" Rhodium Nitrene " and selective C(sp3)-H bond amination. Iron and hydroxylamine : a long-lasting couple for amination reactions

Abstract of Philippe Dauban's talk

" Rhodium Nitrene and selective C(sp3)-H bond amination

The paradigm of a spectator C-H bond in synthesis has been outdated since the emergence of catalytic C-H functionalization reactions. However, these reactions pose challenges in terms of selectivity, as any molecule possessing a large number bonds C-H of very similar reactivity, how do you selectively convert just one of these bonds ? Several strategies have been developed to control the selectivity of C-H functionalization reactions, 1) by designing directed processes, which include C-H activation processes or intramolecular reactions, or 2) by taking advantage of the electronic/steric properties of organic compounds^.1 Although effective and selective, these substrate-controlled reactions have their limitations, particularly with regard to unactivated C-H bonds, which often remain inaccessible (BDE > 95 kcal.mol-1).

One solution to overcome these limitations is based on the concept of " catalyst-controlled selectivity " ², which is possible with " rhodium nitrenes ". These are highly electrophilic nitrogen species that enable electron-rich C(sp3)-H bonds (e.g. benzylic C-H bonds) to be converted into C-N bonds. However, the selectivity of these C-H amination reactions can be tuned by modifying the structure of the catalytic species. In this lecture, we will discuss our latest results on the selective amination of different classes of C-H bonds (from benzylic to non-activated bonds), which were made possible by the discovery of highly discriminating rhodium nitrenes^.3

1. a) Chu, J.C.K.; Rovis, T., Angew. Chem. Int. Ed. 2018, 57, 62. b) Newhouse, T.; Baran, P.S., Angew. Chem. Int. Ed. 2011, 50, 3362.
2. a) Hartwig, J.F.; Larsen, M.A. ACS Cent. Sci. 2016, 2, 281. b) Jiao, Y.; Chen, X.-Y.; Stoddart, J.F., Chem. 2022, 8, 414. c) E. Brunard, V. Boquet, T. Saget, E.D. Sosa Carrizo, M. Sircoglou, P. Dauban, Synlett 2025, 36, 630.
3. a) A. Nasrallah, V. Boquet, A. Hecker, P. Retailleau, B. Darses, P. Dauban, Angew. Chem. Int. Ed. 2019, 58, 8192. b) A. Nasrallah, Y. Lazib, V. Boquet, B. Darses, P. Dauban, Org. Process Res. Dev. 2020, 24, 724. c) E. Brunard, V. Boquet, E. Van Elslande, T. Saget, P. Dauban, J. Am. Chem. Soc. 2021, 143, 6407. e) V. Boquet, A. Nasrallah, A. L. Dana, E. Brunard, P. H. Di Chenna, F. J. Duran, P. Retailleau, B. Darses, M. Sircoglou, P. Dauban, J. Am. Chem. Soc. 2022, 144, 17156. f) E. Brunard, V. Boquet, T. Saget, E.D. Sosa Carrizo, M. Sircoglou, P. Dauban, J. Am. Chem. Soc. 2024, 146, 5843. g) T. Bissonnier, E. Brunard, M. Andresini, S. Poyer, T. Saget, P. Dauban, J. Am. Chem. Soc. 2025, 147, 24684.

Abstract from Guillaume Prestat's talk

Iron and hydroxylamine : a durable couple for amination reactions

Transition metal-catalyzed nitrene transfer reactions are a powerful strategy for the formation of nitrogen-containing molecules. Over the years, various catalytic systems have been developed, mainly based on rhodium, ruthenium, iridium or copper complexes, and mostly using iminoiodinanes as nitrene precursors. The reaction efficiency of these systems is remarkable, and in particular the rhodium/iminoiodinane pair achieves exceptional enantioselectivity values. However, the use of these rare transition metals and iminoiodinanes is problematic in terms of durability and toxicity. The combination of iron with hydroxylamine derivatives represents a promising solution for the development of new sustainable processes. Iron has extremely low toxicity, and its high abundance in the earth's crust guarantees sustainable access to a wide variety of inexpensive salts. Hydroxylamine derivatives can be synthesized efficiently from hydroxylamine by simple and cost-effective procedures, and generate metal-nitride species without the addition of external oxidants. Our research group is focusing its efforts on developing sustainable methods based on the use of the iron/hydroxylamine couple. We will present our results for aziridination reactions, intra- and intermolecular difunctionalization of alkenes, and direct functionalization of C-H bonds.