Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Dec 15;7(51):48564-48571.
doi: 10.1021/acsomega.2c07172. eCollection 2022 Dec 27.

Visible-Light-Driven Solventylation Strategy for Olefin Functionalization

Pietro Capurro  1 , Valentina Ricciardiello  1 , Paola Lova  1 , Chiara Lambruschini  1 , Stefano Protti  2 , Andrea Basso  1
Affiliations

Visible-Light-Driven Solventylation Strategy for Olefin Functionalization

Pietro Capurro et al. ACS Omega. .

Abstract

Amphiphilic aryl radicals generated upon visible light irradiation of arylazo sulfones have been exploited in the development of a solventylation strategy via hydrogen atom transfer (HAT). The present protocol succeeded in the versatile functionalization of various olefins with carbon-centered radicals deriving from acetone, acetonitrile, chloroform, methylene chloride, nitromethane, methyl acetate, and methyl formate under metal- and photocatalyst-free conditions. The direct addition of the aryl radicals onto the olefin substrates was suppressed under high dilution conditions.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. (a) Functionalization of Olefins Exploiting Aryl Radical-Induced HAT from Acetone Optimized by Our Group
Conditions: 4-MeOPhN2BF4 (1 equiv), Ru(bpy)3Cl2 (1 mol %), acetone 0.01 M, 450 nm flow; (b) envisioned photochemical activation of the solvent via arylazo sulfones as aryl radical precursors and subsequent olefin functionalization.
Scheme 2
Scheme 2. Optimization of the Acetonylation Reaction Using Azosulfones.
For details of the reaction conditions, see Table 1.
Scheme 3
Scheme 3. Investigation of the Solvent Scope using Acrylamide 1a under Optimized Conditions (Top)
Solventylation reactions with acrylamides 1b–1d and olefin 1e (bottom). Yields are referred to isolated products after column chromatography. Yields in brackets are referred to by-products 4a–4e.
Scheme 4
Scheme 4. Solventylation Reaction with Silyl Enolethers 1f–1i
Yields are referred to isolated products after column chromatography. K2S2O8 (2 equiv) used as an oxidant. BAIB (2 equiv) used as an oxidant. Obtained after elimination with Et3N (2 equiv).
Scheme 5
Scheme 5. Use of the Solventylation Protocol for the Preparation of an Advanced Intermediate in the Synthesis of Esermethole
Conditions: (a) 2a (1 equiv, 0.01 M), K2S2O8 (2 equiv), MeNO2, HP LEDs 450 nm (0.6 W), overnight (b) Fe (5 equiv), HCl 6 M:MeOH 1:1 (0.33 M), 110 °C, 3 h.
Scheme 6
Scheme 6. Outcome of the Solventylation Reaction of 1a with Acetonitrile under Concentrated (0.1 M) Conditions
Yields are referred to isolated products after column chromatography.
See this image and copyright information in PMC

References

    1. See for review:

    2. Guillemard L.; Kaplaneris N.; Ackermann L.; Johansson M. J. Late-stage C–H functionalization offers new opportunities in drug discovery. Nat. Rev. Chem. 2021, 5, 522–545. 10.1038/s41570-021-00300-6. - DOI - PubMed
    3. Börgel J.; Ritter T. Late-stage functionalization. Chem 2020, 6, 1877–1887. 10.1016/j.chempr.2020.07.007. - DOI
    4. Baudoin O. Multiple catalytic C–H Bond Functionalization for Natural Product Synthesis. Angew. Chem., Int. Ed. 2020, 59, 17798–17809. 10.1002/anie.202001224. - DOI - PubMed

    1. See for review:

    2. Capaldo L.; Quadri L.; Ravelli D. Photocatalytic hydrogen atom transfer: the philosopher’s stone for late-stage functionalization?. Green Chem. 2020, 22, 3376–3396. 10.1039/D0CS00493F. - DOI
    3. Cannalire R.; Pelliccia S.; Sancineto L.; Novellino E.; Tron G. C.; Giustiniano M. Visible light photocatalysis in the late-stage functionalization of pharmaceutically relevant compounds. Chem. Soc. Rev. 2021, 50, 766–897. 10.1039/D0CS00493F. - DOI - PubMed
    1. Murray P. R. D.; Cox J. H.; Chiappini D. N.; Roos C. B.; McLoughlin E. A.; Hejna B. G.; Nguyen S. T.; Ripberger H. H.; Ganley J. M.; Tsui E.; Shin N. Y.; Koronkiewicz B.; Qiu G.; Knowles R. R. Photochemical and Electrochemical Applications of Proton-Coupled Electron Transfer in Organic Synthesis. Chem. Rev. 2022, 122, 2017–2291. 10.1021/acs.chemrev.1c00374. - DOI - PMC - PubMed
    1. Capaldo L.; Ravelli D.; Fagnoni M. Direct Photocatalyzed Hydrogen Atom Transfer (HAT) for Aliphatic C–H Bonds Elaboration. Chem. Rev. 2022, 122, 1875–1924. 10.1021/acs.chemrev.1c00263. - DOI - PMC - PubMed
    1. Crespi S.; Fagnoni M. Generation of Alkyl Radicals: From the Tyranny of Tin to the Photon Democracy. Chem. Rev. 2020, 120, 9790–9833. 10.1021/acs.chemrev.0c00278. - DOI - PMC - PubMed