Density Functional Study of Proline-Catalyzed Intramolecular Baylis-Hillman Reactions

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Abstract

The mechanisms of proline-catalyzed and imidazole-co-catalyzed intramolecular Baylis-Hillman reactions have been studied by using density functional theory methods at the B3LYP/6-31G(d,p) level of theory. A polarizable continuum model (PCM B3LYP/6-31 ++ G(d,p)//B3LYP/6-31G(d,p)) was used to describe solvent effects. Different reaction pathways were investigated, which indicated that water is an important catalyst in the imine/enamine conversion step in the absence of imidazole. When imidazole is used as a co-catalyst, water is still important in the imidazole addition step, but is not present in the Baylis-Hillman cyclization step. The computational data has allowed us to rationalize the experimental outcome of the intramolecular Baylis-Hillman reaction, validating some of the mechanistic steps proposed in the literature, as well as to propose new ones that considerably change and improve our understanding of the full reaction path.
Original languageUnknown
Pages (from-to)1734-1746
JournalChemistry-A European Journal
Volume15
Issue number7
Publication statusPublished - 1 Jan 2009

Keywords

    Cite this

    @article{73d773e0472f47c9aeec6903b775baf0,
    title = "Density Functional Study of Proline-Catalyzed Intramolecular Baylis-Hillman Reactions",
    abstract = "The mechanisms of proline-catalyzed and imidazole-co-catalyzed intramolecular Baylis-Hillman reactions have been studied by using density functional theory methods at the B3LYP/6-31G(d,p) level of theory. A polarizable continuum model (PCM B3LYP/6-31 ++ G(d,p)//B3LYP/6-31G(d,p)) was used to describe solvent effects. Different reaction pathways were investigated, which indicated that water is an important catalyst in the imine/enamine conversion step in the absence of imidazole. When imidazole is used as a co-catalyst, water is still important in the imidazole addition step, but is not present in the Baylis-Hillman cyclization step. The computational data has allowed us to rationalize the experimental outcome of the intramolecular Baylis-Hillman reaction, validating some of the mechanistic steps proposed in the literature, as well as to propose new ones that considerably change and improve our understanding of the full reaction path.",
    keywords = "asymmetric catalysis Baylis-Hillman reactions density functional calculations reaction mechanisms transition states asymmetric alpha-amination diels-alder reaction alpha, beta-unsaturated aldehydes secondary-amines aldol reactions enantioselective synthesis stereoselective-synthesis bioorganic approach mannich reactions domino reactions",
    author = "Santos, {Ant{\'o}nio Gil de Oliveira} and Cabrita, {Eurico Jos{\'e} da Silva}",
    year = "2009",
    month = "1",
    day = "1",
    language = "Unknown",
    volume = "15",
    pages = "1734--1746",
    journal = "Chemistry-A European Journal",
    issn = "0947-6539",
    publisher = "WILEY-V C H VERLAG GMBH",
    number = "7",

    }

    TY - JOUR

    T1 - Density Functional Study of Proline-Catalyzed Intramolecular Baylis-Hillman Reactions

    AU - Santos, António Gil de Oliveira

    AU - Cabrita, Eurico José da Silva

    PY - 2009/1/1

    Y1 - 2009/1/1

    N2 - The mechanisms of proline-catalyzed and imidazole-co-catalyzed intramolecular Baylis-Hillman reactions have been studied by using density functional theory methods at the B3LYP/6-31G(d,p) level of theory. A polarizable continuum model (PCM B3LYP/6-31 ++ G(d,p)//B3LYP/6-31G(d,p)) was used to describe solvent effects. Different reaction pathways were investigated, which indicated that water is an important catalyst in the imine/enamine conversion step in the absence of imidazole. When imidazole is used as a co-catalyst, water is still important in the imidazole addition step, but is not present in the Baylis-Hillman cyclization step. The computational data has allowed us to rationalize the experimental outcome of the intramolecular Baylis-Hillman reaction, validating some of the mechanistic steps proposed in the literature, as well as to propose new ones that considerably change and improve our understanding of the full reaction path.

    AB - The mechanisms of proline-catalyzed and imidazole-co-catalyzed intramolecular Baylis-Hillman reactions have been studied by using density functional theory methods at the B3LYP/6-31G(d,p) level of theory. A polarizable continuum model (PCM B3LYP/6-31 ++ G(d,p)//B3LYP/6-31G(d,p)) was used to describe solvent effects. Different reaction pathways were investigated, which indicated that water is an important catalyst in the imine/enamine conversion step in the absence of imidazole. When imidazole is used as a co-catalyst, water is still important in the imidazole addition step, but is not present in the Baylis-Hillman cyclization step. The computational data has allowed us to rationalize the experimental outcome of the intramolecular Baylis-Hillman reaction, validating some of the mechanistic steps proposed in the literature, as well as to propose new ones that considerably change and improve our understanding of the full reaction path.

    KW - asymmetric catalysis Baylis-Hillman reactions density functional calculations reaction mechanisms transition states asymmetric alpha-amination diels-alder reaction alpha

    KW - beta-unsaturated aldehydes secondary-amines aldol reactions enantioselective synthesis stereoselective-synthesis bioorganic approach mannich reactions domino reactions

    M3 - Article

    VL - 15

    SP - 1734

    EP - 1746

    JO - Chemistry-A European Journal

    JF - Chemistry-A European Journal

    SN - 0947-6539

    IS - 7

    ER -