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

• Published in: Chemistry, an Asian journal an Asian journal, 2007-09, Vol.2 (9), p.1150-1160
• Main Authors: Sohtome, Yoshihiro, Takemura, Nobuko, Takada, Keisuke, Takagi, Rika, Iguchi, Toshitsugu, Nagasawa, Kazuo
• Format: Article
• Language: English
• Subjects: Aldehydes - chemistry; Catalysis; chemoselectivity; Chromatography, Liquid; guanidine; Guanidine - chemistry; Magnetic Resonance Spectroscopy; nitroaldol reaction; organocatalysis; surfactants; Thiourea - chemistry
• ISSN: 1861-4728; 1861-471X
• DOI: 10.1002/asia.200700145

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. Helping each other: The guanidine–thiourea heterobifunctional compound 1 catalyzes diastereo‐ and enantioselective nitroaldol reactions at a chiral reaction interface. Addition of KI is crucial for inhibiting the retro‐nitroaldol reaction and achieving high asymmetric induction. Bn=benzyl.