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Nitrene transfer catalysts for enantioselective C–N bond formation

Abstract

Transition-metal-catalysed, non-enzymatic transformations of C–H and C=C bonds to C–N bonds through nitrene transfer (NT) are powerful synthetic tools to prepare valuable amine building blocks. Although the first examples of racemic NT were reported more than 50 years ago, catalysts that mediate enantioselective NT with a broad substrate scope have been slow to emerge. However, the past ten years have seen the discovery of several first-row, second-row and third-row transition metal catalysts for asymmetric NT. This Review covers recent developments in asymmetric aziridination and C–H bond amination reactions. We describe catalyst design principles, re-evaluate traditional catalyst architectures, show how the scope of nitrene precursors has expanded and present new mechanistic insights. Following this, we highlight remaining opportunities and challenges to developing more practical and general synthetic methodologies. Realizing chemoselective, site-selective and enantioselective intermolecular NT will streamline amine synthesis and allow us to explore new chemical space.

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Fig. 1: Classical reactions of metal–nitrenes and some catalysts with which they are realized.
Fig. 2: Asymmetric nitrene transfer reactions catalysed by Co complexes of D2-symmetric porphyrins.
Fig. 3: Metal–salen complexes catalyse asymmetric nitrene transfer.
Fig. 4: Dirhodium tetracarboxylates and tetracarboxamidates catalyse asymmetric nitrene transfer.
Fig. 5: Metal complexes of bis(oxazoline) ligands catalyse asymmetric nitrene transfer.
Fig. 6: Chiral half-sandwich complexes for asymmetric nitrene transfer.
Fig. 7: Chiral-at-metal complexes in asymmetric nitrene transfer.

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Acknowledgements

E. Zerull, J. Kim and T. A. Trinh are thanked for their helpful comments during the editing of this manuscript. J.M.S. is grateful to the NSF (Award number 1664374) for financial support for this research.

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M.J. researched data for the article and contributed to the content and writing of the manuscript. J.M.S. contributed to the discussion, writing and reviewing/editing the manuscript before submission.

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Ju, M., Schomaker, J.M. Nitrene transfer catalysts for enantioselective C–N bond formation. Nat Rev Chem 5, 580–594 (2021). https://doi.org/10.1038/s41570-021-00291-4

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