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Bispalladacycle-Catalyzed Michael Addition of In Situ Formed Azlactones to Enones

Authors

  • Dipl.-Chem. Manuel Weber,

    1. Institut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart (Germany), Fax: (+49) 711-685-54330
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  • Dr. Sascha Jautze,

    1. Institut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart (Germany), Fax: (+49) 711-685-54330
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  • Dr. Wolfgang Frey,

    1. Institut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart (Germany), Fax: (+49) 711-685-54330
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  • Prof. Dr. René Peters

    Corresponding author
    1. Institut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart (Germany), Fax: (+49) 711-685-54330
    • Institut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart (Germany), Fax: (+49) 711-685-54330
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Abstract

The development and further evolution of the first catalytic asymmetric conjugate additions of azlactones as activated amino acid derivatives to enones is described. Whereas the first-generation approach started from isolated azlactones, in the second-generation approach the azlactones could be generated in situ starting from racemic N-benzoylated amino acids. The third evolution stage could make use of racemic unprotected α-amino acids to directly form highly enantioenriched and diastereomerically pure masked quaternary amino acid products bearing an additional tertiary stereocenter. The step-economic transformations were accomplished by cooperative activation by using a robust planar chiral bis-Pd catalyst, a Brønsted acid (HOAc or BzOH; Ac=acetyl, Bz=benzoyl), and a Brønsted base (NaOAc). In particular the second- and third-generation approaches provide a rapid and divergent access to biologically interesting unnatural quaternary amino acid derivatives from inexpensive bulk chemicals. In that way highly enantioenriched acyclic α-amino acids, α-alkyl proline, and α-alkyl pyroglutamic acid derivatives could be prepared in diastereomerically pure form. In addition, a unique way is presented to prepare diastereomerically pure bicyclic dipeptides in just two steps from unprotected tertiary α-amino acids.

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