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Organocatalytic Asymmetric Nitroaldol Reaction: Cooperative Effects of Guanidine and Thiourea Functional Groups

Authors

  • Yoshihiro Sohtome Dr.,

    1. Graduate School of Pharmaceutical Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
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  • Nobuko Takemura,

    1. Department of Biotechnology and Life Science, Faculty of Technology, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588, Japan, Fax: (+81) 42-388-7295
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  • Keisuke Takada,

    1. Department of Biotechnology and Life Science, Faculty of Technology, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588, Japan, Fax: (+81) 42-388-7295
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  • Rika Takagi,

    1. Department of Biotechnology and Life Science, Faculty of Technology, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588, Japan, Fax: (+81) 42-388-7295
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  • Toshitsugu Iguchi,

    1. Department of Biotechnology and Life Science, Faculty of Technology, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588, Japan, Fax: (+81) 42-388-7295
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  • Kazuo Nagasawa Prof. Dr.

    1. Department of Biotechnology and Life Science, Faculty of Technology, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588, Japan, Fax: (+81) 42-388-7295
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Abstract

Catalytic enantio- and diastereoselective nitroaldol reactions were explored by using designed guanidine–thiourea bifunctional organocatalysts under mild and operationally simple biphasic conditions. These catalytic asymmetric reactions have a broad substrate generality with respect to the variety of aldehydes and nitroalkanes. Based on this catalytic nitroaldol process, straightforward syntheses of cytoxazone and 4-epi-cytoxazone were achieved. These catalytic nitroaldol reactions require KI as an additive for highly asymmetric induction; it operates by inhibiting the retro mode of the reaction. On the basis of studies of structure and catalytic-activity relationships, a plausible guanidine–thiourea cooperative mechanism and a transition state of the catalytic reactions are proposed. Drastic substituent effects on the catalytic properties of this catalyst may lead to the development of new chiral surfactants.

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