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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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.
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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.
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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.
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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 15, 822–839 (2020). https://doi.org/10.1038/s41596-019-0268-x
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DOI: https://doi.org/10.1038/s41596-019-0268-x
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