Pd-Catalyzed Carbonylative α-Arylation of Aryl Bromides: Scope and Mechanistic Studies

Authors

  • Dennis U. Nielsen,

    1. Center for Insoluble Protein Structures (inSPIN), Interdisciplinary Nanoscience Center (iNANO), Department of Chemistry Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C (Denmark)
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  • Dr. Camille Lescot,

    1. Center for Insoluble Protein Structures (inSPIN), Interdisciplinary Nanoscience Center (iNANO), Department of Chemistry Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C (Denmark)
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  • Dr. Thomas M. Gøgsig,

    Corresponding author
    1. Center for Insoluble Protein Structures (inSPIN), Interdisciplinary Nanoscience Center (iNANO), Department of Chemistry Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C (Denmark)
    • Thomas M. Gøgsig, Center for Insoluble Protein Structures (inSPIN), Interdisciplinary Nanoscience Center (iNANO), Department of Chemistry Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C (Denmark)

      Anders T. Lindhardt, Interdisciplinary Nanoscience Center (iNANO), Biological and Chemical Engineering, Department of Engineering, Aarhus University, Finlandsgade 22, 8200 Aarhus N (Denmark)

      Troels Skrydstrup, Center for Insoluble Protein Structures (inSPIN), Interdisciplinary Nanoscience Center (iNANO), Department of Chemistry Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C (Denmark)

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  • Dr. Anders T. Lindhardt,

    Corresponding author
    1. Interdisciplinary Nanoscience Center (iNANO), Biological and Chemical Engineering, Department of Engineering, Aarhus University, Finlandsgade 22, 8200 Aarhus N (Denmark)
    • Thomas M. Gøgsig, Center for Insoluble Protein Structures (inSPIN), Interdisciplinary Nanoscience Center (iNANO), Department of Chemistry Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C (Denmark)

      Anders T. Lindhardt, Interdisciplinary Nanoscience Center (iNANO), Biological and Chemical Engineering, Department of Engineering, Aarhus University, Finlandsgade 22, 8200 Aarhus N (Denmark)

      Troels Skrydstrup, Center for Insoluble Protein Structures (inSPIN), Interdisciplinary Nanoscience Center (iNANO), Department of Chemistry Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C (Denmark)

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  • Dr. Troels Skrydstrup

    Corresponding author
    1. Center for Insoluble Protein Structures (inSPIN), Interdisciplinary Nanoscience Center (iNANO), Department of Chemistry Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C (Denmark)
    • Thomas M. Gøgsig, Center for Insoluble Protein Structures (inSPIN), Interdisciplinary Nanoscience Center (iNANO), Department of Chemistry Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C (Denmark)

      Anders T. Lindhardt, Interdisciplinary Nanoscience Center (iNANO), Biological and Chemical Engineering, Department of Engineering, Aarhus University, Finlandsgade 22, 8200 Aarhus N (Denmark)

      Troels Skrydstrup, Center for Insoluble Protein Structures (inSPIN), Interdisciplinary Nanoscience Center (iNANO), Department of Chemistry Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C (Denmark)

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Abstract

Reaction conditions for the three-component synthesis of aryl 1,3-diketones are reported applying the palladium-catalyzed carbonylative α-arylation of ketones with aryl bromides. The optimal conditions were found by using a catalytic system derived from [Pd(dba)2] (dba=dibenzylideneacetone) as the palladium source and 1,3-bis(diphenylphosphino)propane (DPPP) as the bidentate ligand. These transformations were run in the two-chamber reactor, COware, applying only 1.5 equivalents of carbon monoxide generated from the CO-releasing compound, 9-methylfluorene-9-carbonyl chloride (COgen). The methodology proved adaptable to a wide variety of aryl and heteroaryl bromides leading to a diverse range of aryl 1,3-diketones. A mechanistic investigation of this transformation relying on 31P and 13C NMR spectroscopy was undertaken to determine the possible catalytic pathway. Our results revealed that the combination of [Pd(dba)2] and DPPP was only reactive towards 4-bromoanisole in the presence of the sodium enolate of propiophenone suggesting that a [Pd(dppp)(enolate)] anion was initially generated before the oxidative-addition step. Subsequent CO insertion into an [Pd(Ar)(dppp)(enolate)] species provided the 1,3-diketone. These results indicate that a catalytic cycle, different from the classical carbonylation mechanism proposed by Heck, is operating. To investigate the effect of the dba ligand, the Pd0 precursor, [Pd(η3-1-PhC3H4)(η5-C5H5)], was examined. In the presence of DPPP, and in contrast to [Pd(dba)2], its oxidative addition with 4-bromoanisole occurred smoothly providing the [PdBr(Ar)(dppp)] complex. After treatment with CO, the acyl complex [Pd(CO)Br(Ar)(dppp)] was generated, however, its treatment with the sodium enolate led exclusively to the acylated enol in high yield. Nevertheless, the carbonylative α-arylation of 4-bromoanisole with either catalytic or stoichiometric [Pd(η3-1-PhC3H4)(η5-C5H5)] over a short reaction time, led to the 1,3-diketone product. Because none of the acylated enol was detected, this implied that a similar mechanistic pathway is operating as that observed for the same transformation with [Pd(dba)2] as the Pd source.

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