Copper-Catalyzed Alkylation of Aliphatic Amines Induced by Visible Light
Abstract
Although the alkylation of an amine by an alkyl halide serves as a "textbook example" of a nucleophilic substitution reaction, the selective mono-alkylation of aliphatic amines by unactivated, hindered halides persists as a largely unsolved challenge in organic synthesis. We report herein that primary aliphatic amines can be cleanly mono-alkylated by unactivated secondary alkyl iodides in the presence of visible light and a copper catalyst. The method operates under mild conditions (–10 °C), displays good functional-group compatibility, and employs commercially available catalyst components. A trapping experiment with TEMPO is consistent with C–N bond formation via an alkyl radical in an out-of-cage process.
Additional Information
© 2017 American Chemical Society. Received: September 7, 2017; Published: November 28, 2017. Support has been provided by the National Institutes of Health (National Institute of General Medical Sciences, grant R01-GM109194) and the Alexander von Humboldt Foundation (fellowship for J.S.). We thank Jun Myun Ahn, Bradley J. Gorsline, Dr. Paul H. Oyala (Caltech EPR Facility, supported by National Science Foundation grant NSF-1531940), Dr. Mona Shahgholi (Caltech Mass Spectrometry Facility), Dr. Yichen Tan, Dr. David G. VanderVelde (Caltech NMR Facility), and Dr. Scott C. Virgil (Caltech Center for Catalysis and Chemical Synthesis) for assistance and helpful discussions. The authors declare no competing financial interest.Attached Files
Accepted Version - nihms-978051.pdf
Supplemental Material - ja7b09582_si_001.pdf
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Additional details
- PMCID
- PMC6044445
- Eprint ID
- 83538
- Resolver ID
- CaltechAUTHORS:20171128-135738544
- NIH
- R01-GM109194
- Alexander von Humboldt Foundation
- NSF
- CHE-1531940
- Created
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2017-11-28Created from EPrint's datestamp field
- Updated
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2022-03-21Created from EPrint's last_modified field