Transition-Metal-Free Formal Sonogashira Coupling and α-Carbonyl Arylation Reactions

Authors

  • Birgit Prüger Dr.,

    1. Center for Catalysis, Department of Chemistry, Aarhus University, 8000 Aarhus C (Denmark), Fax: (+45) 8619-6199
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  • Gretchen E. Hofmeister Prof. Dr.,

    1. Center for Catalysis, Department of Chemistry, Aarhus University, 8000 Aarhus C (Denmark), Fax: (+45) 8619-6199
    2. Department of Chemistry, Carleton College, Northfield, MN 55057 (USA)
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  • Christian Borch Jacobsen,

    1. Center for Catalysis, Department of Chemistry, Aarhus University, 8000 Aarhus C (Denmark), Fax: (+45) 8619-6199
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  • David G. Alberg Prof. Dr.,

    1. Center for Catalysis, Department of Chemistry, Aarhus University, 8000 Aarhus C (Denmark), Fax: (+45) 8619-6199
    2. Department of Chemistry, Carleton College, Northfield, MN 55057 (USA)
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  • Martin Nielsen Dr.,

    1. Center for Catalysis, Department of Chemistry, Aarhus University, 8000 Aarhus C (Denmark), Fax: (+45) 8619-6199
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  • Karl Anker Jørgensen Prof. Dr.

    1. Center for Catalysis, Department of Chemistry, Aarhus University, 8000 Aarhus C (Denmark), Fax: (+45) 8619-6199
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Abstract

Transition-metal-free formal Sonogashira coupling and α-carbonyl arylation reactions have been developed. These transformations are based on the nucleophilic aromatic substitution (SNAr) of β-carbonyl sulfones to electron-deficient aryl fluorides, producing a key intermediate that, depending on the reaction conditions, gives the aromatic alkynes or α-aryl carbonyl compounds. The development of these reactions is presented and, based on investigations under basic and acidic conditions, mechanisms have been proposed. To develop the formal Sonogashira coupling further, a milder, two-step protocol is also disclosed that expands the reaction concept. The scope of these reactions is demonstrated for the synthesis of Sonogashira and α-carbonyl arylated products from a range of electron-deficient aryl fluorides with a variety of functional groups and aryl-, heteroaryl-, alkyl-, and alkoxy-substituted sulfone nucleophiles. These transition-metal-free reactions complement the metal-catalyzed versions in terms of substitution patterns, simplicity, and reaction conditions.

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