The development of a mild and general method for the alkylation of amides with relatively unreactive alkyl halides (i.e., poor substrates for S_N2 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 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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