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Copper(I)/TEMPO-catalyzed aerobic oxidation of primary alcohols to aldehydes with ambient air

Nature Protocols volume 7, pages 1161–1166 (2012)Cite this article

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Abstract

This protocol describes a practical laboratory-scale method for aerobic oxidation of primary alcohols to aldehydes, using a chemoselective CuI/TEMPO (TEMPO = 2,2,6,6-tetramethyl-1-piperidinyloxyl) catalyst system. The catalyst is prepared in situ from commercially available reagents, and the reactions are performed in a common organic solvent (acetonitrile) with ambient air as the oxidant. Three different reaction conditions and three procedures for the isolation and purification of the aldehyde product are presented. The oxidations of eight different alcohols, described here, include representative examples of each reaction condition and purification method. Reaction times vary from 20 min to 24 h, depending on the alcohol, whereas the purification methods each take about 2 h. The total time necessary for the complete protocol ranges from 3 to 26 h.

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Figure 1
Figure 2: Reaction conditions.
Figure 3: Purification conditions.

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Acknowledgements

We thank Buzz Meade Photography for photographs in Figures 2 and 3. We are grateful to the US National Institutes of Health (NIH) (RC1-GM091161), the American Chemical Society Green Chemistry Institute Pharmaceutical Roundtable and the National Science Foundation (NSF) (Graduate Research Fellowship for J.E.S.). NMR spectroscopy facilities were partially supported by the NSF (CHE-9208463) and NIH (S10 RR08389).

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Authors and Affiliations

  1. Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA

    Jessica M Hoover, Janelle E Steves & Shannon S Stahl

Authors
  1. Jessica M Hoover
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  2. Janelle E Steves
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  3. Shannon S Stahl
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Contributions

J.M.H. developed the catalyst system described here and performed the experimental work described here. J.E.S. confirmed the reproducibility of experimental procedures and performed the oxidation reaction and product characterization for Table 1 (entry 3). S.S.S. conceived and supervised the project. Manuscript assembly was completed by J.M.H., with assistance by J.E.S. and S.S.S.

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Correspondence to Shannon S Stahl.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Methods

Detailed procedure for 10 mmol scale oxidation reaction. (PDF 94 kb)

Supplementary Figure 1

Influence of added H2O on the oxidation of benzyl alcohol by CuI/TEMPO. (PDF 247 kb)

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Hoover, J., Steves, J. & Stahl, S. Copper(I)/TEMPO-catalyzed aerobic oxidation of primary alcohols to aldehydes with ambient air. Nat Protoc 7, 1161–1166 (2012). https://doi.org/10.1038/nprot.2012.057

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