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Photoinduced, copper-catalyzed alkylation of amides with unactivated secondary alkyl halides at room temperature

journal contribution
posted on 2023-05-17, 22:29 authored by Do, H-Q, Bachman, S, Alexander BissemberAlexander Bissember, Peters, JC, Fu, GC
The development of a mild and general method for the alkylation of amides with relatively unreactive alkyl halides (i.e., poor substrates for SN2 reactions) is an ongoing challenge in organic synthesis. We describe herein a versatile transition-metal-catalyzed approach: in particular, a photoinduced, copper-catalyzed monoalkylation of primary amides. A broad array of alkyl and aryl amides (as well as a lactam and a 2-oxazolidinone) couple with unactivated secondary (and hindered primary) alkyl bromides and iodides using a single set of comparatively simple and mild conditions: inexpensive CuI as the catalyst, no separate added ligand, and C−N bond formation at room temperature. The method is compatible with a variety of functional groups, such as an olefin, a carbamate, a thiophene, and a pyridine, and it has been applied to the synthesis of an opioid receptor antagonist. A range of mechanistic observations, including reactivity and stereochemical studies, are consistent with a coupling pathway that includes photoexcitation of a copper−amidate complex, followed by electron transfer to form an alkyl radical.


Publication title

Journal of the American Chemical Society










School of Natural Sciences


Amer Chemical Soc

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1155 16Th St, Nw, Washington, USA, Dc, 20036

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Copyright 2014 American Chemical Society

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