Asymmetric Organocatalysis under Ultrasound Irradiation

The same group also investigated a self-Mannich reaction of aliphatic aldehyde (propanal) with p-anisidine under ultrasonic conditions (1 h) [54]. After subsequent reduction with sodium borohydride the corresponding aminoalcohol was obtained with good yield (80%) and selectivity (95 5 dr, 91% ee). In this case it is difficult to evaluate the effect of ultrasound because no comparative studies under conventional conditions were reported. 

In conclusion, microwave irradiation can be a useful tool for accelerating asymmetric organocatalytic reactions, especially with a higher-temperature tolerance. However, for several reactions presented in this section similar or almost identical results in terms of yield and enantioselectivity were obtained with conventional heating at the same temperature. There are also examples where under microwave conditions an increase in yield and/or enantioselectivity were observed. Unfortunately, because of relatively Uttle exploration of this area, it is still hard to speak about specific or non-thermal microwave effects. Therefore, in-depth mechanistic studies are required. 

The first examples of asymmetric organocatalytic reactions accelerated by ultrasound irradiation concern the application in phase-transfer catalysis. In 1995, 

Mirza-Aghayan et al. [51] reported a heterogeneous Michael addition of N-acetylaminomalonate to chalcone, in the presence of a chiral phase-transfer catalyst (N-benzyl-N-methylephedrinium bromide) and potassium hydroxide. The reaction was realized in toluene as well as in the absence of the solvent The authors observed that sonication enhances the rate of the reaction by 4—5 times with no loss of enantioselectivity compared to conventional stirring. For the reaction carried out without solvent at 60 °C for 5 min the product was isolated in 82% yield and 40% ee. This phenomenon is connected to homogenization of the reaction mixture and mass transfer enhancement. 

Sonochemical activation can strongly improve a wide range of chemical transformations however, the influence of ultrasound on asymmetric organocatalytic reactions is still a very weakly explored area. Based on reported ejamples it could be a very attractive and useful technique for accelerating organocatalytic reactions in heterogeneous systems (e.g., phase-transfer catalysis or reaction with sohd substrates on water). Evaluation of the usefidness of ultrasound in homogenous systems (e.g., in enamine activation) is still difficult and this topic requires more systematic studies in the future. 

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