Water organocatalytic reactions

Cyclopropanation of a,P-unsaturated aldehydes with diethyl bromomalonate, proceeding via a cascade Michael/a-alkylation process, was carried out in the presence of catalyst 100 in water to give compounds 112 (Figure 24.34). This is a case of an on water organocatalytic reaction. Indeed, organic solvents such as CHCI3 or THF gave comparable levels of stereoselectivities but lower yields with respect to water [126]. 

More recently, a fluorous organocatalyst has been used to perform selective Diels-Alder reactions of dienes with oc,(3-unsaturated aldehydes in acetonitrile-water. The chiral fluorous imidazolidinone catalyst can be recovered using fluorous silica (80-90% recovery efficiency) and reused. Figure 7.10. Further organocatalytic reactions are presented later in this chapter. 

The additives of water can serve as mechanistic probes and aid in obtaining true mechanistic understanding in some organocatalytic reactions [123]. The water is nucleophile in palladium-catalyzed oxidative carbo-hydroxylation of allene-substituted conjugated dienes [124]. This is an example of Pd- catalyzed oxidation leading to C -C bond formation in water with subsequent water attack on a (rr-allyl) palladium intermediate. The different effect of the water concentration on the intra- and extra-diol oxygenations of 3,5-di-tert-butylcatechol with O2, catalyzed by FeC in tetrahydrofuran-water indicates that the intermediates for two reactions are different (model for Catechol-2,3-dioxygenases) [125]. 

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. 

Organocatalytic reactions have been investigated using water in small (1-3 equiv.) or higher amounts. It was reported that the proUne-catalyzed reaction of acetone and 4-nitrobenzaldehyde tolerated a small amount of water (<4 vol.%) without affecting the enantiomeric excess of the aldol product However, increasing the amount of water (20 vol.%) severely compromised the enantioselectivity and decreased the rate of formation of the aldol product [5b]. 

A small amount of water has had a role in other organocatalytic reactions. The presence of 1 equiv. of water improved the yields while maintaining excellent stereoselectivity in the reaction between thiopyranone and aldehydes in DMF [8]. 

Reviews of organocatalytic reactions in water (a) Mase, N. and Barbas, C.F,... 

---