Abstract
Photoinduced C(sp3)–H functionalization through hydrogen atom transfer (HAT) processes is pivotal in organic synthesis because of the mild reaction conditions and applicability to late-stage functionalization of complex molecules, such as pharmaceuticals and agrochemicals. Despite promise, achieving precise site-selectivity and overcoming the high bond dissociation energy (BDE) of unactivated aliphatic C–H bonds in photoinduced C(sp3)–H functionalization reactions, through HAT, are challenging. In this landscape, pyridine N-oxides have emerged as potent HAT reagents due to their easily tunable nature. This Perspective highlights studies showcasing the potential of pyridine N-oxides as HAT reagents in site-selective hydrogen atom abstraction from unactivated C(sp3)–H bonds and explores their structure–activity relationship with multiple hydrocarbon substrates. Pyridine N-oxides have become promising reagents in environmentally friendly synthesis owing to their cost-effectiveness, tunability and applicability in (heterogeneous) catalysis. Ongoing research on the use of pyridine N-oxides as HAT reagents will probably offer additional avenues for efficient and selective C(sp3)–H bond functionalization.
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Acknowledgements
J.W. acknowledges financial support provided by the National Research Foundation, the Prime Minister’s Office of Singapore, under its NRF-CRP Programme (award no. NRFCRP25-2020RS-0002), Pfizer (A-8000004-00-00) and the NUS (Chongqing) Research Institute, National Natural Science Foundation of China (grant nos. 22071170 and 22371200). D.R. acknowledges support from the Ministero dell’Università e della Ricerca (MUR) and the University of Pavia through the program ‘Dipartimenti di Eccellenza 2023–2027’.
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Ang, H.T., Miao, Y., Ravelli, D. et al. Pyridine N-oxides as hydrogen atom transfer reagents for site-selective photoinduced C(sp3)–H functionalization. Nat. Synth 3, 568–575 (2024). https://doi.org/10.1038/s44160-024-00528-2
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DOI: https://doi.org/10.1038/s44160-024-00528-2