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. 2011 Oct 26;133(42):16901-10.
doi: 10.1021/ja206230h. Epub 2011 Oct 3.

Highly practical copper(I)/TEMPO catalyst system for chemoselective aerobic oxidation of primary alcohols

Jessica M Hoover  1 , Shannon S Stahl
Affiliations

Highly practical copper(I)/TEMPO catalyst system for chemoselective aerobic oxidation of primary alcohols

Jessica M Hoover et al. J Am Chem Soc. .

Abstract

Aerobic oxidation reactions have been the focus of considerable attention, but their use in mainstream organic chemistry has been constrained by limitations in their synthetic scope and by practical factors, such as the use of pure O(2) as the oxidant or complex catalyst synthesis. Here, we report a new (bpy)Cu(I)/TEMPO catalyst system that enables efficient and selective aerobic oxidation of a broad range of primary alcohols, including allylic, benzylic, and aliphatic derivatives, to the corresponding aldehydes using readily available reagents, at room temperature with ambient air as the oxidant. The catalyst system is compatible with a wide range of functional groups and the high selectivity for 1° alcohols enables selective oxidation of diols that lack protecting groups.

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Figures

Figure 1
Figure 1
Comparison of three different Cu/TEMPO catalyst systems in the aerobic oxidation of 1-octanol (1.0 mmol) at 27 °C. Catalyst systems include the following: (a) “Sheldon conditions” (similar to Table 1, entry 2): CuBr2 (5 mol %), bpy (5 mol %), TEMPO (5 mol %), and KOtBu (5 mol %) in 2:1 MeCN:H2O (0.67 M) (formula image, green); (b) “Semmelhack conditions” (similar to Table 1, entry 1): CuCl (10 mol %) and TEMPO (10 mol %) in DMF (0.4 M) (formula image, red); and (c) Cu(OTf) (5 mol %), bpy (5 mol %), TEMPO (5 mol %), and NMI (10 mol %) in MeCN (0.2 M) (formula image, blue). See the Supporting Information for additional details.
Figure 2
Figure 2
Effect of Cu source on the rate of aerobic oxidation of benzyl alcohol (0.5 mmol) at 27 °C. The Cu source (5 mol %) was combined with TEMPO (5 mol %), NMI (10 mol %), and bpy (5 mol %) with [Cu] = (a) CuBr2 (formula image, green), (b) Cu(OTf)2 (formula image, black), and (c) CuBr (formula image, red), and (d) Cu(OTf) (formula image, blue). Reactions employing CuBr2 consistently exhibit a long induction period. See the Supporting Information for additional details.
Figure 3
Figure 3
Limitations of (bpy)CuI/TEMPO oxidation system due to (A) overoxidation and (B) inhibited oxidation.
Chart 1
Chart 1
Unprotected Diol Substrates Examined for Selective Oxidation.
Scheme 1
Scheme 1
Representative Catalyst Systems for Aerobic Oxidation of Primary Alcohols.
See this image and copyright information in PMC

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References

    1. Tojo G, Fernández M. Basic Reactions in Organic Synthesis. Springer; New York: 2010. Oxidation of Alcohols to Aldehydes and Ketones.
    2. Tojo G, Fernández M. Basic Reactions in Organic Synthesis. Spriner; New York: 2010. Oxidation of Primary Alcohols to Carboxylic Acids.
    1. Bowden K, Heilbron IM, Jones ERH, Weedon BC. J. Chem. Soc. 1946:39–45.
    2. Corey EJ, Suggs JW. Tetrahedron Lett. 1975;16:2647–2650.
    3. Piancatelli G, Scettri A, D’Auria M. Synthesis. 1982:245–258.
    4. De A. J. Sci. Ind. Res. 1982;41:484–494.
    5. Luzzio FA, Guziec FS. Org. Prep. Proced. Int. 1988;20:533–584.
    1. Ladbury JW, Cullis CF. Chem Rev. 1958;58:403–438.
    2. Fatiadi AJ. Synthesis. 1976:65–104.
    3. Taylor RJK, Reid M, Foot J, Raw SA. Acc. Chem. Res. 2005;38:851–869. - PubMed
    1. Pfitzner KE, Moffatt JG. J. Am. Chem. Soc. 1963;85:3027–3028.
    2. Mancuso AJ, Huang S-L, Swern D. J. Org. Chem. 1978;43:2480–2482.
    3. Mancuso AJ, Brownfain DS, Swern D. J. Org. Chem. 1979;44:4148–4150.
    4. Tidwell TT. Synthesis. 1990:857–870.
    1. Dess DB, Martin JC. J. Org. Chem. 1983;48:4155–4156.
    2. Frigerio M, Santagostino M. Tetrahedron Lett. 1994;35:8019–8022.
    3. Uyanik M, Ishihara K. Chem. Commun. 2009:2086–2099. - PubMed

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