;
Maulide, Nuno
;
Maulide, NunoDepartment
Abstract
We report a unified method for the synthesis of α-polyhalomethyl amines from alkenes and alkynes, enabled by readily available hemiaminal reagents. This operationally simple transformation allows for the introduction of not only well-established CF3 and CF2H groups, but also the synthetically (and medicinally) underexplored CF2Cl and CFClH motifs—thereby broadening access to previously inaccessible chemical space of halogenated amine scaffolds. The method displays broad substrate scope and functional-group tolerance while operating under mild conditions. Late-stage functionalization of drug-like derivatives of Oxaprozin, Erlotinib, and Ibuprofen (among others) is reported.
Publishing Year
Date Published
2026-07-10
Journal Title
Angewandte Chemie International Edition
Publisher
Wiley
Acknowledgement
Funded by the European Union (ERC, C-HANCE, 101142915 to N.M.). Views and opinions expressed are, however, those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Council. This research was funded in full or in part by the Austrian Science Fund (FWF, 10.55776/P37182 to N.M.). The technical staff of the NMR Centre of the Faculty of Chemistry (University of Vienna) are acknowledged for crucial NMR measurements and expert advice with spectral analysis. The authors thank the Core Facility Crystal Structure Analysis (U. Vienna) for determination of the crystal structures. The authors are also grateful to the University of Vienna for its continued support of our research programs.
Open Access funding provided by Universität Wien.
Article Number
e1233707
ISSN
eISSN
IST-REx-ID
Cite this
Hofmeister AK, Iannelli G, Angyal P, et al. Unified synthesis of unconventional α-polyhalogenated amines through hydroaminoalkylation. Angewandte Chemie International Edition. 2026. doi:10.1002/anie.1233707
Hofmeister, A. K., Iannelli, G., Angyal, P., Malandain, A., Kaiser, D., Maryasin, B., … Maulide, N. (2026). Unified synthesis of unconventional α-polyhalogenated amines through hydroaminoalkylation. Angewandte Chemie International Edition. Wiley. https://doi.org/10.1002/anie.1233707
Hofmeister, Angela K., Giulia Iannelli, Péter Angyal, Augustin Malandain, Daniel Kaiser, Boris Maryasin, Hanspeter Kählig, Matteo Barel, Gaia Novarino, and Nuno Maulide. “Unified Synthesis of Unconventional α-Polyhalogenated Amines through Hydroaminoalkylation.” Angewandte Chemie International Edition. Wiley, 2026. https://doi.org/10.1002/anie.1233707.
A. K. Hofmeister et al., “Unified synthesis of unconventional α-polyhalogenated amines through hydroaminoalkylation,” Angewandte Chemie International Edition. Wiley, 2026.
Hofmeister AK, Iannelli G, Angyal P, Malandain A, Kaiser D, Maryasin B, Kählig H, Barel M, Novarino G, Maulide N. 2026. Unified synthesis of unconventional α-polyhalogenated amines through hydroaminoalkylation. Angewandte Chemie International Edition., e1233707.
Hofmeister, Angela K., et al. “Unified Synthesis of Unconventional α-Polyhalogenated Amines through Hydroaminoalkylation.” Angewandte Chemie International Edition, e1233707, Wiley, 2026, doi:10.1002/anie.1233707.
PMID: 42429166
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