Organic Letters
Letter
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Scheme 7. Possible Reaction Mechanism
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oxidize HBr in the presence of oxygen to give Br2.17d
Sequentially, the α-bromination of ketone 1ab should occur by
Br2 generated in situ, and the nucleophilic substitution of α-
bromo ketone with morpholine will produce α-amino ketone
3aa. However, a detailed mechanistic study of this new one-pot
synthesis and the asymmetric version of this methodology with
organocatalysis is underway.
In summary, we have developed a novel approach to the
synthesis of medicinally important α-amino ketones starting with
readily available benzylic secondary alcohols using N-bromo-
succinimide at ambient temperature without any additional
oxidants. This reaction proceeds via three consecutive steps such
as oxidation of alcohols, α-bromination of ketones, and
nucleophilic substitution of α-bromo ketones to give α-amino
ketones. Importantly, this novel one-pot reaction avoids direct
usage of toxic and corrosive bromine as it is generated in situ in
the reaction and be utilized. This methodology has delivered
pharmaceutical agents such as amfepramone and pyrovalerone in
good yields.
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(11) See the Supporting Information for detailed optimization.
(12) The benzylic secondary alcohols are easily synthesized from the
Grignard reaction of aryl bromides with various aldehydes.
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5124.
ASSOCIATED CONTENT
* Supporting Information
Detailed experimental procedures, characterization data, and
copies of NMR spectra are given. This material is available free of
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AUTHOR INFORMATION
Corresponding Author
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Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
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We thank the DST New Delhi (Project No. SB/S1/OC-72/
2013) for financial support for this project. S.G thanks CSIR,
New Delhi for a JRF. Dr. V. Rajeshkumar thanks IITM for an
institute postdoctoral fellowship. S.S.K. thanks CSIR for an SRF.
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