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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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.
The authors declare no competing interests.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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
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.
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.
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.
Proposed mechanism of alcohol oxidation.
Proposed mechanism of oxygenation of tertiary amines.
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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