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

Authors

  • Filipe J. S. Duarte Dipl.-Chem.,

    1. REQUIMTE, CQFB, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal), Fax: (+351) 212-948-550
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  • Eurico J. Cabrita Prof. Dr.,

    1. REQUIMTE, CQFB, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal), Fax: (+351) 212-948-550
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  • Gernot Frenking Prof. Dr.,

    1. Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Strasse, 35032 Marburg (Germany)
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  • A. Gil Santos Prof. Dr.

    1. REQUIMTE, CQFB, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal), Fax: (+351) 212-948-550
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Abstract

A rationalization of stereoselectivity: The mechanisms of proline-catalyzed and imidazole-co-catalyzed intramolecular Baylis–Hillman reactions have been studied by using density functional theory methods. The computational data has allowed us to rationalize the experimental outcome, 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 (see scheme).

original image

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.

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