Amines are a quintessential moiety in bioactive molecules, pharmaceuticals and organic materials. Transition-metal-catalysed C–N coupling of aryl electrophiles has been established as a powerful and reliable method for amine synthesis. However, the analogous C–N coupling of alkyl electrophiles is largely under-developed due to the decomposition of metal alkyl intermediates by β-hydrogen elimination and difficulty in C(sp3)–N reductive elimination. Here, we provide a general strategy for amination of alkyl electrophiles by merging photoredox and copper catalysis. Photoredox catalysis allows the use of alkyl redox-active esters, recently established as a superior class of alkyl electrophiles, whereas copper catalysis enables C(sp3)–N cross-coupling. Decarboxylative amination can be used for the synthesis of a diverse set of alkyl anilines with high chemoselectivity and functional-group compatibility. Rapid functionalization of amino acids, natural products and drugs is demonstrated.
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This work is supported by the NoNoMeCat Marie Skłodowska-Curie training network funded by the European Union under the Horizon 2020 Programme (675020-MSCA-ITN-2015-ETN). We thank R. Scopelliti (École Polytechnique Fédérale de Lausanne) for assistance with X-ray crystallography of 9a.
The authors declare no competing financial interests.
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Mao, R., Frey, A., Balon, J. et al. Decarboxylative C(sp3)–N cross-coupling via synergetic photoredox and copper catalysis. Nat Catal 1, 120–126 (2018). https://doi.org/10.1038/s41929-017-0023-z
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