Calix[4]arene Mediated Catalysis Under “On-water Conditions”: Hydrophobic Amplification of Weak Hydrogen-Bonds

In the last thirty years, calixarene macrocycles have gradually gained a special role in a wide range of supramolecular applications. At this regard, many efforts have been devoted to the design and synthesis of calixarene derivatives as catalysts for organic reactions , and among them the development of environmentally-oriented catalytic strategies has been particularly investigated. In a pioneering work, Sharpless introduced the expression "on-water conditions" to denote the rate acceleration observed in organic reactions when insoluble reactants are vigorously stirred in H2O suspension. Under "on-water conditions" the supramolecular affinities between reactants and catalyst play a key role. In fact, it is known that the hydrophobic effect forces the reactants and the catalyst to aggregate and thus amplifying the secondary interactions between them and favoring the molecular collisions. In the present communication, we will show that under “on-water conditions”, even weaker H-bond donor groups, such as amino-groups in 1 are effective to activate the substrate 2 in the Vinylogous Mukaiyama Aldol Reaction between 2 and 3 , on the basis of the hydrophobic amplification of H-bonds . Details on the catalytic efficiency of 1 and on the its recognition abilities toward the substrate 2 will be given.