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. 2025 Feb 28;27(8):2011-2015.
doi: 10.1021/acs.orglett.5c00389. Epub 2025 Feb 20.

Merging Photoexcited Nitroarenes with Lewis Acid Catalysis for the Anti-Markovnikov Oxidation of Alkenes

Joshua M Paolillo  1 , Mahmoud R Saleh  1 , Ethan W Junk  1 , Marvin Parasram  1
Affiliations

Merging Photoexcited Nitroarenes with Lewis Acid Catalysis for the Anti-Markovnikov Oxidation of Alkenes

Joshua M Paolillo et al. Org Lett. .

Abstract

Herein we describe the oxidation of alkenes to carbonyls and acetonides via the interplay of photoexcited nitroarenes and Lewis acid catalysis. A wide range of alkenes were oxidized to aldehyde and ketone products with anti-Markovnikov selectivity and to acetonides when acetone was employed as a co-solvent. Mechanistic studies support that Lewis acid coordination to the 1,3,2-dioxazolidine intermediate results in a 1,2-shift to generate carbonyl derivatives and a nucleophilic substitution pathway for the formation of acetonides.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Alkene Oxidations and Hypothesis
Scheme 2
Scheme 2. Mechanistic Studies and Proposed Mechanism
Scheme 3
Scheme 3. Acetonide Scope and Mechanism
(A) Scope of acetonide formation promoted by photoexcited nitroarenes. See the Supporting Information for full experimental conditions. aIsolated as a diol. bWith 30 mol % Fe(OTf)2. (B) Generation and isolation of a seven-membered ring intermediate formed by nucleophilic attack of acetone on the dioxazolidine intermediate. (C) Proposed mechanism for the oxidation of alkenes to acetonides by photoexcited nitroarenes.
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References

    1. Ertl P.; Altmann E.; McKenna J. M. The Most Common Functional Groups in Bioactive Molecules and How Their Popularity Has Evolved over Time. J. Med. Chem. 2020, 63, 8408–8418. 10.1021/acs.jmedchem.0c00754. - DOI - PubMed
    1. Rajagopalan A.; Lara M.; Kroutil W. Oxidative Alkene Cleavage by Chemical and Enzymatic Methods. Adv. Syn. Catal. 2013, 355, 3321–3335. 10.1002/adsc.201300882. - DOI
    2. Campbell A. N.; Stahl S. S. Overcoming the “Oxidant Problem”: Strategies to Use O2 as the Oxidant in Organometallic C–H Oxidation Reactions Catalyzed by Pd (and Cu). Acc. Chem. Res. 2012, 45, 851–863. 10.1021/ar2002045. - DOI - PMC - PubMed
    3. Shi Z.; Zhang C.; Tang C.; Jiao N. Recent advances in transition-metal catalyzed reactions using molecular oxygen as the oxidant. Chem. Soc. Rev. 2012, 41, 3381–3430. 10.1039/c2cs15224j. - DOI - PubMed
    1. Smidt J.; Hafner W.; Jira R.; Sieber R.; Sedlmeier J.; Sabel A. The Oxidation of Olefins with Palladium Chloride Catalysts. Angew. Chem., Int. Ed. 1962, 1, 80–88. 10.1002/anie.196200801. - DOI
    2. Hu M.; Wu W.; Jiang H. Palladium-Catalyzed Oxidation Reactions of Alkenes with Green Oxidants. ChemSusChem 2019, 12, 2911–2935. 10.1002/cssc.201900397. - DOI - PubMed
    1. Schroeder M. Osmium tetraoxide cis hydroxylation of unsaturated substrates. Chem. Rev. 1980, 80, 187–213. 10.1021/cr60324a003. - DOI
    2. Kolb H. C.; Van Nieuwenhze M. S.; Sharpless K. B. Catalytic Asymmetric Dihydroxylation. Chem. Rev. 1994, 94, 2483–2547. 10.1021/cr00032a009. - DOI
    1. Tsuji J.; Nagashima H.; Nemoto H. A General Synthetic Method for the Preparation of Methyl Ketones from Terminal Olefins: 2-Decanone. Org. Synth. 1984, 62, 9–13. 10.15227/orgsyn.062.0009. - DOI

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