Metal-free photocatalysts for the oxidation of non-activated alcohols and the oxygenation of tertiary amines performed in air or oxygen

Abstract

This protocol describes the use of 9-fluorenone as a cheap and non-toxic photocatalyst for the oxidation of non-activated alcohols performed under the irradiation of a blue light-emitting diode. It also describes the use of the similarly cheap and non-toxic photocatalyst rose bengal for the selective α-oxygenation of tertiary amines to produce the corresponding amides in a selective way using the same light source. We have provided detailed instructions on how to assemble the light-emitting diode equipment and set up the photocatalytic reaction, where an oxygen atmosphere is created with an O2-filled balloon. Further details are provided using four example reactions that illustrate how this system works: alcohol oxidation to prepare terephthlalaldehyde and androstanedione, and amine oxidation to make 2-phenyl-3,4-dihydroisoquinolin-1(2H)-one and (4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)m-tolyl)methanone. The times needed to perform these photocatalytic reactions are 18, 76, 22 and 54 h, respectively. We believe that this protocol represents a robust methodology for the late-stage modification of amines and the selective oxidation of steroids.

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Fig. 1: Oxidation of benzyl alcohol to benzaldehyde and α-oxygenation of 1-benzylpiperidine to 1-benzoylpiperidine as example applications of the present protocol.
Fig. 2: Pros and cons of different approaches to the catalytic oxidation of alcohols.
Fig. 3: Pros and cons of different approaches to the catalytic α-oxygenation of tertiary amines.
Fig. 4: Substrate scope for the oxidation of primary and secondary alcohols and steroids.
Fig. 5: Substrate scope of the visible-light-mediated α-oxygenation of tertiary amines.
Fig. 6
Fig. 7
Fig. 8: Photograph of the apparatus for performing four reactions in parallel.
Fig. 9: Photographs illustrating Steps 1, 2 and 3 of the Procedure.

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Acknowledgements

We are very thankful to Prof. Dr. Lutz Ackermann for the kind support behind our work. We thank Fonds der Chemischen Industrie (FCI, Liebig-Fellowship to S.D.) and Chinese Scholarship Council (CSC funding to Y.Z.) for the financial support.

Author information

Y.Z., W.S., D.R. and S.D. planned the original project. W.S. and Y.Z. performed the catalytic reactions in the protocol. Y.Z., W.S. and S.D. wrote the protocol.

Correspondence to Shoubhik Das.

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The authors declare no competing interests.

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Key reference(s) using this protocol

Zhang, Y., Riemer, D., Schilling, W., Kollman, J. & Das, S. ACS Catal. 8, 6659–6664 (2018): https://doi.org/10.1021/acscatal.8b01897

Schilling, W., Riemer, D., Zhang, Y., Hatami, N. & Das, S. et al. ACS Catal. 8, 5425–5430 (2018): https://doi.org/10.1021/acscatal.8b01067

Integrated supplementary information

Supplementary Fig. 1 Measurement of wavelength about blue LED.

The emission spectra of the light setup was measured with a UV-visible probe from Ocean optics (P200-5-UV-Vis). The emission spectra showed a clear wavelength band between 404 and 553 nm with a maximum at 456 nm.

Supplementary Fig. 2 Yield of fluorenone-catalyzed alcohol oxidation based on light intensity.

Reaction conditions: benzyl alcohol (0.29 mmol), photocatalysts (3 mol%), solvent (1 ml), O2 (balloon) or air, room temperature (r.t.), 18 h. Yield determined by GC using n-dodecane as an internal standard.

Supplementary Fig. 3 Yield of fluorenone-catalyzed alcohol oxidation based on light intensity.

Reaction conditions: benzyl alcohol (0.29 mmol), photocatalysts (3 mol%), solvent (1 ml), O2 (balloon) or air, room temperature (r.t.), 14 h. Yield determined by GC using n-dodecane as an internal standard.

Supplementary Fig. 4 Yields of rose bengal–catalyzed oxygenation of amines based on light intensity.

Reaction conditions: O2 (balloon), 0.3 mmol 1-benzylpiperidine, photocatalyst (3 mol%), 0.45 mmol DBN, 2.5 ml solvent, room temperature, 16 h.

Supplementary Fig. 5

Proposed mechanism of alcohol oxidation.

Supplementary Fig. 6

Proposed mechanism of oxygenation of tertiary amines.

Supplementary information

Supplementary Information

Supplementary Figs. 1–6, Supplementary Table 1 and Supplementary Methods.

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Zhang, Y., Schilling, W., Riemer, D. et al. Metal-free photocatalysts for the oxidation of non-activated alcohols and the oxygenation of tertiary amines performed in air or oxygen. Nat Protoc (2020). https://doi.org/10.1038/s41596-019-0268-x

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