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


Do, H-Q and Bachman, S and Bissember, AC and Peters, JC and Fu, GC, Photoinduced, copper-catalyzed alkylation of amides with unactivated secondary alkyl halides at room temperature, Journal of the American Chemical Society, 136, (5) pp. 2162-2167. ISSN 0002-7863 (2014) [Refereed Article]

Copyright Statement

Copyright 2014 American Chemical Society

DOI: doi:10.1021/ja4126609


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.

Item Details

Item Type:Refereed Article
Research Division:Chemical Sciences
Research Group:Organic chemistry
Research Field:Organic chemical synthesis
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the chemical sciences
UTAS Author:Bissember, AC (Associate Professor Alex Bissember)
ID Code:89088
Year Published:2014
Web of Science® Times Cited:154
Deposited By:Chemistry
Deposited On:2014-02-25
Last Modified:2017-10-25

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