Cooperative nitroaldol reactions

Catalytic enantio- and diastereoselective nitroaldol reactions were explored by using designed guanidine-thiourea brfunctional organocatalysts like 15 (Figure 4.4) under mUd and operationally simple biphasic conditions. These catalytic asymmetric reactions have a broad substrate generality with respect to the variety of aldehydes and nitroalkanes [43]. 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. 

Sohtome, Y, Takemura, N., Takada, K.et al. (2007) Organocatalytic asymmetric nitroaldol reaction cooperative effects of guanidine and thiourea functional groups. Chemistry, an Asian Journal, 2, 1150-1160. 

Interfacially active guanidinium-thiourea bifunctional catalyst 190 catalyzes highly enantioselective nitroaldol reactions in the presence of an external base such as KOH in toluene/water biphasic conditions. Although the retro-nitroaldol reactions generally proceed under basic conditions, addition of KI inhibits the retro-process. A cooperative reaction mode between guanidinium and thiourea moieties is supported by experiments using structural variants of 190. A positive nonlinear effect is observed between the enantiomeric excess of 190 and the product 191. These results support the hypothesis that self-a egation of 190 is necessary for catalysis (Scheme 28.22) (96, 97). Catalyst 190 has been used in the synthesis of chiral tertiary alcohol products obtained in nitroaldol reactions of nitroalkanes and a-ketoesters [98],... 

Because of the weak interaction between the H" " site and immobilized tertiary amine group, both the acid site and the amine group can act as catalytically active species. On the other hand, a nonimmobilized tertiary amine, such as triethylamine, strongly adsorbed on the acid site and deactivated each other. Therefore, SA-NEtj showed much higher activity for the above-mentioned Michael reaction and cyano-ethoxycarbonylation. These reactions hardly occurred with only siHca-alumina or the tertiary amine. The catalytic reaction pathway including acid-base cooperative activation is shown in Scheme 1.10. Similar to the case of silica-alumina, Al-MCM-41 was also reported as a support, which can enhance the amine-catalyzed nitroaldol reaction [14]. 

Since silica is such a common support for immobilization, the effect of the weakly acidic silanol groups has been studied. A cooperative silanol effect is thought to improve the catalytic activity of mesoporous silica-supported amines in base-catalyzed reactions such as the nitroaldol (Henry) condensation [6, 7], Knoevenagel condensation [6, 8,9], and Michael addition [6]. Thus immobilizing amines onto supports with stronger acid groups could be expected to further increase the catalytic activity. 

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