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Photoinduced, Copper-Catalyzed Alkylation of Amides with Unactivated Secondary Alkyl Halides at Room Temperature

Do, Hien-Quang and Bachman, Shoshana and Bissember, Alex C. and Peters, Jonas C. and Fu, Gregory C. (2014) 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. http://resolver.caltech.edu/CaltechAUTHORS:20140127-095430890

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Abstract

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:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/ja4126609DOIArticle
http://pubs.acs.org/doi/abs/10.1021/ja4126609PublisherArticle
ORCID:
AuthorORCID
Peters, Jonas C.0000-0002-6610-4414
Fu, Gregory C.0000-0002-0927-680X
Additional Information:© 2014 American Chemical Society. Received: December 12, 2013. Publication Date (Web): January 21, 2014. This work was supported by the Gordon and Betty Moore Foundation. We acknowledge Prof. Rick L. Danheiser (MIT) for helpful discussions, and we thank Trixia M. Buscagan, Sidney E. Creutz, Gregory P. Harlow, Dr. Nathan D. Schley, Dr. David VanderVelde (Caltech NMR Facility), and Dr. Scott C. Virgil (Caltech Center for Catalysis and Chemical Synthesis, supported by the Gordon and Betty Moore Foundation) for experimental assistance.
Funders:
Funding AgencyGrant Number
Gordon and Betty Moore FoundationUNSPECIFIED
Record Number:CaltechAUTHORS:20140127-095430890
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20140127-095430890
Official Citation:Photoinduced, Copper-Catalyzed Alkylation of Amides with Unactivated Secondary Alkyl Halides at Room Temperature Hien-Quang Do, Shoshana Bachman, Alex C. Bissember, Jonas C. Peters, and Gregory C. Fu Journal of the American Chemical Society 2014 136 (5), 2162-2167
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:43521
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:27 Jan 2014 21:01
Last Modified:12 Dec 2016 21:04

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